Archive for September, 2017

| Marlowe Hood |

PARIS (AFP) Lab monkeys with Parkinsons symptoms regained significant mobility after neurons made from human stem cells were inserted into their brains, researchers reported Wednesday in a study hailed as groundbreaking.

The promising results were presented as the last step before human clinical trials, perhaps as early as next year, the studys senior author, Jun Takahashi, a professor at Kyoto University, told AFP.

Parkinsons is a degenerative disease that erodes motor functions. Typical symptoms include shaking, rigidity and difficulty walking. In advanced stages, depression, anxiety and dementia are also common.

Worldwide, about 10 million people are afflicted with the disease, according to the Parkinsons Disease Foundation.

Earlier experiments had shown improvements in patients treated with stem cells taken from human foetal tissue and likewise coaxed into the dopamine-producing brain cells that are attacked by Parkinsons.

Dopamine is a naturally occurring chemical that plays several key roles in the brain and body.

But the use of foetal tissue is fraught with practical and ethical problems.

So Takahashi and his colleagues, in a medical first, substituted so-called induced pluripotent stem cells (iPSCs), which can be easily made from human skin or blood. Within a year, some monkeys who had could barely stand up gradually recovered mobility.

They became more active, moving more rapidly and more smoothly, Takahashi said by email. Animals that had taken to just sitting start walking around in the cage.

These findings are strong evidence that human iPSC-derived dopaminergic neurons can be clinically applicable to treat Parkinsons patients, he said.

Experts not involved in the research described the results as encouraging.

The treatment, if proven viable, has the potential to reverse Parkinsons by replacing the dopamine cells that have been lost a groundbreaking feat, said David Dexter, deputy research director at Parkinsons UK.

Not only did the new cells survive but they also integrated with the existing neuronal network, he said.

Neurons made from foetal tissue grafted into brains have been known to survive for more than a decade, and the researchers said they expected those derived from iPSCs to last just as long.

Tilo Kunath, Parkinsons Senior Research Fellow at the University of Edinburgh, said the outcome was extremely promising, and highlighted the advantage of avoiding stem cells extracted from human foetal tissue.

It means that this therapy can be used in any country worldwide, including Ireland and most of South America, where medical use of human embryonic stem cells is banned.

The results, reported in the journal Nature, were not the same for the dozen monkeys in the experiment, each of which received donor neurons from a different person.

Some were made with cells from healthy donors, while others were made from Parkinsons disease patients, said lead author Tetsuhiro Kikuchi, also from Kyoto University.

Read the rest here:
Study shows human stem cells restore mobility in Parkinson's monkeys - Borneo Bulletin Online

Biol Res 45: 279-287, 2012

RESEARCH ARTICLES

In Osteoporosis, differentiation of mesenchymal stem cells (MSCs) improves bone marrow adipogenesis

Ana Mara Pino1, Clifford J. Rosen2 and J. Pablo Rodrguez1*

1Laboratorio de Biologa Celular y Molecular, INTA, Universidad de Chile, 2Maine Medical Center Research Institute, Scarborough, Maine, USA.

ABSTRACT

The formation, maintenance, and repair of bone tissue involve close interlinks between two stem cell types housed in the bone marrow: the hematologic stem cell originating osteoclasts and mesenchymal stromal cells (MSCs) generating osteoblasts. In this review, we consider malfunctioning of MSCs as essential for osteoporosis. In osteoporosis, increased bone fragility and susceptibility to fractures result from increased osteoclastogenesis and insufficient osteoblastogenesis.

MSCs are the common precursors for both osteoblasts and adipocytes, among other cell types. MSCs' commitment towards either the osteoblast or adipocyte lineages depends on suitable regulatory factors activating lineage-specific transcriptional regulators. In osteoporosis, the reciprocal balance between the two differentiation pathways is altered, facilitating adipose accretion in bone marrow at the expense of osteoblast formation; suggesting that under this condition MSCs activity and their microenvironment may be disturbed. We summarize research on the properties of MSCs isolated from the bone marrow of control and osteoporotic post-menopausal women. Our observations indicate that intrinsic properties of MSCs are disturbed in osteoporosis. Moreover, we found that the regulatory conditions in the bone marrow fluid of control and osteoporotic patients are significantly different. These conclusions should be relevant for the use of MSCs in therapeutic applications.

Key words: MSCs, osteoporosis, adipogenesis, bone marrow microenvironment

BACKGROUND

The formation, maintenance, and repair of bone tissue depend on fine-tuned interlinks in the activities of cells derived from two stem cell types housed in the bone marrow interstice. A hematologic stem cell originates osteoclasts, whereas osteoblasts derive from mesenchymal stem cells (MSCs). Bone tissue is engaged in an unceasing process of remodelling through the turnover and replacement of the matrix: while osteoblasts deposit new bone matrix, osteoclasts degrade the old one.

Bone marrow provides an environment for maintaining bone homeostasis. The functional relationship among the different cells found in bone marrow generates a distinctive microenvironment via locally produced soluble factors, the extracellular matrix components, and systemic factors (Raisz, 2005; Sambrook and Cooper, 2006), allowing for autocrine, paracrine and endocrine activities. If only the main cellular components of the marrow stroma are considered, the activity of adipocytes, macrophages, fibroblasts, hematopoietic, endothelial and mesenchymal stem cells and their progeny bring about a complex range of signals.

Osteoporosis is a bone disease characterized by both decreased bone quality and mineral density. In postmenopausal osteoporosis, increased bone fragility and susceptibility to fractures result from increased osteoclastogenesis, inadequate osteoblastogenesis and altered bone microarchitecture.

The pathogenesis of the disease is hitherto unknown, hence the interest in basic and clinical research on the mechanisms involved (Raisz, 2005; Sambrook and Cooper, 2006). Cell studies on the origin of postmenopausal osteoporosis initially focused on osteoclastic activity and bone resorption processes; then on osteoblastogenesis, and more recently on the differentiation potential of mesenchymal stem cells (MSCs) (Shoback, 2007). Moreover, distinctive environmental bone marrow conditions appear to provide support for the development and maintenance of unbalanced bone formation and resorption (Nuttall and Gimble, 2004; Tontonoz et al., 1994). In this review, we consider the participation of the differentiation potential of MSCs, the activity of bone marrow adipocytes and the generation of a distinctive bone marrow microenvironment.

MESENCHYMAL STEM CELLS (MSCs)

Bone marrow contains stem-like cells that are precursors of nonhematopoietic tissues. These cells were initially referred to as plastic-adherent cells or colony forming-unit fibroblasts and subsequently as either mesenchymal stem cells or marrow stromal cells (MSCs) (Minguell et al., 2001; Lindnera et al., 2010; Kolf et al., 2007). There is much interest in these cells because of their ability to serve as a feeder layer for the growth of hematopoietic stem cells, their multipotentiality for differentiation, and their possible use for both cell and gene therapy (Minguell et al., 2001; Kolf et al., 2007). Friedenstein et al. (1970) initially isolated MSCs by their adherence to tissue culture surfaces, and essentially the same protocol has been used by other investigators. The isolated cells were shown to be multipotential in their ability to differentiate in culture or after implantation in vivo, giving rise to osteoblasts, chondrocytes, adipocytes, and/or myocytes.

MSCs populations in the bone marrow or those that are isolated and maintained in culture are not homogenous, but rather consist of a mixture of uncommitted, partially committed and committed progenitors exhibiting divergent stemness (Baksh et al., 2004). These heterogeneous precursor cells are morphologically similar to the multipotent mesenchymal stem cells, but differ in their gene transcription range (Baksh et al., 2004). It has been proposed that in such populations, cell proliferation, differentiation and maturation are in principle independent; stem cells divide without maturation, while cells close to functional competence may mature, but do not divide (Song et al., 2006).

Several molecular markers identify committed progenitors and the end-stage phenotypes, but at present there are no reliable cell markers to identify the uncommitted mesenchymal stem cells. Given the difficulty to identify a single marker to evaluate the population of stem cells, various combinations of these markers may be used (Seo et al., 2004; Lin et al., 2008; Xu et al., 2009). Therefore, MSCs are mainly defined in terms of their functional capabilities: self-renewal, multipotential differentiation and transdifferentiation (Baksh et al., 2004).

Hypothetically, the fate of MSCs appears to be determined during very early stages of cell differentiation ("commitment"). During this mostly unknown period, both intrinsic (genetic) and environmental (local and/or systemic) conditions interplay to outline the cell's fate towards one of the possible lineages. Based on microarray assays comparing gene expression at the stem state and throughout differentiation, it has been proposed that MSCs multilineage differentiation involves a selective mode of gene expression (Baksh et al., 2004; Song et al., 2006). It appears that "stemness" is characterized by promiscuous gene expression, where pluripotential differentiation results from the maintenance of thousands of genes at their intermediate expression levels. Upon commitment to one fate, only the few genes that are needed for differentiation towards the target tissue are selected for continuous expression, while the rest are downregulated (Zipori, 2005; Zipori, 2006).

The gene expression profile of undifferentiated human MSCs (h-MSCs) show high expression of several genes (Song et al., 2006; Tremain et al., 2001), but the contribution of such genes in preserving h-MSC properties, such as self-renewal and multilineage differentiation potential, or in regulating essential signalling pathways is largely unknown (Song et al., 2006). Several factors like age (Zhou et al., 2008), culture condition (Kultere et al., 2007), microenvironment (Kuhn and Tuan, 2010), mechanical strain (McBride et al., 2008) and some pathologies (Seebach et al., 2007; Hofer et al., 2010) appear to affect MSCs' intrinsic activity.

MSCs' commitment towards either the osteoblast or adipocyte lineage is determined by a combination of regulatory factors in the cells' microenvironment. The adequate combination leads to the activation of lineage-specific transcriptional regulators, including Runx2, Dlx5, and osterix for osteoblasts, and PPARy2 and a family of CAAT enhancer binding proteins for adipocytes (Murunganandan et al., 2009). Although the appropriate collection of regulatory factors required for suitable differentiation of MSCs is largely unknown, the TGF/BMPs, Wnt and IGF-I signals are briefly considered.

Several components of the BMP family are secreted in the MSCs' microenvironment (Lou et al., 1999, Gori et al., 1999; Gimble et al., 1995); BMP-2/4/6/7 have been identified as mediators for MSCs differentiation into osteoblasts or adipocytes (Muruganadan et al., 2009). The intracellular effects of BMPs are mediated by an interaction with cell surface BMP receptors (BMPRs type I and type II) (Gimble et al., 1995). It seems that differentiation into adipocytes or osteoblasts is highly dependent on the type of receptor I expressed by the cells, so that adipogenic differentiation requires signaling through BMPR IA, while osteogenic differentiation is dependent on BMPR IB activation (Gimble et al., 1995). The active receptors trigger the activation of Smad proteins, which induce specific genes. Under osteogenic differentiation, BMP action promotes osterix formation through Runx2-dependent and Runx2-independent pathways, thereby triggering osteogenic differentiation (Gori et al., 1999; Shapiro, 1999).

In addition to the role of BMPs in bone formation, BMPs also positively mediate the adipogenic differentiation pathways (Haiyan et al., 2009). It has been demonstrated that there is a binding site for Smad proteins in the promoter region of PPARy2 (Lecka-Czernik et al., 1999), and over-expression of Smad2 protein suppresses the expression of Runx2 (Li et al., 1998). These observations suggest that adequate content of osteoblasts and adipocytes in the bone marrow is dependent on balanced signaling through this pathway. Moreover, considering the distinct role assigned to BMPRIA and BMPRIB, the temporal gain or loss of a subtype of BMP receptors by MSCs could be critical for commitment and subsequent differentiation (Gimble et al., 1995144).

Wnt signaling in MSCs is also decisive for the reciprocal relationship among the osteo/adipogenic pathways. Activation of the Wnt/p-catenin pathway directs MSCs differentiation towards osteoblasts instead of adipocytes (Bennett et al., 2005; Ross et al., 2000; Moldes et al., 2003). Animal studies have shown that activation of the Wnt signaling pathway increases bone mass, preventing both hormone-dependent and age-induced bone loss (Bennett et al., 2005). Furthermore, Wnt activation may control cell commitment towards osteoblasts by blocking adipogenesis through the inhibition of the expression of both C/EBP and PPARy adipogenic transcription factors, as demonstrated in vivo in humans (Qiu et al., 2007), in transgenic mice expressing Wnt 10b (Bennett et al., 2005) and in vitro (Rawadi et al., 2003). MSCs' self-renewing and maintenance of the undifferentiated state appear to be dependent on appropriate canonical Wnt signaling, promoting increased proliferation and decreased apoptosis (Boland et al., 2004; Cho et al., 2006). The overexpression of LRP5, an essential co-receptor specifically involved in canonical Wnt signaling, has been reported to increase proliferation of MSCs (Krishnan et al., 2006). In addition, disruption in vivo or in vitro of -catenin signaling promoted spontaneous conversion of various cell types into adipocytes (Bennett et al., 2002). Moreover, the importance of this pathway for bone mineral density has been highlighted by the observation that genetic variations at either the LRP5 or Wnt10b gene locus are associated with osteoporosis (Brixen et al., 2007; Usui et al., 2007).

Also, insulin-like growth factor-I (IGF-I) signalling is clearly an important factor in skeletal development. The IGF regulatory system consists of IGFs (IGF-I and IGF-II), Type I and Type II IGF receptors, and regulatory proteins including IGF-binding proteins (IGFBP-1-6) and the acid-labile subunit (ALS) (Rosen et al., 1994). The ligands in this system (i.e. IGFs) are potent mitogens, and in some circumstances differentiation factors, that are bound in the circulation and interstitial fluid as binary (to IGFBPs) or ternary complexes (IGF-ALS-IGFBP-3 or -5) with little free IGF-I or -II. IGF bio-availability is regulated by the interaction of these molecules at the receptor level; hence changes in any component of the system will have profound effects on the biologic activity of the ligand. The IGFBPs have a particularly important role in regulating IGF-I access to its receptor, since their binding affinity exceeds that of the IGF receptors. The IGF system is unique because the IGFBPs are regulated in a cell-specific manner at the pericellular microenvironment, such that small changes in their concentrations could strongly influence the mitogenic activity of IGF-I (Jones and Clemmons, 1995; Hwa and Rosenfeld, 1999; Firth and Baxter, 2002). IGFs are expressed virtually by all tissues, and circulate in high concentrations. Although nearly 80% of the circulating IGF-I comes from hepatic sources, both bone and fat synthesize IGF-I and these tissues contribute to the total circulating pool. Locally produced IGF-I predominates over circulating IGF-I in maintaining skeletal integrity (Rosen et al., 1994; Kawai and Rosen, 2010), and both ALS and IGFBP-3 participate in regulating bone function. However, the possible autocrine/paracrine roles of IGF-I and IGFBPs in marrow (Liu et al., 1993; Peng et al., 2003) or in osteoblast (Zhao et al., 2000; Zhang et al., 2002; Wang et al., 2007) are practically unknown.

RELATIONSHIP BETWEEN THE OSTEO- / ADIPOGENESIS PROCESSES - THE FAT THEORY FOR OSTEOPOROSIS

Since in the bone marrow MSCs are the common precursor cells for osteoblast and adipocytes, adequate osteoblast formation requires diminished adipogenesis. As pointed out above, MSCs commitment and differentiation into a specific phenotype depends on hormonal and local factors (paracrine/autocrine) regulating the expression and/or activity of master differentiation genes (Nuttall and Gimble, 2004; Muruganadan et al., 2009) (Figure 1). A reciprocal relationship has been postulated to exist between the two differentiation pathways whose alteration would facilitate adipose accretion in the bone marrow, at the expense of osteoblast formation, thus decreasing bone mass (Reviewed in Rosen et, al 2009; Rodrguez et al.. 2008; Rosen and Bouxtein, 2006). Such unbalanced conditions prevail in the bone marrow of osteoporosis patients, upsetting MSC activity and the microenvironment (Nuttall and Gimble, 2004; Moerman et al., 2004; Rosen and Bouxtein, 2006). This proposition is known as the fat theory for osteoporosis. Moreover, this alteration of osteo-/adipogenic processes is also observed in other conditions characterized by bone loss, such as aging, immobilization, microgravity, ovariectomy, diabetes, and glucocorticoid or tiazolidindione treatments, highlighting the harmful consequence of marrow adipogenesis in osteogenic disorders (Wronski et al., 1986; Moerman et al., 2004; Zayzafon et al., 2004; Forsen et al., 1999).

Cell studies comparing the differentiation potential of MSCs derived from osteoporotic patients (o-MSCs) with that of control MSCs (c-MSCs) have shown unbalanced osteogenic/adipogenic processes, including increased adipose cell formation, counterbalanced by reduced production of osteogenic cells (Nuttall and Gimble, 2004; Rodrguez et al., 2008; Rosen and Bouxtein, 2006). Further research on MSC differentiation has shown that activation of PPARy2, a master transcription factor of adipogenic differentiation, positively regulates adipocyte differentiation while acting as a dominant negative regulator of osteogenic differentiation (Lecka-Czernik et al., 1999; Jeon et al., 2003; Khan and Abu-Amer, 2003). In contrast, an increase in bone mass density was observed in a PPARy deficient mice model; even the heterozygous deficient animals showed high bone mass and increased osteoblastogenesis (Cock et al., 2004). On the other hand, Runx2 expression by MSCs inhibits their differentiation into adipocytes, as may be concluded from experiments in Runx2-/- calvarial cells, which spontaneously differentiate into adipocytes (Kobayashi et al., 2000).

In vivo observations further support the fat theory. Early studies observed that osteoporosis was strongly associated with bone marrow adipogenesis. Iliac crest biopsies showed that bone marrow from osteoporotic patients had a considerable accumulation of adipocytes in relation to that of healthy elderly women (Moerman et al., 2004; Meunier et al., 1971). More recently, increased bone marrow adiposity measured by in vivo proton magnetic resonance (1H-MRS) has been associated with decreased bone mineral density in patients with low bone density (Griffith et al., 2005; Yeung et al., 2005; Blake et al., 2008).

In newborn mammals there is no marrow fat; however the number of adipocytes increases with age such that in humans over 30 years of age, most of the femoral cavity is occupied by adipose tissue (Moore and Dawson, 1990). The function of marrow fat is largely unknown; in humans it was first considered to be 'filler' for the void left by trabecular bone during aging or after radiation. Later, these cells have been proposed to have a role as an energy source, or as modulators of adjacent tissue by the production of paracrine, and autocrine factors (reviewed in Rosen et al., 2009). In fact, adipokines, steroids, and cytokines (Lee et al., 2002; Pino et al., 2010; Rosen et al., 2009;) can exert profound effects on neighboring marrow cells, sustaining or suppressing hematopoietic and osteogenic processes (Omatsu et al., 2010; Krings et al., 2012; Rosen et al., 2009; Rodrguez et al., 2008).

Thus, the function of bone marrow adipose tissue may be similar to that of extra medullary fat. As such, it has been well established that unbalanced production of signaling products from subcutaneous or visceral fat modulates several human conditions including obesity, lipodystrophy, atherogenesis, diabetes and inflammation. Recent studies in mice, suggest a complex fat phenotype in the bone marrow, presenting mixed brown and white adipose properties (Lecka-Czernik, 2012). Further work is needed to find out whether differences in the quality or quantity of marrow fat, take part in deregulated bone remodelling in some bone diseases.

STUDIES ON THE ACTIVITY OF OSTEOPOROTIC MSCs

Because of their ability to self-renew, human MSCs can be expanded and differentiated in vitro, offering many perspectives for tissue engineering and regenerative medicine approaches. However, there is scarce information on whether specific diseases affect the properties of MSCs, because of the difficult accessibility to human bone marrow in health and disease (Cipriani et al., 2011; Corey et al., 2007).

Our research has focused on the properties of MSCs isolated from bone marrow of control and osteoporotic post-menopausal women. We grouped our observations on functional characteristics of o-MSCs and c- MSCs in three categories, which are summarized in Table I, as follows:

General activities: h-MSCs isolated from osteoporotic and control donors have similar CFU-F, but different proliferation rates. O-MSCs showed significantly diminished proliferation rate and decreased mitogenic response to IGF-I. The pERK/ERK ratio is increased in o-MSCs, compared with control c-MSCs. In other cell types, activation of the MEK/ERK signalling pathway enhances the activity of adipogenic transcription factors (Prusty et al., 2002). We also observed decreased TGF- production by o-MSCs, as well as decreased capacity to generate and maintain a type I collagen-rich extracellular matrix, both conditions supporting cell differentiation into the adipocyte phenotype. Then, considering that the lineage fate of MSCs is dependent on early activation by specific BMPs, PPARy and Wnt signaling (Ross et al., 2000; Rawadi et al., 2003; Westendorf et al., 2004; Baron and Rawadi, 2007), we compared the expression level of some genes related to these pathways in c- and o- MSCs. Results obtained by RT-PCR showed that in c- and o-MSCs the expression level of mRNA for -catenin, Dkk-1, and BMPRIB was similar; while the level of mRNA for Wnt 3a was undetectable in both types of samples. The expression level of mRNA for GSK-3p, LRP6 and Osx was lower in o-MSCs than in c-MSCs, while the mRNA level for Ror2, Wnt 5a, BMPRIA showed doubtful. To further quantify the expression level of GSK-3P, LRP6, Osx, Ror2, Wnt 5a, BMPRIA real time RT-PCR was performed. As shown in Table I, statistically significant decreased mRNA levels for GSK-3p, LRP6 and Osx (0.64, 0.26 and 0.18 fold, respectively) were observed in o-MSCs, as compared to c-MSCs. In addition, mRNA levels for Ror2, Wnt 5a, and BMPRIA were similar in both types of cell samples.

These data suggest impaired regulation by the BMPs and Wnt pathways in o-MSCs, representing some intrinsic deviation from control cells that might underlie the impaired self-renewal, and adipogenic/osteogenic differentiation potential observed in o-MSCs. mRNA levels for Ror2, Wnt 5a, and BMPRIA were similar in both types of cell samples.

STUDIES ON THE ACTIVITY OF BONE MARROW FLUID OF POST-MENOPAUSAL WOMEN

Distinctive environmental bone marrow conditions appear to support the development and maintenance of the balance between bone resorption and bone formation. Knowledge is scarce about the intramedullar concentration of compounds with recognized regulatory effects on bone formation or resorption and is limited to some pathologic conditions or estimated from measurements in plasma (Wiig et al., 2004; Iversen and Wiig, 2005; Lee et al., 2002; Khosla et al., 1994).

Measurement of soluble molecules found in human bone marrow has been particularly difficult, not only because of tissue seclusion, but also because of the complicated anatomy and blood perfusion of bone. Since it may be expected that concentrations measured in the bone marrow fluid (BMF) more reliably reflect the physiologically relevant levels in the interstitial compartment surrounding the bone cells than values found in blood, we isolated the extracellular bone marrow fluid by directly spinning bone marrow samples for 20 min at 900xg. Considering the complex organization in such a regulatory milieu, we opted for evaluating some molecules recognized as markers of adipocyte, proinflammatory or osteoclastic/osteoblastic activity (Pino et al., 2010).

The concentrations of cytokines or receptors measured in the bone marrow extracellular fluid from control and osteoporotic human donors are indicated in Table II. In addition, the concentrations of IGF-I and its IGFBPs were analyzed, as well as the C-terminal telopeptide cross-links of type I collagen (CTX). Results summarized in Table II indicate significantly different concentrations of regulatory molecules in the extracellular fluid of control versus osteoporotic women; this last group was characterized by higher content of proinflammatory and adipogenic cytokines. Also, osteoporotic samples showed decreased leptin bioavailability, suggesting that insufficient leptin action may characterize the osteoporotic bone marrow (Pino et al., 2010). In addition, bioavailability of IGF-I appears diminished in o-BMF, as shown by the increased IGFBP3/IGF-I ratio.

TABLE II

Regulatory activity in bone marrow fluid of post-menopausal women

Taken together our results and those of other researchers identify significant differences between functional properties of control and osteoporotic MSCs, displayed in vitro, in cells under basal or differentiating conditions. Moreover, it can be concluded that such divergence prevails also in vivo, because the bone marrow fluid of osteoporotic patients characterizes by unfavourable content of several regulatory molecules. Therefore, the properties of both MSCs and bone marrow microenvironment are significantly impaired in osteoporotic patients, negatively affecting bone formation.

CONCLUSIONS

In the pathogenesis of osteoporosis, impairment of both MSCs functionality and microenvironment add to the known detrimental effect of increased osteoclast activity, resulting in decreased bone formation.

O-MSCs are characterized by intrinsic functional alteration leading to poor osteogenic capability and increased adipogenesis. Osteoporotic bone marrow microenvironment differs from the control microenvironment by increased concentration of pro-adipogenic and pro-inflammatory regulatory factors.

The content and/or quality of adipocytes in the bone marrow appear critical to delineate impairing of MSCs; in this sense osteoporosis could be homologated to other age-related diseases such as obesity, atherogenesis and diabetes, which are characterized by extramedullar unbalanced adipocyte formation and signaling.

Currently it is not known how damaged o-MSCs emerge, further work is needed to ascertain the role of the microenvironment, and genetic and epigenetic factors, as proposed for other stem cells-related pathologies.

The conclusion that intrinsic properties of MSCs are altered in osteoporosis should be relevant for the therapeutic use of MSCs, which represent an interesting promise for regenerative medicine for several severe human diseases.

The possibility of reversing o-MSCs impairment opens new perspectives for osteoporosis therapy.

ACKNOWLEDGEMENTS

We thank Dr. Mariana Cifuentes for her critical review of the manuscript and valuable comments. This work was supported by a grant from the Fondo Nacional de Ciencia y Tecnologa (FONDECYT # 1090093)

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KUHN NZ, TUAN RS (2010) Regulation of stemness and stem cell niche of mesenchymal stem cells: implications in tumorigenesis and metastasis. J Cell Physiol 222: 268-277. [Links]

KULTERE B, FRIEDL G, JANDROSITZ A, SNCHEZ-CABO F, PROKESCH A, PAAR C, SCHEIDELER M, WINDHAGER R, PREISEGGER KH, TRAJANOSKI Z (2007) Gene expression profiling of human mesenchymal stem cells derived from bone marrow during expansion and osteoblast differentiation. BMC Genomics 8: 70-84. [Links]

LECKA-CZERNK B (2012) Marrow fat metabolism is linked to the systemic energy metabolism. Bone 50: 534-539. [Links]

LECKA-CZERNIK B, GRINNELL SJ, MOERMAN EJ, CAO X, MANOLAGAS SC, OBRIEN CA (1999) Identification of a Smad binding element in the PPARy2 promoter: A potential site of cross-talk between osteoblastogenesis and adipogenesis signaling pathways. J Bone Miner Res 14: Suppl1, S1056. [Links]

LECKA-CZERNIK B, GUBRIJ I, MOERMAN EA, KAJKENOVA O, LIPSCHITZ DA, MANOLAGAS SC, JILKA RL (1999) Inhibition of Osf2/Cbaf1 expression and terminal osteoblast differentiation by PPAR-gamma2. J Cell Biochem 74: 357-371. [Links]

LEE WY, KANG MI, OH ES, HAN JH, CHA BY, LEE KW, SON HY, KANG SK, KIM CC. (2002) The role of cytokines in the changes in bone turnover following bone marrow transplantation. Osteoporos Int 13:62-68. [Links]

LI J, TSUJI K, KOMORI T, MIYAZONO K, WRANA JL, ITO Y, NIFUJI A, NODA M (1998) Smad2 overexpression enhances smad4 gene expression and suppresses Cbfa1 gene expression in osteoblastic osteosarcoma ROS17/2.8 cells and primary rat calvaria cells. J Biol Chem 273: 31009-31015. [Links]

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Read the original:
In Osteoporosis, differentiation of mesenchymal stem cells ...

Wed,17 Dec 2003 05:30:00

Bone marrow transplant is a procedure in which healthy bone marrow is transplanted into a patient whose bone marrow is not functioning properly. Problems in bone marrow are often caused by chemotherapy or radiation treatment for cancer. This procedure can also be done to correct hereditary blood diseases. The healthy bone marrow may be taken from the patient prior to chemotherapy or radiation treatment (autograft), or it may be taken from a donor (allograft).

Wed,17 Dec 2003 05:30:00

Bone marrow is the soft, sponge-like material found inside bones. It contains immature cells called stem cells that produce blood cells. There are three types of blood cells: white blood cells, which fight infection; red blood cells, which carry oxygen to and from organs and tissues; and platelets, which enable the blood to clot.

Wed,17 Dec 2003 05:30:00

Alternatively, hereditary or acquired disorders may cause abnormal blood cell production. In these cases, transplantation of healthy bone marrow may save a patient's life. Transplanted bone marrow will restore production of white blood cells, red blood cells, and platelets.

Wed,17 Dec 2003 05:30:00

Donated bone marrow must match the patient's tissue type. It can be taken from the patient, a living relative (usually a brother or a sister), or from an unrelated donor. Donors are matched through special blood tests called HLA tissue typing.

Bone marrow is taken from the donor in the operating room while one is unconscious and pain-free (under general anaesthesia). Some of the donor's bone marrow is removed from the top of the hip bone. The bone marrow is filtered, treated, and transplanted immediately or frozen and stored for later use. Then, transplant material is transfused into the patient through a vein and is naturally transported back into the bone cavities where it grows to replace the old bone marrow.

Alternatively, blood cell precursors, called stem cells, can be induced to move from the bone marrow to the blood stream using special medications. These stem cells can then be taken from the bloodstream through a procedure called leukapheresis.

The patient is prepared for transplantation by administering high doses of chemotherapy or radiation (conditioning). This serves two purposes. First, it destroys the patient's abnormal blood cells or cancer. Second, it inhibits the patient's immune response against the donor bone marrow (graft rejection).

Following conditioning, the patient is ready for bone marrow infusion. After infusion, it takes 10 to 20 days for the bone marrow to establish itself. During this time, the patient requires support with blood cell transfusions.

Wed,17 Dec 2003 05:30:00

Wed,17 Dec 2003 05:30:00

The major problem with bone marrow transplants (when the marrow comes from a donor, not the patient) is graft-versus-host disease. The transplanted healthy bone marrow cells may attack the patient's cells as though they were foreign organisms. In this case, drugs to suppress the immune system must be taken, but this also decreases the body's ability to fight infections.

Other significant problems with a bone marrow transplant are those of all major organ transplants - finding a donor and the cost. The donor is usually a sibling with compatible tissue. The more siblings the patient has, the more chances there are of finding a compatible donor.

Wed,17 Dec 2003 05:30:00

The patient will require attentive follow-up care for 2 to 3 months after discharge from the hospital. It may take 6 months to a year for the immune system to fully recover from this procedure.

See the article here:
Bone marrow transplant - Doctor NDTV

Scientific pioneer, superstar surgeon, miracle worker thats how Paolo Macchiarini was known for several years. Dressed in a white lab coat or in surgical scrubs, with his broad, handsome face and easy charm, he certainly looked the part. And fooled almost everyone.

Macchiarini shot to prominence back in 2008, when he created a new airway for Claudia Castillo, a young woman from Barcelona. He did this by chemically stripping away the cells of a windpipe taken from a deceased donor; he then seeded the bare scaffold with stem cells taken from Castillos own bone marrow. Castillo was soon back home, chasing after her kids. According to Macchiarini and his colleagues, her artificial organ was well on the way to looking and functioning liked a natural one. And because it was built from Castillos own cells, she didnt need to be on any risky immunosuppressant drugs.

This was Macchiarinis first big success. Countless news stories declared it a medical breakthrough. A life-saver and a game-changer. We now know that wasnt true. However, the serious complications that Castillo suffered were, for a long time, kept very quiet.

Meanwhile, Macchiarinis career soared. By 2011, he was working in Sweden at one of the worlds most prestigious medical universities, the Karolinska Institute, whose professors annually select the winner of the Nobel prize in physiology or medicine. There he reinvented his technique. Instead of stripping the cells from donor windpipes, Macchiarini had plastic scaffolds made to order. The first person to receive one of these was Andemariam Beyene, an Eritrean doctoral student in geology at the University of Iceland. His recovery put Macchiarini on the front page of the New York Times.

Macchiarini was turning the dream of regenerative medicine into a reality. This is how NBCs Meredith Vieira put it in her documentary about Macchiarini, appropriately called A Leap of Faith: Just imagine a world where any injured or diseased organ or body part you have is simply replaced by a new artificial one, literally manmade in the lab, just for you. This marvelous world was now within reach, thanks to Macchiarini.

Last year, however, the dream soured, exposing an ugly reality.

Macchiarini gave his regenerating windpipes to 17 or more patients worldwide. Most, including Andemariam Beyene, are now dead. Those few patients who are still alive including Castillo have survived in spite of the artificial windpipes they received.

In January 2016, Macchiarini received an extraordinary double dose of bad press. The first was a Vanity Fair article about his affair with Benita Alexander, an award-winning producer for NBC News. She met Macchiarini while producing A Leap of Faith and was soon breaking one of the cardinal rules of journalism: dont fall in love with the subject of your story.

By the time the program aired, in mid-2014, the couple were planning their marriage. It would be a star-studded event. Macchiarini had often boasted to Alexander of his famous friends. Now they were on the wedding guest list: the Obamas, the Clintons, Vladimir Putin, Nicolas Sarkozy and other world leaders. Andrea Bocelli was to sing at the ceremony. None other than Pope Francis would officiate, and his papal palace in Castel Gandolfo would serve as the venue. Thats what Macchiarini told his fiancee.

But as the big day approached, Alexander saw these plans unravel, and finally realised that her lover had lied about almost everything. The pope, the palace, the world leaders, the famous tenor they were all fantasies.

Likewise the whole idea of a wedding: Macchiarini was still married to his wife of 30 years.

Macchiarinis deceit was so outlandish, Vanity Fair sought the opinion of the Harvard professor Ronald Schouten, an expert on psychopaths, who gave this diagnosis-at-a-distance: Macchiarini is the extreme form of a con man. Hes clearly bright and has accomplishments, but he cant contain himself. Theres a void in his personality that he seems to want to fill by conning more and more people.

Which left a big, burning question in the air: if Macchiarini was a pathological liar in matters of love, what about his medical research? Was he conning his patients, his colleagues and the scientific community?

The answer came only a couple of weeks later, when Swedish television began broadcasting a three-part expos of Macchiarini and his work.

Called Experimenten (The Experiments), it argued convincingly that Macchiarinis artificial windpipes were not the life-saving wonders wed all been led to believe. On the contrary, they seemed to do more harm than good something that Macchiarini had for years concealed or downplayed in his scientific articles, press releases and interviews.

Faced with this public relations disaster, the Karolinska Institute immediately promised to investigate the allegations but then, within days, suddenly announced that Macchiarinis contract would not be extended.

Macchiarinis fall was swift, but troubling questions remain about why he was allowed to continue his experiments for so long. Some answers have emerged from the official inquiries into the Karolinska Institute and the Karolinska University hospital. They identified many problems with the way the twin organisations handled him.

Macchiarinis fame had won him well-placed backers. These included Harriet Wallberg, who was the vice-chancellor of the Karolinska Institute in 2010, when Macchiarini was recruited. She pushed through his appointment despite the fact that he had some very negative references and dubious claims on his rsum.

This set a dangerous example. It showed department heads and colleagues that they should give Macchiarini special treatment.

He could do pretty much as he pleased. In the first couple of years at Karolinska, he put plastic airways into three patients. Since this was radically new, Macchiarini and his colleagues should have tested it on animals first. They didnt.

Likewise, they didnt undertake a proper risk assessment of the procedure, nor did Macchiarinis team seek government permits for the plastic windpipes, stem cells, and chemical growth factors they used. They didnt even seek the approval of Stockholms ethical review board, which is based at Karolinska.

Though Macchiarini was in the public eye, he was able to sidestep the usual rules and regulations. Or rather, his celebrity status helped him do so. Karolinskas leadership expected big things from their superstar, things that would bring prestige and funding to the institute.

They also cited a loophole known as compassionate use. Macchiarini, they claimed, wasnt really doing clinical research. No, he was just caring for his patients who were, one and all, facing certain death with no other treatment options available and no time to waste. In such dire circumstances, new treatments can be tried as a last resort.

This argument didnt wash with those who later investigated the case. In their view, Macchiarini was certainly engaged in clinical research. Besides which, compassionate concerns dont override the basic principles of patient safety and informed consent. Macchiarini, meanwhile, said he did not accept the findings of the disciplinary board.

As it turned out, Macchiarinis patients werent all at deaths door at the time he treated them. Andemariam Beyene, for instance, had recurrent cancer of the windpipe but, aside from a cough, was still in good health. But even if his days had been numbered, this didnt necessarily justify what Macchiarini put him through.

Beyenes death two and a half years after the operation, caused by the failure of his artificial airway, was a grueling ordeal. According to Pierre Delaere, a professor of respiratory surgery at KU Leuven, Belgium, Macchiarinis experiments were bound to end badly. As he said in Experimenten: If I had the option of a synthetic trachea or a firing squad, Id choose the last option because it would be the least painful form of execution.

Delaere was one of the earliest and harshest critics of Macchiarinis engineered airways. Reports of their success always seemed like hot air to him. He could see no real evidence that the windpipe scaffolds were becoming living, functioning airways in which case, they were destined to fail. The only question was how long it would take weeks, months or a few years.

Delaeres damning criticisms appeared in major medical journals, including the Lancet, but werent taken seriously by Karolinskas leadership. Nor did they impress the institutes ethics council when Delaere lodged a formal complaint.

Support for Macchiarini remained strong, even as his patients began to die. In part, this is because the field of windpipe repair is a niche area. Few people at Karolinska, especially among those in power, knew enough about it to appreciate Delaeres claims. Also, in such a highly competitive environment, people are keen to show allegiance to their superiors and wary of criticising them. The official report into the matter dubbed this the bandwagon effect.

With Macchiarinis exploits endorsed by management and breathlessly reported in the media, it was all too easy to jump on that bandwagon.

And difficult to jump off. In early 2014, four Karolinska doctors defied the reigning culture of silence by complaining about Macchiarini. In their view, he was grossly misrepresenting his results and the health of his patients. An independent investigator agreed. But the vice-chancellor of Karolinska Institute, Anders Hamsten, wasnt bound by this judgement. He officially cleared Macchiarini of scientific misconduct, allowing merely that hed sometimes acted without due care.

For their efforts, the whistleblowers were punished. When Macchiarini accused one of them, Karl-Henrik Grinnemo, of stealing his work in a grant application, Hamsten found him guilty. As Grinnemo recalls, it nearly destroyed his career: I didnt receive any new grants. No one wanted to collaborate with me. We were doing good research, but it didnt matter I thought I was going to lose my lab, my staff everything.

This went on for three years until, just recently, Grinnemo was cleared of all wrongdoing.

The Macchiarini scandal claimed many of his powerful friends. The vice-chancellor, Anders Hamsten, resigned. So did Karolinskas dean of research. Likewise the secretary-general of the Nobel Committee. The university board was dismissed and even Harriet Wallberg, whod moved on to become the chancellor for all Swedish universities, lost her job.

Unfortunately, the scandal is much bigger than Karolinska, which accounts for only three of the patients who have received Macchiarinis regenerating windpipes.

The other patients were treated at hospitals in Barcelona, Florence, London, Moscow, Krasnodar, Chicago and Peoria. None of these institutions have faced the same kind of public scrutiny. None have been forced to hold full and independent inquiries. They should be.

If the sins of Karolinska have been committed elsewhere, it is partly because medical research facilities share a common milieu, which harbours common dangers. One of these is the hype surrounding stem cells.

Stem cell research is a hot field of science and, according to statistics, also a rather scandal-prone one. Articles in this area are retracted 2.4 times more often than the average for biomedicine, and over half of these retractions are due to fraud.

Does the heat of stem cell research the high levels of funding, prestige and media coverage it enjoys somehow encourage fraud? Thats what our experience of medical research leads us to suspect. While there isnt enough data to actually prove this, we do have some key indicators.

We have, for example, a growing list of scientific celebrities who have committed major stem cell fraud. There is South Koreas Hwang Woo-suk who, in 2004, falsely claimed to have created the first human embryonic stem cells by means of cloning. A few years ago, Japans Haruko Obokata pulled a similar con when she announced to the world a new and simple and fake method of turning ordinary body cells into stem cells.

Hwang, Obokata and Macchiarini were all attracted to the hottest regions of stem cell research, where hope for a medical breakthrough was greatest. In Macchiarinis case, the hope was that patients could be treated with stem cells taken from their own bone marrow.

Over the years, this possibility has generated great excitement and a huge amount of research. Yet, for the vast majority of such treatments, there is little solid evidence that they work. (The big exception is blood stem cell transplantation, which has been saving the lives of people with leukemia and other cancers of the blood for decades.)

Its enough to worry officials from the US Food and Drug Administration (FDA). They recently published an article in the New England Journal of Medicine admitting that stem cell research has mostly failed to live up to its therapeutic promise.

An alarmingly wide gap has grown between what we expect from stem cells and what they deliver. Each new scientific discovery brings a flood of stories about how it will revolutionise medicine one day soon. But that day is always postponed.

An unhappy result of this is the rise of pseudo-scientific therapies. Stem cell clinics have sprung up like weeds, offering to treat just about any ailment you can name. In place of clinical data, there are gushing testimonials. There are also plenty of desperate patients who believe because theyve been told countless times that stem cells are the cure, and who cannot wait any longer for mainstream medicine. They and their loved ones fall victim to false hope.

Scientists can also suffer from false hope. To some extent, they believed Macchiarini because he told them what they wanted to hear. You can see this in the speed with which his breakthroughs were accepted. Only four months after Macchiarini operated on Claudia Castillo, his results provisional but very positive were published online by the Lancet. Thereafter it was all over the news.

The popular press also has a lot to answer for. Its love of human interest stories makes it sympathetic to unproven therapies. As studies have shown, the media often casts a positive light on stem cell tourism, suggesting that the treatments are effective and the risks low. It did much the same for Macchiarinis windpipe replacements. A good example is the NBC documentary A Leap of Faith. Its fascinating to rewatch as a lesson on how not to report on medical science.

It is fitting that Macchiarinis career unravelled at the Karolinska Institute. As the home of the Nobel prize in physiology or medicine, one of its ambitions is to create scientific celebrities. Every year, it gives science a show-business makeover, picking out from the mass of medical researchers those individuals deserving of superstardom. The idea is that scientific progress is driven by the genius of a few.

Its a problematic idea with unfortunate side effects. A genius is a revolutionary by definition, a risk-taker and a law-breaker. Wasnt something of this idea behind the special treatment Karolinska gave Macchiarini? Surely, he got away with so much because he was considered an exception to the rules with more than a whiff of the Nobel about him. At any rate, some of his most powerful friends were themselves Nobel judges until, with his fall from grace, they fell too.

If there is a moral to this tale, its that we need to be wary of medical messiahs with their promises of salvation.

Read the rest here:
Dr Con Man: the rise and fall of a celebrity scientist who fooled almost everyone - The Guardian

On Monday, the U.S. Food and Drug Administration (FDA) announced that the agency is targeting clinics that offer unproven stem cell therapies, calling such offices "unscrupulous clinics" selling "so-called cures." The FDA seized materials from one clinic in California, and sent a warning letter to another in Florida.

The FDA will not allow deceitful actors to take advantage of vulnerable patients by purporting to have treatments or cures for serious diseases without any proof that they actually work," said FDA Commissioner Dr. Scott Gottlieb in a statement.

The agency announced that on Friday, Aug. 25th, U.S. Marshals seized five vials of a vaccine that is intended for people at a high risk for smallpox (for example, people in the military) from StemImmune Inc. in San Diego, California. The FDA says it learned that StemImmune was using the vaccines as well as stem cells from body fat to create an unapproved stem cell therapy. On its website, StemImmune says "The patients own (autologous, adult) stem cells, armed with potent anti-cancer payloads, function like a Trojan Horse, homing to tumors and cancer cells, undetected by the immune system." The stem cell treatment was injected into the tumors of cancer patients at the California Stem Cell Treatment Centers in Rancho Mirage and Beverly Hills, California.

MORE: Three People Are Nearly Blind After Getting a Stem Cell Treatment

The FDA also sent a warning later to U.S. Stem Cell Clinic in Sunrise, Florida. The company recently came under public scrutiny when a March report revealed that three people had severe damage to their vision one woman went blindafter they were given shots of what the company said were stem cells into their eyes during a study sponsored by the clinic. The FDA says that an inspection of U.S. Stem Cell Clinic revealed that the clinic was using stem cells to treat diseases like Parkinson's, amyotrophic lateral sclerosis (ALS), chronic obstructive pulmonary disease (COPD), heart disease and pulmonary fibrosis. According to the FDA, there are currently only a limited number of stem cell therapies approved by the agencyincluding ones involving bone marrow, for bone marrow transplants in cancer care, and cord blood for specific blood-related disorders. There are no approved stem cell treatments for other diseases.

The FDA says U.S. Stem Cell Clinic also attempted to interfere with the FDA's most recent inspection by refusing to allow FDA investigators to enter without an appointment, and denied the agency access to its employees. "Refusing to permit entry or FDA inspection is a violation of federal law," the FDA says.

Action by the FDA on clinics promoting unproven stem cell therapies is "a long time coming," says Sean Morrison, former president of the International Society for Stem Cell Research (ISSCR) and d irector of the Childrens Research Institute at UT Southwestern. "C linics are preying on the hopes of desperate patients claiming they can cure all manner of diseases with stem cells that have not been tested in clinical trials, and in some cases, are flat out impossible."

In the past, medical experts were concerned over Americans traveling to countries with less medical regulation for stem cell therapies, but Morrison says such clinics have been popping up stateside over the last five years. "It's not a few companies in the U.S. making claims about therapies with stem cells," says Morrison. "It's scores of companies. The problem has exploded in the U.S."

Morrison blames the lack of FDA crackdown in the past for the growing problem. "At some point people made the calculation that the FDA didnt seem to be enforcing these laws," he says. "The margins are huge. They charge people tens of thousands of dollars."

Since stem cell therapy is still an active and legitimate area of scientific research, it can be hard for Americans to figure out what is safe and effective and what is not. Even when it comes to clinical trials, the scientific soundness is murky. A July 2017 paper reported that 18 U.S. companies have registered "patient-sponsored" stem cell studies on ClinicalTrials.gov. That means that the patients receiving the treatment paid for them, which isn't the case in more legitimate studies. None of these were gold standard studies: meaning the people were not randomly assigned to receive the treatment or not, so the participants knew they were receiving the therapy that could bias the results. Only seven of the studies disclosed upfront that patients had to pay to join the study, and none revealed that the costs ranged from $5,000 to $15,000 a treatment, Wired reports.

While Morrison says he's glad the FDA has taken action, he says it's not enoughat least not yet. "The FDA has to show that there is really a sustained commitment to enforcement," he says. "When the FDA wasnt bringing actions against these companies, I think people thought this meant that it was a gray area and that they could get away with it."

Undoing that damage could be a long process, and one that Morrison says needs consistent attention by the agency. In a letter released on Monday, FDA commissioner Gottlieb said the agency is stepping up enforcement of stem cell therapies and regenerative medicine. "Ive directed the FDA to launch a new working group to pursue unscrupulous clinics through whatever legally enforceable means are necessary to protect the public health," said Gottlieb. Whether those efforts have an impact remains to be seen.

Originally posted here:
FDA Cracks Down on Stem Cell Clinics But Patients Are Still at Risk - TIME

In BriefResearchers have discovered that acute myeloid leukemia causes leaking from the bone marrow that interferes with chemotherapy delivery. If chemotherapy for AML can be used together with drugs to treat this problem, outcomes may improve dramatically.

Researchers have discovered that the most common form of acute leukemia which strikes adults, acute myeloid leukemia (AML), prevents chemotherapy from being delivered properly by causing bone marrow to leak blood. This means that, by using drugs developed to treat blood vessel and heart problems in concert with chemotherapy, AML might be much more treatable. In this study, these drugs reversed bone marrow leaks in tissue from mice and humans, and also boosted chemotherapy effects. Since these drugs are already in clinical trials for other applications, the team hopes that they may be approved for use in the treatment of AML patients soon.

We found that the cancer was damaging the walls of blood vessels responsible for delivering oxygen, nutrients, and chemotherapy. When we used drugs to stop the leaks in mice, we were able to kill the cancer using conventional chemotherapy, Diana Passaro, Francis Crick Institute researcher and first author of the paper,said in a press release.

The team studied the ways in which AML affects bone marrow by injecting healthy mice with bone marrow from AML patients to create AML mice. They then used intravital microscopy to compare the bone marrow of AML mice with healthy mice and observed pre-loaded fluorescent dyes leaking from the bone marrow blood vessels into the AML mice. Next, they discovered that the cells lining the blood vessels in AML mice were oxygen-starved, which led to increases in nitric oxide (NO), a muscle relaxant. They realized this was probably causing the leaking, and provided NO blockers to the AML mice which slowed leukemia progress and extended remission.

The team not only helped chemotherapy drugs to reach their targets more effectively, but they also found that NO blockers increased stem cells in the bone marrow. This might help healthy cells out-compete cancerous cells, and improve treatment outcomes. Finally, the researchers found that an inability to reduce NO levels and chemotherapy failure were related.

With an average lifetime risk of less than half of one percent among the general population, AML is relatively rare. This is in addition to the fact that AML is a disease that primarily affects older people; the average age of AML patients in the US is 67, and the disease is even rarer before the age of 45. Despite this rarity, however, TheAmerican Cancer Society estimates that there will be around 21,380 new cases of AML in the US in 2017, and about 10,590 deaths, almost all in adults.

This high death rate is linked to the character of this form of cancer, which is particularly aggressive. This is in large part due to chemotherapy resistance and relapse, fewer than 25 percent of patients survive longer than five years after diagnosis. However, if this research leads to a new regimen of combined drug therapy, these numbers may change.

The team is optimistic about their findings and hopes to start clinical trials soon. Weve uncovered a biological marker for this type of leukemia as well as a possible drug target, Francis Crick Institute Group Leader and paper senior author Dominique Bonnet said in the press release. The next step will be clinical trials to see if NO blockers can help AML patients as much as our pre-clinical experiments suggest.

More:
Chemo-Boosting Drug Discovered for Leukemia - Futurism - Futurism

From left to right: Richard Stone, a doctor at Dana-Farber Cancer Institute in Boston, poses with Peter Karalekas (center), 76, and Matthew Churitch, 22. Churitch donated stem cells to Karalekas two years ago, and he visited Dana-Farber with Karalekas earlier this summer. (Courtesy photo)

BOSTON -- After winding his way through Massachusetts, Connecticut, New Hampshire and Maine for 76 years, Peter Karalekas has a proclamation: He's a Southerner now.

He still lives in Kittery, Maine, just about an hour from the Lowell middle school where he taught for 21 years.

He has no plans to move.

Rather, Karalekas considers himself a Southerner because of his stem cells.

He never exactly felt all that sick.

Karalekas worked tirelessly for decades, first as a teacher and coach at the James S. Daley Middle School in Lowell and then as the owner of a half-dozen T-Bones restaurants across New Hampshire.

Even despite the 12-hour days, seven days a week, in the grind of the restaurant industry, Karalekas felt healthy and rarely fell ill.

Peter Karalekas, left, a 76-year-old former Lowellian, smiles during his first meeting with Matthew Churitch, 22, of Nashville, Tennessee, who helped save Karalekas life by donating stem cells. (Courtesy photo)

The two, who do not have children, moved to Kittery 17 years ago.

Everything started to change in 2014.

Karalekas recalls being "short-winded," but he had very few other symptoms when he was diagnosed with myelodysplastic syndrome, a rare type of cancer in which the bone marrow is damaged and cannot produce enough blood cells.

The prognosis was not good.

"They said the only thing that would save me was a stem cell transplant," Karalekas said. "Otherwise, I had a couple of months to live, because my cells were all dropping drastically.

He went onto a registry, hoping for a donor to pop up, but doctors told him it could take from six months to two years to find the right match. Even with a transplant, Karalekas said, his chances of success were "30 to 40 percent."

The call came four weeks later.

Matthew Churitch got his call quickly, too.

He joined the National Marrow Donor Program's Be the Match Registry in 2014, the summer between his freshman and sophomore years at Clemson University. His mother had been on the registry to donate for years. Churitch's decision was simple: When a friend was diagnosed with leukemia, he knew he should sign up, too.

He did the requisite cheek swab, unsure if he would ever even be contacted to donate. By the time he had finished the following semester, he got the call.

A match was found.

Churitch went through several more levels of testing and preparation to donate stem cells to a stranger. He went to Clemson's student health center to have blood drawn.

He returned to his native Nashville, Tennessee, going to a medical center 10 days in a row to receive shots in his stomach that would stimulate his bone marrow and prepare his cells for transplant.

He sat for eight hours, a needle in each arm as his stem cells were filtered out so they could be transferred to Boston.

"Getting the shots isn't fun," he said. "You're pretty sore afterward for a few weeks. But knowing that the person on the other end is in hundreds and hundreds times more pain than any donor would ever go through -- that kind of pushed me through."

Karalekas and Churitch first connected via an anonymous letter, per the transplant registry's rules, updating Churitch on Karalekas's lengthy, isolated recovery. They were able to speak directly after a year.

Churitch dialed Karalekas' number on a lengthy walk to class, took a deep breath and hit the call button. Moments later, both men were crying and laughing.

"That was really awesome, just being able to hear his voice and recognize that there's somebody else on the other end of this," Churitch said. "A lot of people don't get the chance to connect with their recipients or their donors."

Karalekas wanted more. He told his wife early on that he wanted to meet his "angel from heaven," so when Churitch graduated Clemson earlier this year, Karalekas paid to bring the 22-year-old and his mother to New England.

In late June, Karalekas and his wife pulled into a pickup lane at Logan International Airport in Boston.

"I got out of the car, I charged over, and I gave them both a huge hug," Karalekas said.

Karalekas showed Churitch and his mother around for five days.They went on a private tour of Fenway Park; they wandered the historic streets of Portsmouth, New Hampshire; they visited Dana-Farber together to meet the team that treated Karalekas.

Both families quickly bonded. Karalekas recalls his brother George asking Churitch about his portable phone charger, expressing curiosity about how convenient it was. A few weeks later, a brand-new portable charger arrived at George's door, a gift from Churitch.

In January, Karalekas and his wife will vacation in Arizona and will cheer on Churitch's mother -- without Churitch even present -- in the Phoenix Marathon.

Donor and recipient talk every week.

"It's like we're a very, very close-knit family now," Karalekas said. "He's the son we never had."

Churitch is now in his first year at the University of South Carolina School of Medicine Greenville with hopes of becoming a physician. He hopes to use Karalekas's experience as inspiration for any patients facing future hardship, and he hopes that others, especially young people, will see their success and join the registry.

"You never know where that will take you," he said. "You can gain a friend for life, impact somebody and their family in need."

Karalekas said he feels he has a new life: His chances of beating the disease are now 97 percent, he says, up from the 30 percent or 40 percent when he started treatment. Thanks to the transplant from a handsome, athletic college student in Tennessee.

"I said, 'I'm a Southerner now,'" Karalekas said. "My stem cells are 99 percent this gentleman. I'm 99 percent him."

Follow Chris on Twitter @ChrisLisinski.

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For Lowell native, stem cell match becomes a match as friends - Lowell Sun

AsianScientist (Aug. 30, 2017) - In a study published in Cell Stem Cell, scientists in Japan and Switzerland have found that bacterial infections can stress blood-producing stem cells in the bone marrow and reduce their ability to self-replicate.

When a person becomes infected with a virus or bacteria, immune cells in the blood or lymph react to the infection. Some of these immune cells use sensors on their surfaces, called Toll-like receptors (TLR), to distinguish invading pathogens from molecules that are expressed by the host. By doing so, they can attack and ultimately destroy pathogens thereby protecting the body without attacking host cells.

Bone marrow contains hematopoietic stem cells which create blood cells, such as lymphocytes and erythrocytes, throughout the lifetime of an individual. When infection occurs, a large number of immune cells are activated and consumed. Hence, it is necessary to replenish these immune cells by increasing blood production in bone marrow.

Recent studies have revealed that immune cells are not the only cells that detect the danger signals associated with infection. Hematopoietic stem cells also identify these signals and use them to adjust blood production. However, little was known about how hematopoietic stem cells respond to bacterial infection or how it affected their function.

In this study, researchers from Kumamoto University and the University of Zurich analyzed the role of TLRs in hematopoietic stem cells upon bacterial infection, given that both immune cells and hematopoietic stem cells have TLRs.

To generate a model of bacterial infection, researchers injected one of the key molecules found in the outer membrane of gram negative bacteria and known to cause sepsislipopolysaccharide (LPS)into lab mice. They then analyzed the detailed role of TLRs in hematopoietic stem cell regulation by combining genetically modified animals that do not have TLR and related molecules, or agents that inhibit these molecules.

The results showed that LPS spread throughout the body, with some eventually reaching the bone marrow. This stimulated the TLRs of the hematopoietic stem cells and induced them to proliferate. They also discovered that while LPS promoted stem cell proliferation, it also induced stressed the stem cells, impairing their ability to successfully self-replicate and resulting in diminished blood production. Similar results were obtained after infection with Escherichia coli bacteria.

Fortunately we were able to confirm that this molecular reaction can be inhibited by drugs, said Professor Hitoshi Takizawa of Kumamoto University who led the study. The medication maintains the production of blood and immune cells without weakening the immune reaction against pathogenic bacteria. It might be possible to simultaneously prevent blood diseases and many bacterial infections in the future.

The article can be found at: Takizawa et al. (2017) Pathogen-Induced TLR4-TRIF Innate Immune Signaling in Hematopoietic Stem Cells Promotes Proliferation but Reduces Competitive Fitness.

Source: Kumamoto University.Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Continued here:
Bacterial Infection Stresses Blood Stem Cells | Asian Scientist ... - Asian Scientist Magazine

Bone marrow contains hematopoetic stem cells, the precursors to every blood cell type. These cells spring into action following bone marrow transplants, bone marrow injury and during systemic infection, creating new blood cells, including immune cells, in a process known as hematopoiesis.

A new study led by University of Pennsylvania and Technical University of Dresden scientists has identified an important regulator of this process, a protein called Del-1. Targeting it, the researchers noted, could be an effective way to improve stem cell transplants for both donors and recipients. There may also be ways to modulate levels of Del-1 in patients with certain blood cancers to enhance immune cell production. The findings are reported this week in The Journal of Clinical Investigation.

Because the hematopoetic stem cell niche is so important for the creation of bone marrow and blood cells and because Del-1 is a soluble protein and is easily manipulated, one can see that it could be a target in many potential applications, said George Hajishengallis, the Thomas W. Evans Centennial Professor in the Department of Microbiology in Penns School of Dental Medicine and a senior author on the work.

I think that Del-1 represents a major regulator of the hematopoetic stem cell niche, said Triantafyllos Chavakis, co-senior author on the study and a professor at the Technical University of Dresden. It will be worthwhile to study its expression in the context of hematopoetic malignancy.

For Hajishengallis, the route to studying Del-1 in the bone marrow began in his field of dental medicine. Working with Chavakis, he had identified Del-1 as a potential drug target for gum disease after finding that it prevents inflammatory cells from moving into the gums.

Both scientists and their labs had discovered that Del-1 was also expressed in the bone marrow and began following up to see what its function was there.

In the beginning, I thought it would have a simple function, like regulating the exit of mature leukocytes [white blood cells]from the marrow into the periphery, Hajishengallis said, something analogous to what it was doing in the gingiva. But it turned out it had a much more important and global role than what I had imagined.

The researchers investigations revealed that Del-1 was expressed by at least three cell types in the bone marrow that support hematopoetic stem cells: endothelial cells, CAR cells and osteoblasts. Using mice deficient in Del-1, they found that the protein promotes proliferation and differentiation of hematopoetic stem cells, sending more of these progenitor cells down a path toward becoming myeloid cells, such as macrophages and neutrophils, rather than lymphocytes, such as T cells and B cells.

In bone marrow transplant experiments, the team discovered that the presence of Del-1 in recipient bone marrow is required for the transplanted stem cells to engraft in the recipient and to facilitate the process of myelopoesis, the production of myeloid cells.

When the researchers mimicked a systemic infection in mice, animals deficient in Del-1 were slower to begin making myeloid cells again compared to those with normal Del-1 levels.

We saw roles for Del-1 in both steady state and emergency conditions, Hajishengallis said.

Hajishengallis, Chavakis and their colleagues identified the protein on hematopoetic stem cells with which Del-1 interacts, the 3 integrin, perhaps pointing to a target for therapeutic interventions down the line.

The scientists see potential applications in bone marrow and stem cell transplants, for both donors and recipients. In donors, blocking the interaction between Del-1 and hematopoetic stem cells could enhance the mobilization of those progenitors into the bloodstream. This could be helpful for increasing donor cell numbers for transplantation. Transplant recipients, on the other hand, may need enhanced Del-1 interaction to ensure the transplanted cells engraft and begin making new blood cells more rapidly.

In addition, people undergoing chemotherapy who develop febrile neutropenia, associated with low levels of white blood cells, might benefit from the role of Del-1 in supporting the production of immune-related blood cells such as neutrophils.

Its easy to think of practical applications for these findings, said Hajishengallis. Now we need to find out whether it works in practice, so our studies continue.

Excerpt from:
Targeting bone marrow protein could be effective way to improve ... - Gears Of Biz

Scientists around the world are researching ways to reverse the aging process. There have been a few scientific breakthroughs in the last years, such as a March 2013, Science report. The report discussed how a team of scientists at the University of New South Wales had successfully reversed the aging process in mice with a NAD+ booster, NMN that stimulated the natural repair processes in cells (1).

In August 2017, a different technique was reported. According to ScienceDaily. its being touted as a possible fountain of youth. The ability to rejuvenate the heart and even reverse aging is the claim of a recent study (2).

The European Heart Journal published the study where researchers injected cardiac stem cells taken from the hearts of newborn lab rats into the hearts of old rats (22 months old, which is considered old for a rat lifespan). The result was a reversal in their aging hearts. The paper claims that the old rats appeared newly invigorated after receiving their injections.

In fact, the researchers noticed a 20% increase in the old rats exercising ability. Certainly, the scientists anticipated that this treatment would improve the old rats hearts, what they didnt expect were other benefits, such as the rat fur (shaved away for the surgery) growing back faster than normal.

In addition, the scientists noticed that the rats telomeres had changed. Instead shrinking, the common effect of aging, the telomers in the treated rats actually lengthened. This was an astounding side-effect of the cardiac stem cell injections.

Telomeres are repetitive nucleotide sequences that are found along the ends of chromosomes and become like protective caps. They prevent the ends of the chromosomes from deteriorating, as well as fusing with other chromosomes. Unfortunately, this protection begins to wear away with age and the length of the telomeres shorten as the body ages (3).To discover that the rats telomeres grew longer along with other systemic rejuvenating effects, the primary investigator on the research and director of the Cedars-Sinai Heart Institute Dr Eduardo Marbn proclaimed that it was like discovering, an unexpected fountain of youth.

Dr Marbns team completed the worlds first cardiac stem cell infusion in 2009. Dr Marbn developed the process of growing cardiac-derived stem cells when he was at John Hopkins University. Hes continued his research at Cedars-Sinai.

Conducting research in various heart-related cell therapy for more than 12 years, some of that research included using cardiosphere-derived cells.

According to Life Map Discovery, Cardiosphere-derived cells are isolated from atrial or ventricular biopsy specimens of patients undergoing heart surgery. The tissues are processed and cultured until a fibroblast-like cell layer forms. In this process, some cells migrate to this layer and techs can use them to further isolate and culture to create cardiospheres (4).

A March 2012 publication by the Journal of the American College of Cardiology (JACC) discussed the injection of cardiosphere-derived cells (CDCs) into infarcted mouse hearts. The injections resulted in superior improvement of cardiac function. (5)

According to Dr Marbn, Our previous lab studies and human clinical trials have shown promise in treating heart failure using cardiac stem cell infusions.

In the teams latest study, they used a specific type of stem cells taken from the newborn rats. Instead of stem cells, anther group received a placebo treatment consisting of saline injections. Each group was then compare to a group of four-month-old rats.

ScienceDaily reported that Dr Marbn stated that the cardiac stem cells secrete, tiny vesicles that are chock-full of signaling molecules such as RNA and proteins. Apparently, its the vesicles found in the young cells that, contain all the needed instructions to turn back the clock.

With these latest results, he said, Now we find that these specialized stem cells could turn out to reverse problems associated with aging of the heart.

The team is underway with more research, such as the ability to recreate the same results by administering the stem cells via IV (Intravenous) or with non-newborn cardiac stem cells. According to co-primary investigator and the first author of the study Lilian Grigorian-Shamagian, MD, PhD, their study didnt measure whether receiving the cardiosphere-derived cells extended lifespans. This will be another area the team plans to investigate.

References & Image Credits:(1) How NASA Anti-aging Drug Works(2) Science Daily(3) Wikipedia(4) LifeMapSC(5) OnlineJACC

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Cardiac Stem Cells May Be Fountain of Youth - Top Secret Writers

TAMPA (FOX 13) - Repairing a damaged heart has become much more than opening clogged arteries in the Cardiac Catheterization Lab at Pepin Heart Hospital in Tampa.

Dr. Charles Lambert and his team are injecting stem cells directly into specific areas in the walls of damaged hearts.

"We know where viable tissue is, what part of the heart is contracting and has live cells there," he explains.

Finding that living tissue begins with creating a color-coded map of the heart identifying areas where blood flow is maximized.

"We go back after mapping with a needle that comes out of the catheter and we do roughly twenty injections in viable tissue area," Lambert says.

It's all part of an experimental clinical trial Shiela Allen hopes will help her failing heart recover. Less than two hours after welcoming her youngest grandchild into this world, her grandson drove her to the emergency room.

"I couldn't breathe," she recalled.

Sheila was shocked when doctors told her that her heart was pumping at less than half of what it should.

"Now that I look back, I can figure out I had all the symptoms but I was just putting it off because I'm busy, I'm old, I'm a little bit overweight," she admits.

Like many women, Sheila ignored warning signs like fatigue, coughing and shortness of breath - especially when lying down.

"The coughing was odd to me because I was not congested, I could not lay flat in bed so I was propped up on four or five pillows," she says.

Similar to a balloon filled with too much water, the cardiac muscle is overstretched, thin, and weak. So weak, it can only pump a fraction of the blood inside its chambers to the rest of the body. That causes fluid to back up into the lungs and other parts of the body like the legs.

For about a decade, cardiologists have tried using stem cells to strengthen the muscle with mixed results. This study is hoping a new twist, will make it more successful.

Along with using the heart map to direct the injections, the stem cells are also different. Instead of taking them from the patient, syringes like these are filled with stem cells from donors.

"These trial cells are taken from healthy volunteers that are actually medical students, not here in town, but actually up in the northeast," he explains.

Another key difference in the study is the product's maker, Mesoblast. It is allowing people like Sheila, who have heart failure from unknown causes, to also enter the study. The clinical trial using the younger cells is now in 50 centers across the world.

"They're preserved so when we randomize a patient we take it off the shelf, treat it, warm it, the cells are perfectly alive and healthy and then administer it to the patients," Lambert says.

Side effects in earlier studies included a drop in blood pressure, bleeding, and fluid accumulation around the heart.

"It was basically like I was having another heart catheterization," Sheila says her side effects were minimal. "Three days after the procedure I was on a plane going on a trip."

She's not sure if she got a placebo or the actual cells, but as she completes her cardiac rehabilitation therapy, she says she is feeling better, "I've had a little more energy I dont know if it's related to that."

Energy allowing her to spend time with her family, and watch her youngest grandchild grow.

See original here:
Damaged hearts being repaired with stem cells - FOX 13 News, Tampa Bay

Stem cells and genome editing offer exciting opportunities within regenerative medicine. However, any clinical application of stem cells requires strict regulation to ensure that the cells are not exposed to animal derived products.

StemFit Basic02 is a xeno-free, defined medium for human pluripotent stem cell (hiPSC) culture that offers an effective solution for regenerative medicine research. This medium has been proven to effectively maintain Induced Pluripotent Stem (iPS) and Embryonic Stem (ES) cells under feeder-free conditions, during the reprogramming, expansion and differentiation phases of stem cell culture.

Specially formulated to enhance single cell expansion in the cloning step of stem cell genome editing, StemFit Basic02 offers superior and stable growth performance, high colony forming efficiency and robust scalable cell expansion. This ensures high karyotype stability over long periods and hence reproducible culture conditions.

StemFit cell culture media has been independently evaluated by CGT Catapult, an independent centre of excellence helping advance the UK cell and gene therapy industry. In these tests, StemFit not only delivered higher cell proliferation, but also showed characteristics such as homogeneity of gene expression compared with iPS cells cultured with 4 other media without any chromosomal abnormalities.

Original post:
Xeno-free Cell Culture Medium for Regenerative Medicine Research - Technology Networks

Stem cells and genome editing offer exciting opportunities within regenerative medicine.

However, any clinical application of stem cells requires strict regulation to ensure that the cells are not exposed to animal derived products.

Now Amsbio announces the availability of StemFit Basic02 feeder-free stem cell culture media.

StemFit Basic02 is a xeno-free, defined medium for human pluripotent stem cell (hiPSC) culture that offers an effective solution for regenerative medicine research.

This medium has been proven to effectively maintain Induced Pluripotent Stem (iPS) and Embryonic Stem (ES) cells under feeder-free conditions, during the reprogramming, expansion and differentiation phases of stem cell culture.

Specially formulated to enhance single cell expansion in the cloning step of stem cell genome editing, StemFit Basic02 offers superior and stable growth performance, high colony forming efficiency and robust scalable cell expansion.

This ensures high karyotype stability over long periods and hence reproducible culture conditions.

StemFit cell culture media has been independently evaluated by CGT Catapult, an independent centre of excellence helping advance the UK cell and gene therapy industry.

In these tests, StemFit not only delivered higher cell proliferation, but also showed characteristics such as homogeneity of gene expression compared with iPS cells cultured with four other media without any chromosomal abnormalities.

Read more from the original source:
Xeno-free cell culture medium for regenerative medicine research - Scientist Live

Photo: supplied

Obesity is a predominantly genetic disease, rather than a lifestyle choice thats the central premise of a new SBS show calledThe Obesity Myth.

The show, which followed doctors and patients at the University of Melbournes Austin Health forsix months, aimsto dispel the stigma attached to obesity.

Austin Healths Weight Control Clinic head professor Joseph Proietto says obese people face constant discrimination.

There is a lot of misunderstanding and misinformation about obesity in the community its an injustice, he says.Gluttony is seen as sinful, and to commit a sin you have to use free will. So the idea has been that people choose to be fat.

The world-renowned obesity management expert says he hopes the program will show obesity is far more complicated than generallythought.

Recent research has revealed how the body regulates weight through the hormones leptin (which decreases appetite) and ghrelin (which increases it). Whenpeople lose weight, their leptin levels decreaseand their ghrelin levels increase.

In 2011, Austin Health discovered levels of otherhormones also change according to weight gain or loss, and that those changes are enduring. Proiettosays this evidence points strongly to weight gain being genetic.

Finding that hormone changes after weight loss are long-lasting showed us that medication needs to be life-long, he says. Obesity is a chronic condition.

In 2014, another of the clinics studies showed the rate of weight loss did not affect how quickly weight was regained, and that more people succeeded in a rapid weight-loss program than a gradual program.

Professor Joseph Proietto. Photo: SBS

To combat obesity in patients, the clinics physicians conduct a thorough history and targeted examination, then offer a partial, very-low-energy diet thatreplaces breakfast and lunch.

After theyve lost all the weight they want to lose, whether it takes three months, six months or a year, then we wean them off the diet and back onto things like carbs and fruit, Proietto says.

A dietician will outlinea balanced, energy-reduced diet, and the clinic will continue to follow the patientsprogress. If theyre struggling to keep weight off because of increased hunger, medication is prescribed.

Proietto hopes the clinics research intoobesity will become common knowledge.

GPs are getting better at treating this condition than they used to be, he says. Hopefully they will continue to educate the public to try to dispel this myth.

If youre struggling with obesity Proietto says not to beat yourself around the head, because its probably genetic. He suggests seeking medical assistance.

Speak to your doctor about it, and see if you can get some help, he says.

View post:
SBS show The Obesity Myth is breaking down stigma - The Weekly Review

Every woman experiences the menopause differently, but many just aren't prepared for the range of symptoms and emotions this life shift can involve.

Oestrogen is the main hormone that reduces during the menopause. It affects many different areas of your body including your brain, so can cause many symptoms when its levels start to naturally fall. And these signs might occur even if you're still having periods. This time, called the perimenopause, can last for several years. It means many women won't make the connection to their hormones and end up suffering in silence.

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Dr Louise Newson, a GP who specialises in menopause (and runs a regular private menopause clinic at Parkway Hospital in Solihull), is passionate that this needs to change. She says she is often disappointed about how little accurate information there is for women to learn about the menopause. Which seems silly, considering it's something that's going to happen to all of them.

"Ten years ago if I'd had this conversation I would have said "oh, apart from night sweats and hot flushes, there's not that many other symptoms" but now I've seen hundreds and hundreds of women all telling me about all these other symptoms related to their changing hormone levels. And it's 2017 and many women are having rubbish lives because of it. And it doesn't have to be like this," she says.

Dr Newson wants women to know they're not alone. Here she explains the unexpected symptoms the menopause can cause:

It's often the symptoms people can't see that lead to the most difficulties, says Dr Newson.

Feelings of depression and low self-esteem, anxiety and panic attacks are very common symptoms of the menopause, she reveals. She has seen loads of women who have wrongly been prescribed antidepressants. Many also become fearful of everyday scenarios, she explains:

"I hear from a lot of women who find they're too scared to go into their car or they don't like their husband's driving anymore. They'll say they just worry about things they've never really worried about before."

Anxiety and depression symptoms can be debilitating and impact on work and family life. If you're experiencing anything similar, you should see your doctor.

Think the menopause will finally mean you're free from PMS? Not necessarily unfortunately, says Dr Newson. It's not uncommon for mood swings to appear during this time which can have a big impact on relationships.

"People tell me how cross they get - fed up with their children and fed up with their husbands. They often don't want their partner touching them. When women get better they realise how bad-tempered they've been and how hard it's been for their partner to live with them."

GettyThomas Barwick

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It might not be too surprising to learn that sleep becomes harder during perimenopause and menopause. Night sweats are common, of course. But even if you don't experience those, you might be more tired than normal and put it down to an exhausting life perhaps you have a stressful job, or grown up children giving you grief?

Dr Newson says if you can't get through the day without needing a nap, that's a sign you might need some help.

"A lot of people think they're tired because they have a new job or their children are stressing them out. I know myself when I was having symptoms I felt so tired and I just blamed it on work. And now I'm doing more work and I'm less tired! A lot of women tell me they literally come home from work and go straight to bed. Or they have a nap in the afternoon but they've never told anyone because they think it's just what happens when you get a bit older, which is awful," she says.

Falling oestrogen levels affect the joints in numerous ways making movement feel stiffer and more painful for some people. But many women will be misdiagnosed with arthritis when it's likely related to depleting hormones. It also means women are likely to stop exercising, even if they used to enjoy it before, potentially making other symptoms worse, says Dr Newson.

We're not very good at talking about bladders, but if you're going through the menopause or perimenopause, you might find you're getting up more frequently to pee in the night or even experiencing bladder weakness. Dr Newson explains it's because oestrogen affects the pelvic floor and bladder too.

"Often someone just wouldn't think to trouble the doctor because everyone knows your bladder gets a little bit weaker as you get older. And it's embarrassing if you cough and sneeze and get a little bit of wee in your pants. You likely wouldn't talk to your friends about it, even though your friends are probably suffering the same."

Dr Newson's advice is clear, if you're experiencing any of these symptoms, there are a range of treatment options, so make an appointment with your GP.

Dr Louise Newson has been working with Menopause & Me - a new website dedicated to supporting women throughout their menopause journeys.

Excerpt from:
5 unexpected symptoms of the menopause every woman needs to know about - Netdoctor

Chandigarh: For the first time, dairy farmers will now have the option of sexed semen for desi cattle breeds like Sahiwal, Gir and Red Sindhi cows and Murrah buffaloes. Sexed genetics, which is used to produce offspring of a desired sex, was not available for these breeds till now. ABS India (ABS), a division of Genus Plc, on Thursday launched 'sexed dairy genetics' in Chandigarh. The technology is designed to deliver more high-value pregnancies to dairy herds countrywide. Priced differently for different genetics, ABS Sexcel will be available to the Indian dairy farmers at approximately 30-40% less than the import price of the sexed semen. At a press conference to announce the launch, British deputy high commissioner, Andrew Ayre said, "It is an important day for the UK and the Indian dairy industry to extend Sexcel benefits to Indian dairy farmers, helping them to double their income by 2022 as targeted by the government." Arvind Gautam, managing director, ABS India said it would give farmers a new option for achieving their desired genetic blueprint and would help them profit through genetic progress. "We have a unique product and trial results are very effective. For the first time, sexed semen of indigenous cattle breeds like Sahiwal, Red Sindhi and Gir cows and Murrah buffaloes is available in India." Rahul Gupta, head (production) of the company added, "Dairy farmers may now breed their cows with the sexed genetics specifically designed to produce more female cows using this new technology. The technology produces female sexed semen through a new, cutting edge, laser-kill technology."

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Dairy farmers can get sexed semen for native cattle breeds within India - Times of India

By Giorgia GuglielmiAug. 31, 2017 , 2:13 PM

The saying you are what you eat is particularly true for female honey bees, which grow up to be either small, sterile workers or large, fertile queens depending on their diet. Previously, many researchers thought that something in the food fed to young queensa secretion called royal jellywas what made the difference. Now, a new study suggests its signaling molecules in the grub of young worker bees that keeps their sexual development in check. That diet, a mixture of pollen and honey called beebread, is shot through with a special kind of microRNA (miRNA), noncoding RNA molecules that help regulate gene expression. To find out whetherthese miRNAs were the culprit, scientists added them to the diet of larvae raised in the lab. These larvae developed more slowly, with smaller bodies and smaller ovaries than larvae fed food without the supplement, the team reports today in PLOS Genetics. The researchers also found that one common, plant-derived miRNA in beebread switches off a gene that helps larvae turn into queens. After being eaten with food, the miRNAs might enter the bees gut and spread throughout the rest of the body, where they could help regulate key genes, the scientists say. Although plant miRNAs alone arent likely to turn queens into workers, queens-to-be probably dont want to eat the commoners bread.

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Why some baby bees are destined to become workersor queens - Science Magazine

MANHATTAN, Kan. (AP) Research at the Kansas Wheat Innovation Center could revolutionize farming not just in Kansas but around the world.

Scientists there use advanced breeding techniques to isolate sought-after qualities. Different than genetic modification, breeding selects wheat varieties that need less water, can grow in extreme heat, or are durable against disease and pests in process that can take nearly a decade. Researchers at the Kansas Wheat Innovation Center hope to reduce that time so farmers can grow better wheat, faster, said Aaron Harries, vice president of research and operations.

This year, the wheat streak mosaic virus ravaged wheat crops in western Kansas. A tiny mite that remained active during an unusually warm winter spread the disease over a larger area than before. Within a few years, a variety of wheat resistant to the virus will be in the hands of farmers, Harries said.

But even as researchers develop tougher wheats, Mother Nature catches up. Disease evolves and climates change.

"We're always striving to improve the yield," he said.

This year, a consortium of international geneticists will likely finish sequencing wheat's genome.

Similar to the Human Genome Project that mapped human genetics, the project, which began in part with the center's research, will lay out the fundamentals of the wheat gene so scientists can more easily identify desirable traits.

It's not just farmers that benefit from Kansas Wheat research. Varieties are being developed that are naturally sweeter, so bakers and food companies can use less sugar to sweeten doughs.

The Capital-Journal reports that researchers are also talking to the growing number of people who have celiac disease. Those with the condition are unable to digest gluten, a protein found in wheat, barley and rye. With clues unlocked in the wheat genome, the institute hopes to locate the specific portions of the protein that cause the reaction and breed it out or silence it, Harries said.

"That's the protein that makes bread rise, so we're not trying to make it 'gluten free,'" he said. "We're trying to make it 'celiac safe.'"

To find the wheat qualities farmers and consumers want, researchers not only turn to wheat currently being grown, but they also have a store of ancient grains the wild grass varieties bred together to form modern wheat. Scientists collected the grains from places such as Syria, Iraq and Israel.

"We go treasure hunting for traits from those relatives and cross them into modern bread wheat," Harries said.

With all these different types of wheat on the market, Harries said the Kansas Wheat Innovation Center sees a revolution coming in the way wheat is grown, sold and processed. Currently, farmers growing consumer grain sell it to the elevator at harvest, which turns it over to a company in the food industry.

In future, farmers may contract directly with a certain company to grow a specific type of wheat.

A farmer with 100 acres may grow 50 acres of consumer wheat, 25 acres of sweet wheat and 25 acres of celiac-safe wheat, Harries said.

"Ultimately that will change the way we grow wheat." he said.

These advances in wheat are years away, but they begin in tiny pots in the institute's more than 35,000-square-foot, $11 million facility. That's where Heartland Plant Innovations research associate Tyler Suelter and a team breed new wheat varieties using a doubled haploid technique that can shave years off the breeding process.

Suelter said it sounds complex, but it's really an acceleration of traditional breeding.

The process involves producing plants that have all the same genetics. When a variety is identified, scientists emasculate the plants, leaving only the female reproductive system.

Maize is used to pollinate the plant so an embryo is produced. Since the embryo wasn't pollinated with wheat, it has half the number of chromosomes. Breeders will later double the count, so the plant has two copies of identical chromosomes a process that takes generations with typical breeding.

The research has produced nearly 100,000 doubled haploid variations and reduces the amount of time it takes to breed a new wheat variety.

"The time savings comes from how long it takes to grow the plants out. With (traditional breeding), you grow out several generations, and each takes six months," Suelter said. "With doubled haploid, you basically fix those traits in a single generation."

___

Information from: The Topeka (Kan.) Capital-Journal, http://www.cjonline.com

An AP Member Exchange shared by the Topeka Capital-Journal.

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Kansas researchers looking at new wheat varieties - San Francisco Chronicle

Women have had to face many challenges within the workforce, particularly in the agriculture sector, which has traditionally been dominated by men. This changing, however, as more women are establishing themselves as forces to be reckoned with within the industry.

Although in different parts of the business, both women are focused on making the company and industry more sustainable. Nkala started her career at McCain South Africa through the company Graduate Trainee Program in 2004. Since then she has been promoted into different positions including being the first ever female production manager at the Springs plant, a position she holds today. Vorster followed her interest and passion for genetics and extension to McCain South Africa, where she is currently the only female Agronomist.

Both women have pioneered different techniques and implemented strategies to help McCain South Africa become more sustainable as a business.

Pumeza Nkala

Educating colleagues and employees on water became incredibly important. By making people aware of the drought and its effect, we were able to ensure that water usage was handled effectively and efficiently, explains Nkala. The water reduction strategy looked at technical elements like water cascading, process refinements and different process technologies. The result of this is that each of the plants now has a dedicated water usage team that reviews water usage results daily and proposes gap closing measures.

Since implementing this strategy there has been a 42% reduction in water wastage at the Springs plant and a 23% reduction at the Delmas facility over the past two years.

Ineke Vorster

As an agronomist, she plays an important role within the business. She looks at how varieties can help to optimise yields on the field and in the factory. This is made possible when crops are planted in the correct place and in the correct way. If the soil isnt perfect or the conditions are not favourable there could be a negative impact on the crops and this, in turn, will affect stock and what consumers will be able to buy. Not only could this affect the business and consumers, but the farmers as well.

Vorster goes above and beyond to ensure that the farms are sustainable and that the landscape can handle the planting in order to preserve and look after the growing crops and farms. I absolutely love everything about my job, the trial work is quite repetitive and you need to constantly look for answers and solutions. By actively being out there in the fields, you pick up on things that can sometimes be missed in theory, says Vorster. She says that it is the interaction with farmers, field officers and trying to find a solution to problems that they are facing that really gives her a thrill.

Both Nkala and Vorster want to encourage young women to follow their dreams and to not let anything stand in their way. We have all faced challenges in our lives but it is how you overcome them and rise above them that really matters. If you love what you do and are following your passion every day it really does make a difference, so dont settle for anything less than what you want, concluded Vorster.

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Women forces to be reckoned with in agriculture - Bizcommunity.com

LONDON (Reuters)Scientists have successfully used reprogrammed stem cells to restore functioning brain cells in monkeys, raising hopes the technique could be used in future to help patients with Parkinsons disease.

Since Parkinsons is caused by a lack of dopamine made by brain cells, researchers have long hoped to use stem cells to restore normal production of the neurotransmitter chemical.

Now, for the first time, Japanese researchers have shown that human induced pluripotent stem cells (iPS) can be administered safely and effectively to treat primates with symptoms of the debilitating disease.

So-called iPS cells are made by removing mature cells from an individualoften from the skinand reprogramming them to behave like embryonic stem cells. They can then be coaxed into dopamine-producing brain cells.

The scientists from Kyoto University, a world-leader in iPS technology, said their experiment indicated that this approach could potentially be used for the clinical treatment of human patients with Parkinsons.

In addition to boosting dopamine production, the tests showed improved movement in affected monkeys and no tumors in their brains for at least two years.

The human iPS cells used in the experiment worked whether they came from healthy individuals or Parkinsons disease patients, the Japanese team reported in the journal Nature on Wednesday.

This is extremely promising research demonstrating that a safe and highly effective cell therapy for Parkinsons can be produced in the lab, said Tilo Kunath of the MRC Centre for Regenerative Medicine, University of Edinburgh, who was not involved in the research.

The next step will be to test the treatment in a first-in-human clinical trial, which Jun Takahashi of Kyoto University told Reuters he hoped to start by the end of 2018.

Any widespread use of the new therapy is still many years away, but the research has significantly reduced previous uncertainties about iPS-derived cell grafts.

The fact that this research uses iPS cells rather human embryonic stem cells means the treatment would be acceptable in countries such as Ireland and much of Latin America, where embryonic cells are banned.

Excitement about the promise of stem cells has led to hundreds of medical centers springing up around the world claiming to be able to repair damaged tissue in conditions such as multiple sclerosis and Parkinsons.

While some treatments for cancer and skin grafts have been approved by regulators, many other potential therapies are only in early-stage development, prompting a warning last month by health experts about the dangers of stem-cell tourism.

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Human Stem Cells Fight Parkinson's Disease in Monkeys - Scientific American

Evans applies a creamy layer of plant stem cells followed by an ultra-sound treatment, which pushes the nutrients into the skin 4,000 times deeper than they would reach by hand. Then the gloopy soothing mask which contains vitamins and minerals in an alginate base. It covers the eyes, nose and mouth before setting into rubbery contours for 20 minutes; Im feeling like the jelly inside a mould, setting for a party.

Just to ramp up the sci-fi element, Evans attaches galvanic currents at the top which make my forehead tingle and improve blood flow. It might feel a bit lonely behind the mask, but Evans is massaging my neck and shoulders, and Sandra Felicio, one of her colleagues, is suddenly at my feet, providing a reflexology treatment.

Once the mask is peeled off, theres still time for a facial massage with a copper wand for stress reduction and gentle face lifting, and an Intense Pulsed Light (IPL) PL laser treatment which stimulates collagen, evens out skin tone, and gets to work on pigmentation spots caused by sun damage. After 150 minutes of dedicated work, I now know how my car feels in the MOT garage.

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Is the 1k facial that helps you retain your summer glow worth it? - Telegraph.co.uk

Illustration by Sam Woolley/Gizmodo Media

As a young child, every morning at sunrise I would wake up to tap dance on the patio outside my moms bedroom door, much to my poor moms chagrin. These sunrise salutations became an enduring family story, as did my habit of getting up with the sun.Imagine my surprise, then, when a DNA test recently suggested that I am, in fact, a night owl.

This personal insight came to me via SlumberType, a new DNA analysis app that looks at 10 different genetic variants associated with sleep in order to model your genetic chronotype, or, as the company puts it, where you fall along a spectrum of morningness to eveningness. SlumberType is one of more than a dozen new DNA products in the new DNA app store recently launched by the consumer genetic testing startup Helix. The apps, which rely on DNA sequencing results the user purchases from Helix, range in purpose from the simply entertaining to those intended to helping people sleep, eat and exercise better. But as you might imagine, the secret to a good nights sleep is a little more complicated than DNA alone.

The idea behind SlumberType, Ron Andrews, the CEO of its parent company, Exploragen, told me, is to help people get a better nights sleep by understanding what genetics might say about their natural tendencies. The companys scientists combed through dozens of studies on sleep, and chose genetic variants most strongly associated with sleep to build a formula for modeling peoples individual chronotypes. Andrews said his test helped him realize that hes a bee, (a morning person) and adjust his sleep patterns accordingly. My own results had suggested I am at the far end of the spectrum, my peak activity hours falling in the wee hours of the night. I am typing these words, by the way, at 5:00 a.m., after falling asleep at my laptop working at the oh-so-late hour of 9:00 p.m.

In the past decade, DNA sequencing has gotten really, really cheap, paving the way for an onslaught of direct-to-consumer genetic testing companies that purport to offer the answers to everything from what wine you might like to the type of exercise optimized for your body.

Typically consumer DNA tests require that you spit in a tube, send your saliva into a lab, and a few weeks later get back a one-time report. Helix, though, has a different vision. For an initial fee of $80, the company sequences whats known as the exome, the 20,000 or so most important genes of the human genome. Its a far more extensive test than the genotyping companies like 23andMe and Ancestry.com perform. Customers can then pick and choose what pieces of information they might like from their genome, purchasing third-party DNA apps from the Helix store. These apps include those labeled entertainment, like Insitomes ancestry app designed to determine what percentage of your DNA is from Neanderthals. It includes health apps from partners like the Mayo Clinic to help inform people what genetic diseases they may carry. And it includes app advising people on lifestyle choices like exercise and nutrition, the category of testing that has received the most criticism from scientists. The idea is that customers will return to the DNA app store again and again throughout their lives.

Ive previously reported on the pseudoscientific nature of many lifestyle DNA tests. The premise easily inspires skepticisma simple spit test that tells you how to best live your life? Many tests rely on either incomplete science, or an incomplete understanding of how much your genetics relate to who you are.

But I was still curiouscould I glean something useful from these tests, something Id never considered? I tested out a handful of DNA wellness apps from Helixs app store, as well as from Orig3n, another consumer genetic testing company that offers lifestyle DNA tests. On the whole, I found myself besieged by so much (often conflicting) information that it was hard to make any sense of what it really meant. I was sold on the promises of unlocking a whole new level of information, for a truly personalized approach to my health, but what I unlocked instead was a data-driven headache.

One gene in Orig3ns Bliss test confirmedthat I am indeed a morning person, reassuring me that SlumberType had been wrong. Other tests contradicted facts I know to be true, such as the test that told me I have naturally high levels of B12; earlier this year, I started taking vitamin B supplements after a blood test at my doctors office revealed my levels of vitamin B were extremely low. Individual tests also seemed to sometimes contradict themselves, as did the test that informed me I was both not at risk for obesity (hooray!) and prone to obesity (damn) based on different genes.

One genetic variant suggested I may have lower levels of the bad kind of cholesterol. Another indicated higher cholesterol levels than the recommended levels. One test said I metabolized caffeine and alcohol normally. Another said I was fast to metabolize caffeine and slow to metabolize alcohol. While there seemed to be no agreement on whether I can taste bitterness in food, my taste buds assure me that I can.

In 2008, an European Journal of Human Geneticsarticlesuggested that direct-to-consumer genetic tests are often little better than horoscopes that tell people information they were already predisposed to believe. Like a horoscope, I found myself nodding along to information that already fit into my pre-conceived notion of self, and tossing aside anything that didnt.

Most of this stuff is bogus, Eric Topol, a geneticist at Scripps Research Institute, told me as he scrolled through Helixs DNA app store on the other end of the line. I can find hardly any science that backs most of this up. Its going to give genomics a bad name.

There are plenty of explanations for the inconstancies I found in my tests. In some cases, the science was simply shaky, based on studies that were too small, too few or too narrow to extrapolate for the general population. When it comes to nutrition, several experts told me that there is simply not enough research to back up the majority of the many nutrigenomics tests now on the market. (There are a few exceptions. For example, the genomics behind genes that result in lactose intolerance are well-studied.) Different tests look at different genes to tell you the same piece of information. And methods of interpretation vary. SlumberType, for example, built an algorithmic model of my chronotype based on several genetic variants. Orig3n, on the other hand, simply tells users about all of the individual genes they have and what each variant might mean, which is why some of the results seemed contradictory.

The other hitch is that we are, of course, more than the sum of our genetic partsmy tendency towards sunrise is based on more than just the As, Ts, Cs and Gs that comprise my DNA code. Children and elderly people generally rise early; teens stay up late at night. Gender, diet, ethnicity, exercise and other environmental factors can all play a role.

Ive been worried for many years that in the public discourse there is this message that we are our DNA, UC Berkeley geneticist Rasmus Nielsen told me. The biggest problem is that this stuff is marketed as actionable and there is no evidence of that. If theyre selling snake oil, its because of this implicit claim that you can somehow improve your health.

Test that give consumers information about disease must go through the FDA approval process, but otherwise consumer genetic testing has so far evaded regulatory approval. The biggest risk in getting a genetic palm reading is likely to your bank account. But critics point out other troubling possibilities. For one, the growing market of pseudoscientific tests might give consumers a misunderstanding of genetics.

The privacy you give up when giving out your genetic information is a concerna court of law could compel companies to hand over your DNA. And, as all genetic testing companies point out in their fine print, while the Genetic Information Non-Discrimination Act protects against health insurers requesting your genetic data, it does not prevent providers of life, disability or long-term care insurance from doing so when a test has already been done.

Nielsen also told me tests doling out fitness and dietary advice could wind up encouraging people to adopt lifestyle habits that are not really right for them. Many tests suggest that users seek out the advice of a doctor before making lifestyle changes, but often its in the fine print, or somewhere equally easy to miss.

Even if the information is useful, some studies have suggested consumers dont actually change their behavior based on genetic tests anyway.

Its hard to know if these tests are safe without knowing how people are really using them, said Neilsen. In general, you have to ask if its really good to have more information if you dont really have the skills to use that information?

For me, utility was the biggest sticking point. I had a deluge of data about my health and fitness, but there were so many data points I had no idea how to make sense of them. Some results were intriguing, such as the suggestion that a deleted GSTM1 gene means I need to eat more cruciferous vegetables to help my body make up for a lacking enzyme that helps with detoxification. Most of the time, though, the information just wasnt useful.

This isnt to say there are no genetic tests that are worthwhile. Tests like that for the BRCA gene, for example, can help a woman make important decisions about her own health, and parents-to-be often benefit from finding out whether they are carriers for serious genetic disorders.

Some of these things have value, said Topol, pointing to the hereditary cancer test set to debut in the Helix marketplace soon. But cholesterol, you dont need a genetic test for that. It doesnt matter if you have a gene variant. Either you have high cholesterol or you dont.

Robert Green, a Harvard geneticist and advisor to Helix, told me that while he doesnt think every DNA app on the market is useful or scientifically valid, he does think that the explosion of the consumer genomics market will help to educate consumers and ultimately to democratize DNA.

There is a tension between building on legitimate science and marketing things that stray so far from the science or imply lifestyle utility that hasnt been proven, he told me. There is an explosion going on in personalized genomics and its not going to slow down. I dont think we can stop it, so I think we have to start going in the other direction.

Green said he anticipates the field being messy for a while. In the end, though, he sees lifestyle products like those Helix and Orig3n offer as relatively harmless ways to start learning about genetics.

James Lu, co-founder and chief science officer of Helix, was upfront about the limitations of what his companys genetic testing can tell you.

Historically there has been this perspective that DNA is this book of all answers, a Magic 8 ball, per se, he said. Science has categorically proven thats untrue.

His hope, though, is that as the field progresses, the apps in the Helix app store will be able to do a better job contextualizing information to help consumers make sense of what all that data means.

Were going to have to merge DNA and other information together to provide complete answers, he said. Its still the early days. I think a lot of the problems we see in the field will resolve themselves.

Some of the products I tried did give me useful information about how to read my results. DNAFit offers several fitness and nutrition products through the Helix app store. When you get your results, before revealing them the company guides you to a page that explains everything about who we are is comprised of the interaction between two factors how we are born (our genetics), and what we do (our environment and lifestyle). Understanding your genetics, it says, can help you to change the second part and achieve a happier, healthier you.

In the end, though, information is only valuable if we can make sense of it.

DNAFits fine-print reveals something that reads closer to the truth: Genetic Information is subject to significant limitations; some of the interpretations that we provide may not be applicable;Genetic Information reported has not been clinically validated.

In the end, what use did learning I have genes that indicate I am a night owl really do? My genes are part of who I am. But who I am is not a night owl, no matter what any DNA test might say.

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I Tried a Bunch of DNA Tests and All I Got Was a Bunch of Useless Data - Gizmodo

To better manage patient health, healthcare systems are looking for innovative ways to managehealth risk.And to better manage patient health, NorthShore University HealthSystem is encouragingpatients to add a genetic test to their annual physical.

While NorthShore gauges patient interest in taking the test and helps patients choose what types of screening they may want, patients must pay for any testing themselves, according to an article in Business Insider. The hospital uses an algorithm that scans a patients EHR information to determine the appropriate tests. Because those tests tend to be relatively specific and the science behind the testing changes constantly, the hospital expects such testing to be done annually, rather than as a one-time screening.

As healthcare providers take on more risk for patient health in the context of value-based care, facilities like NorthShore feel a need to be more proactive about keeping patients healthy, rather than focusing solely on treating them when they become ill, Peter Hulick, M.D., the facilitys director of the Center for Personalized Medicine, told the publication

Some analysts have already dubbed the advent of consumer genetic testing a turning point for the practice of precision medicine, which uses genetic data to attempt to predict conditions to which patients may be prone, such as cancers that carry a known hereditary risk. Whether precision medicine warrants the positive buzz remains an open question, however, especially as labs responsible for genetic testing have come under scrutiny for aggressive marketing efforts and alleged kickback schemes.

Some of the questions surrounding the efficacy of genetic testing stem from the relative novelty of the field, so part of NorthShores mission in adding the tests lies in fleshing out the type of value such tests may have, according to the article.

Scientific data aside, the tests have been good for patient satisfaction, according to Hulick. He says offering the option of genetic testing has generated positive feedback, even among patients whose histories did not indicate a need to do any testing.

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NorthShore University HealthSystem now gives patients option for genetic testing during annual checkups - FierceHealthcare

Liverpool Womens Hospital is to expand its ability to genetically test newborn babies 12-fold.

The NHS Foundation Trust will be able to screen all infants for inherited conditions or illnesses and plan for early treatment as part of a major new IT project.

IT firm Novosco will introduce the computing system which also contribute to a major population health programme in Liverpool - analysing genetic information by location, identifying and enabling work to prevent localised health issues.

The role of genetics in healthcare is one of the most rapidly expanding areas of development for Liverpool Womens.

It provides a regional clinical genetics service covering a population of around 2.8 million people from across Merseyside, Cheshire and the Isle of Man.

Chief executive Kathryn Thomson posted on the trusts website: To discover that you or any child you have or plan to have may be at risk of a genetic disorder which could cause disability or a rare condition is traumatic.

People are sometimes shocked and anxious and wonder what the future might hold.

They need as much information and support as possible to help them cope.

That is why the often unsung work of our clinical genetics team is so important, providing diagnosis and supporting families when they need it most.

Novosco managing director Patrick McAliskey said: We are delighted to secure this contract which will enable the trust to take genetic testing to the next level and play an important role in the identification and prevention of conditions and illnesses in new-born babies and the wider population.

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Liverpool Women's Hospital to increase genetic testing of babies - Liverpool Echo

B. Bick, . Poindexter, UT Med. School/SPL

A depletion of brain cells that produce dopamine is responsible for the mobility problems seen in people with Parkinsons disease.

Japanese researchers report promising results from an experimental therapy for Parkinsons disease that involves implanting neurons made from reprogrammed stem cells into the brain. A trial conducted in monkeys with a version of the disease showed that the treatment improved their symptoms and seemed to be safe, according to a report published on 30 August in Nature1.

The studys key finding that the implanted cells survived in the brain for at least two years without causing any dangerous effects in the body provides a major boost to researchers hopes of testing stem-cell treatments for Parkinsons in humans, say scientists.

Jun Takahashi, a stem-cell scientist at Kyoto University in Japan who led the study, says that his team plans to begin transplanting neurons made from induced pluripotent stem (iPS) cells into people with Parkinsons in clinical trials soon.

The research is also likely to inform several other groups worldwide that are testing different approaches to treating Parkinsons using stem cells, with trials also slated to begin soon.

Nature breaks down the latest research and what it means for the future of stem-cell treatments.

Parkinsons is a neurodegenerative condition caused by the death of cells called dopaminergic neurons, which make a neurotransmitter called dopamine in certain areas of the brain. Because dopamine-producing brain cells are involved in movement, people with the condition experience characteristic tremors and stiff muscles. Current treatments address symptoms of the disease but not the underlying cause.

Researchers have pursued the idea that pluripotent stem cells, which can form any cell type in the body, could replace dead dopamine-making neurons in people with Parkinsons, and thus potentially halt or even reverse disease progression. Embryonic stem cells, derived from human embryos, have this capacity, but they have been the subject of ethical debates. Induced pluripotent stem (iPS) cells, which are made by coaxing adult cells into an embryonic-like state, have the same versatility without the associated ethical concerns.

Takahashis team transformed iPS cells derived from both healthy people and those with Parkinsons into dopamine-producing neurons. They then transplanted these cells into macaque monkeys with a form of the disease induced by a neuron-killing toxin.

The transplanted brain cells survived for at least two years and formed connections with the monkeys brain cells, potentially explaining why the monkeys treated with cells began moving around their cages more frequently.

Crucially, Takahashis team found no sign that the transplanted cells had developed into tumours a key concern with treatments that involve pluripotent cells or that they evoked an immune response that couldnt be controlled with immune-suppressing drugs.

Its addressing a set of critical issues that need to be investigated before one can, with confidence, move to using the cells in humans, says Anders Bjorklund, a neuroscientist at Lund University in Sweden.

I hope we can begin a clinical trial by the end of next year, says Takahashi. Such a trial would be the first iPS cell trial for Parkinson's. In 2014, a Japanese woman in her 70s became the first person to receive cells derived from iPS cells, to treat her macular degeneration.

In theory, iPS cells could be tailor-made for individual patients, which would eliminate the need to use drugs that suppress a possible immune response to foreign tissues.

But customized iPS cells are expensive to make and can take a couple months to derive and grow, Takahashi notes. So his team instead plans to establish iPS cell lines from healthy people and then use immune cell biomarkers to match them to people with Parkinsons in the hope of minimizing the immune response (and therefore the need for drugs to blunt the attack).

In a study described in an accompanying paper in Nature Communications2, Takahashis team implanted into monkeys iPS-cell-derived neurons from different macaques. They found that transplants between monkeys carrying similar white blood cell markers triggered a muted immune reaction.

Earlier this year, Chinese researchers began a Parkinsons trial that used a different approach: giving patients neural-precursor cells made from embryonic stem cells, which are intended to develop into mature dopamine-producing neurons. A year earlier, in a separate trial, patients in Australia received similar cells. But some researchers have expressed concerns that the immature transplanted cells could develop tumour-causing mutations.

Meanwhile, researchers who are part of a Parkinsons stem-cell therapy consortium called GForce-PD, of which Takahashis team is a member, are set to bring still other approaches to the clinic. Teams in the United States, Sweden and the United Kingdom are all planning trials to transplant dopamine-producing neurons made from embryonic stem cells into humans. Previously established lines of embryonic stem cells have the benefit that they are well studied and can be grown in large quantities, and so all trial participants can receive a standardized treatment, notes Bjorklund, also a consortium member.

Jeanne Loring, a stem-cell scientist at the Scripps Research Institute in La Jolla, California, favours transplanting iPS-derived neurons made from a patients own cells. Although expensive, this approach avoids dangerous immunosuppressive drugs, she says. And because iPS cells are established anew for each patient, the lines go through relatively few cell divisions, minimizing the risk that they will develop tumour-causing mutations. Loring hopes to begin her teams trial in 2019. This shouldnt be a race and were cheering for success by all, she says.

Lorenz Studer, a stem-cell scientist at the Memorial Sloan Kettering Cancer Center in New York City who is working on a trial that will use neurons made from embryonic stem cells, says that there are still issues to work out, such as the number of cells needed in each transplant procedure. But he says that the latest study is a sign that we are ready to move forward.

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Reprogrammed cells relieve Parkinson's symptoms in trials - Nature.com