Archive for February, 2015
'Gene Therapy Cardiovascular Insight: Pipeline Assessment, Market Trend, Technology and Competitive Landscape'
Albany, NewYork (PRWEB) February 25, 2015
Researchmoz.us announces the latest addition to its growing database of analytical market research reports. The new report, titled Gene Therapy Cardiovascular Insight: Pipeline Assessment, Market Trend, Technology and Competitive Landscape, looks into the value chain of gene therapy and its association with cardiovascular treatments.
The report goes over the fundamentals of gene therapy in brief, explaining its biological mechanism and providing some historic background to better understand the growing influence of gene therapy in the healthcare sector and more particularly in the application of cardiovascular gene therapy. It also covers some of the jargon of the gene therapy sector for better comprehension of the detailed discussion of pipeline products.
Read Full Report With TOC at http://www.researchmoz.us/gene-therapy-cardiovascular-insight-pipeline-assessment-market-trend-technology-and-competitive-landscape-report.html
The report goes on to describe the determinant conditions in the cardiovascular gene therapy market, including the competitive landscape of the market and a detailed examination of the potential impact of market drivers and restraining factors. It describes the major products currently dominating the cardiovascular gene therapy market as well as the most potentially influential products and therapies in the pipeline. The analysis of the major pipeline products includes an evaluation of the competitive landscape concerning the products in questionthe market players developing them and the impact they could have on the markets competitive hierarchy.
The report elaborates upon the product description and technological background of the cardiovascular gene therapy in question, as well as the corporate aspect of it such as development partners and licensors and collaborators, and the stage of development which the product currently occupies.
The publication also includes a detailed overview of the pre-clinical and clinical outcomes of gene therapies and various biochemical aspects of the therapy such as the vector used in the procedure, the gene targeted by the therapy and localization, and an in-depth explanation of the mechanism by which the therapy operates. The report also covers dormant and discontinued products, which helps gain an understanding of what the market isnt ready for, or wasnt ready for at the time of the discontinuation. The pipeline cardiovascular gene therapies covered in the report include Gendicine, Rexin G, and Glybera.
Through the detailed analysis of all aspects related to the cardiovascular gene therapy market, the report provides in-depth insights on which to base winning market strategies.
In all, the report covers more than 25 cardiovascular gene therapy products from more than 20 manufacturers. The companies use 8 distinct technological support systems that have their own set of strengths and weaknesses, which are profiled in the report. As far as vectors are concerned, 50% of the total vectors studies are non-viral vectors, 46% are viral vectors, while a minuscule 4% are RNAi therapeutics.
All Latest Market Research Report at http://www.researchmoz.us/latest-report.html
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'Gene Therapy Cardiovascular Insight: Pipeline Assessment, Market Trend, Technology and Competitive Landscape'
Woman swears by Multiple Sclerosis remedy
IT IS expensive and controversial and the medical community is still divided about its success, but Jenni Saunders is living proof Russia's controversial stem cell treatment program can work.
The Kawana Island resident spent 30 days in Moscow in December receiving stem cell treatment she hoped would help provide some relief from the multiple sclerosis that has been slowly crippling her body for 30 years.
It has been 10 weeks since Ms Saunders' return and she is ecstatic with the results.
The 60-year-old can literally jump for joy.
It's been "years" since Ms Saunders was able to lift both feet off the ground, so the small leap in the air is a giant leap for her.
"I have seen several improvements in the last nine to 10 weeks," she said.
"The pins and needles in my hands and feet are virtually gone and I can stand up with my eyes closed.
"This might not sound like a lot to many people, but to me it is significant."
She says she is the oldest Australian to have attempted the $60,000 treatment, excluding the cost of flights.
The stem cell treatment is not approved for MS sufferers in Australia and people like Ms Saunders have to raise money to pay for the trip, even though it is available in other parts of the world.
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Woman swears by Multiple Sclerosis remedy
Stem cellrecruiting hydrogels based on self-assembling peptides for tissue regeneration
Figure 1. Stem CellRecruiting Hydrogels Based on Self-Assembling Peptides
The Materials for Biomaterials session Best Contribution Award presented by Steve Zinkle goes to Youngmee Jung, Korea Institute of Science and Technology, for the oral presentation Self-assembling peptide nanofiber coupled with neuropeptide substance P for stem cell recruitment.
As a winner of the above Materials Today Asia Contribution Award, Yongmee Jung and Soo Hyun Kim discuss their work with us.
Stem cellbased therapy in regenerative medicine may be one of the best approaches for wound healing and tissue regeneration. Many studies have shown that the trophic effects of transplanted stem cells enhance the treatment of lung, liver, and skin injuries, as well as myocardial infarction [1]. However, although stem cell transplantationincluding cell isolation and cell culture in vitroresults in a good prognosis, there are some limitations, such as high cost, invasiveness, the shortage of cell sources, and the risk of tumorigenesis [2]. To overcome these limitations, technologies for recruiting endogenous stem cells to the site of injury may provide another promising approach, mimicking in situ tissue regeneration by the bodys own wound healing process. Unlike cell-based therapies, this strategy does not need outside cell sources or in vitro cell manipulation. Host stem cells can be mobilized using granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), or stromal cellderived factor-1 alpha (SDF-1), each of which upregulates adhesion molecules and activates chemokine signaling [3]. It has been reported that substance P (SP), another candidate for recruitment of host stem cells, is an injury-inducible factor that acts early in the wound healing process to mobilize CD29+ stromal-like cells, and thus could be used for tissue regeneration [1].
To achieve effective delivery of SP for an extended period and improve the engraftment of recruited cells at the injured site, scaffolds can be constructed from hydrogels with microenvironments similar to the native tissue. Of particular interest are self-assembling peptide (SAP)based hydrogels, which are typically composed of alternating hydrophilic and hydrophobic amino acids organized into 510 nm fibers and assembled into three-dimensional nanofibrous structures under in vivo conditions [4]. The resulting structure resembles nanostructured environments such as collagen hierarchical structures that promote adhesion, proliferation, and differentiation of cells. Furthermore, SAP is versatile enough to incorporate specific motifs based on the desired function with chemical coupling by peptide bond [5].
Recently, we designed bioactive peptide hydrogels that are able to recruit mesenchymal stem cells by coupling SAP to SP. The mixture of SAP and SP-coupled SAP can successfully maintain its nanofibrous structure and be assembled into a 3D scaffold at physiological conditions.
We confirmed the ability of this SP-coupled SAP to attract stem cells both by in vitro cell migration assay and by in vivo real-time cell tracking assay. In vitro, many cells migrated through the 8-m membrane pores and settled onto the lower surfaces of Transwell plates under the influence of SP-coupled SAP. In vivo, we injected the hydrogels into the subcutaneous tissue in nude mice and injected labeled human mesenchymal stem cells (hMSCs) into the tail vein. The migration of the injected cells was tracked in real time using a multispectral imaging system, which demonstrated that the labeled hMSCs supplied via intravenous injection were recruited to the hydrogel-injected site (Figure) [6]. We then applied our bioactive peptide hydrogels, SAP coupled with SP, to several disease models to evaluate their stem cell recruitment abilities and treatment effects on injured tissues. We have studied the effects of these hydrogels on animal models of ischemic hind limb, calvarial defect, myocardial infarction, osteoarthritis, and skin wounds. We observed in each case that in the group treated with SP-coupled peptide hydrogels, many MSCs were recruited to the injured sites, and cell apoptosis and fibrosis of injured tissues were both conspicuously decreased. Moreover, the regeneration of site-specific tissues was enhanced with the injection of stem cellrecruiting peptide hydrogels in various defect models, and tissue functions were accordingly improved without cell transplantation [2, 5, 6]. In conclusion, we have developed injectable bioactive peptides that can recruit MSCs and have evaluated their therapeutic potential on animal defect models. By applying these peptide hydrogels, we were able to deliver SP over an extended period and provide 3D microenvironments to injured regions, allowing bioactive peptides to recruit MSCs successfully, prevent cell apoptosis, and promote tissue regeneration leading to a full recovery of defects. We expect that stem cellrecruiting hydrogels based on SAP could be one of the most powerful tools for tissue regeneration without cell transplantation through the recruitment of endogenous stem cells.
This work was supported by the KIST Institutional Program
1. H. S. Hong, et al., Nat. Med., 15 (2009), pp. 425435 2. J. H. Kim, et al., Biomaterials, 34 (2013), pp. 16571668 3. T. Lapidot, I. Petit, Exp. Hematol., 30 (2002), pp. 973981 4. S. Zhang, et al., Semin. Cancer Biol., 15 (5) (2005), pp. 413420 5. J. E. Kim, et al., Int. J. Nanomedicine, 9 (Suppl 1) (2014), pp. 141157 6. S. H. Kim, et al., Tissue Eng. Part A, E-Pub (2014)
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Stem cellrecruiting hydrogels based on self-assembling peptides for tissue regeneration
Global Stem Cells Group, Inc. Announces Launch of New Stem Cell Harvesting Products
MIAMI (PRWEB) February 24, 2015
In answer to industry-wide requests for more accessible solutions to stem cell procedures, Global Stem Cells Group, Inc. and Regenestem have announced the launch of two new stem cell harvesting and isolation kits.
The Regenestem BMAC 60 mL concentrating system is a high performing concentrating system for bone marrow aspirate. This kit come complete with a bone marrow filter, a bone marrow aspirating needle and a locking syringe to help maintain suction during the aspirating process. The BMAC 60 kit includes bone marrow concentrate up to 11 times the baseline values, to produce 6-8 mL BMC from a 60 mL sample of bone marrow aspirate.
The Regenestem 60 mL Adipose Derived Stem Cell (ADSC) Kit System includes all the tools and consumables for the extraction of adipose-derived stem cells from 60 mL of lipoaspirated fat. The ADSC kit is currently being used in clinical procedures for lung disease, intra-articular injections for osteoarthritis of the knee and hip, cosmetic surgery and acne scarring, dermal injections, stem cell enriched fat transfer, wounds, chronic ulcers and other chronic conditions. The enzymatic component used to obtain the stromal vascular fraction (SVF) is provided by Adistem.
The Regenestem ADSC Kit System is available in three versions:
Gold, to conduct in-office stem cell procedures with certified GMP components for reliable performance.
Platinum, with all the benefits of the basic (gold) kit plus a sterilized PRP close system with vortex engineering method to minimize platelet loss. One set of individually packed Tulip Gems instruments are added for safe and precise adipose tissue extraction.
Titanium, the perfect state-of-the-art deluxe kit system used by a growing number of regenerative medicine physicians and recognized as the perfect preparation for virtually all clinical applications. Built with Emcyte technology, the Regenestem Titanium kit has been independently reviewed and proven in various critical performance points that make a difference in patient outcomes.
The Titanium kit is currently being used in topical procedures such as intra-articular injection for osteoarthritis of the knee and hip, cosmetic surgery and acne scarring, dermal injection, stem cell enriched fat transfer, wounds chronic ulcers among other chronic conditions.
According to Global Stem Cells Group CEO Benito Novas, the entire Global Stem Cells Group faculty and scientific advisory board worked together to develop the kits.
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Global Stem Cells Group, Inc. Announces Launch of New Stem Cell Harvesting Products
Stem cell breakthrough may allow same gender couples to create babies
Researchers from Cambridge University and Israels Weizmann Institute of Science are claiming a stem cell research breakthrough that would allow a baby to be created from the skin cells from two adults, no matter their gender. This potentially allows for infertile couples to have their own children without resorting to sperm or egg donors, and may provide the means for same sex couples to produce their own babies.
Previously only successful in experiments on mice, the new research has been conducted on human cells for the first time. In this study, the researchers paired stem cell lines from embryos with the skin of a range of different adults, with the resultant cells compared to aborted fetuses to determine an identical match.
Techniques devised to create same-sex offspring are not new. Some experiments involve the manipulation of fibroblasts in mice resulting in offspring with the genetic traits of multiple male mice, whilst others have used bone marrow stem cells extracted from males to trigger spermatogonia.
However, in this latest research, stem cells and adult human skin have been combined for the first time to create an entire new germ-cell line (that is, cells that will become embryos). Derived from ten different donor sources, the new germ-cell lines were created from 10 different donor sources five embryos and five adults.
Intrinsic to this pairing was the SOX17 gene. A master gene, SOX17 usually works to direct stem cells to be programmed to become whatever organs or body parts are required in other research this techniques has been used to create lung, gut, and pancreas cells.
The manipulation of the gene to be part of a primordial germ cell specification (that is, direct it to create cells that will become an entire human), however, is a new development pioneered by the team and has allowed them to follow this discovery with actually making primordial germ cells in the lab. This stage in a babys development is known as "specification", and once primordial germ cells become specified, they continue to develop inexorably toward precursor sperm or ova cells.
Creating human egg and sperm cells from the skin of two adults of the same gender immediately raises the possibility of same sex couples procreating and offering an alternate pregnancy path for infertile couples. Of course, it also opens the door to a new minefield of ethical and moral implications, but the researchers note that many people may potentially benefit from the technique.
The results of the research were published in the online journal Cell.
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Stem cell breakthrough may allow same gender couples to create babies
Scientists claim they can create babies for gay couples
A scientific breakthrough gets gay groups all excited about the possibility of creating egg and sperm cells from parents of the same sex.
CAMBRIDGE: Scientists at the University of Cambridge in collaboration with the Weitzmann Institute in Israel successfully used skin from five adults to artificially create germ cells or stem cells, responsible for making sperm and eggs in the body.
According to The Daily Mail UK, Jacob Hanna, the specialist leading the projects Israeli arm claimed that the technique could be developed to create a baby, in just two years time.
They also reported Cambridge Universitys Professor Azim Surani as saying:We have succeeded in the first and most important step of this process, which is to show we can make these very early human stem cells in a dish.
The Daily Nation, however, explained that what the Cambridge researchers did was identify the gene which determined which cells would become sperm and egg, and harvested them by culturing them with human embryonic stem cells, for five days.
When an egg is fertilised by a sperm, they develop into foetus or the placenta. Some become stem cells, while others become germ cells and subsequently sperm and eggs. But this isnt the same as artificial sperm and eggs.
For now, Surani said the process would contribute to scientists understanding human genetics and diseases related to aging, as they discovered that one of the occurrences in germ cells included epigenetic mutations, where cell mistakes that occur with age, were wiped out so the cell is regenerated and reset.
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Scientists claim they can create babies for gay couples
Europe Approves Holoclar, the First Stem Cell-Based Medicinal Product
Parma And Modena, Italy (ots/PRNewswire) -
The collaboration between a public excellent research center and a solid private pharmaceutical company allowed to achieve an extraordinary result, entirely "made in Italy": the first medicinal product containing stem cells approved in the Western world
The European Commission has granted a conditional marketing authorization, under Regulation (EC) No 726/2004, to Holoclar(R), an advanced therapy based on autologous stem cells and capable to restore the eyesight of patients with severe cornea damage. Holoclar(R) is manufactured by Holostem Terapie Avanzate (Holostem Advanced Therapies) - a spin-off of the University of Modena and Reggio Emilia - at the Centre for Regenerative Medicine "Stefano Ferrari" (CMR) of the same University.
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"Holoclar is the very first medicinal product based on stem cells to be approved and formally registered in the Western world," states Andrea Chiesi, Director of R&D Portfolio Management of Chiesi Farmaceutici S.p.A. and CEO of Holostem Terapie Avanzate. "This record," continues Andrea Chiesi, "shows that the partnership between the public and private sectors is not only possible, but is probably the best strategy for the development of stem cell-based regenerative medicine, particularly when autologous cells are used. Holostem is now considered as a business model to translate into clinics the results obtained by scientific research in this field."
Underlying Holoclar(R) are more than 20 years of excellence in research, conducted by a team of internationally renowned scientists in the field of epithelial stem cell biology aimed at clinical translation. European Directive 1394/2007 substantially equalizes advanced cell therapies to medicines and imposes, among other things, that cell cultures has to be manufactured only in GMP-certified facilities (GMP: Good Manufacturing Practice). Thanks to the investments of Chiesi Farmaceutici, the Centre for Regenerative Medicine in Modena - where Holostem operates - was certified as GMP compliant and continue to follow the path towards the registration of this newly developed advanced therapy.
"The authorization process has been long and complex, but the result achieved today shows that cells can be cultured according to pharmaceutical standards appropriate to guarantee safety and efficacy," adds Professor Michele De Luca, Scientific Director and co-founder of Holostem, as well as Director of the CMR of the University of Modena. "In addition, in a period of great confusion about the real therapeutic possibilities of stem cells, such as the one we are living in, being able to demonstrate that stem cells can be definitely safe and successful in a controlled clinical setting is more important than ever."
To explain how Holoclar(R) works is Professor Graziella Pellegrini, Coordinator of cell therapy at CMR, as well as director of R&D and co-founder of Holostem, who authored, together with Professor De Luca, the research and designed the product development: "After developing cell cultures based on epithelial stem cells for the treatment of various disorders of the stratified epithelia - from the skin for full-thickness burns to the reconstruction of the urethra - we discovered that the stem cells that allow the regeneration of the cornea reside in a small area at the border between the cornea (the transparent part at the center of the eye) and the conjunctiva (the contiguous white part), which is called 'the limbus'. When thermal or chemical burns of the ocular surface damage irreversibly this stem cell reserve, the corneal surface - which in a healthy eye completely renews itself approximately every six/nine months - stops regenerating and the conjunctiva gradually begins to cover the cornea with a white coating, that prevents vision and causes chronic pain and inflammation. If in at least one of the eyes of the patient even a small residue of undamaged limbus is left, we areable to reconstruct in a laboratory the epithelium that covers the corneal surface, thanks to the stem cells harvested through a 1-2mmsquared biopsy. This graft of epithelium - Holoclar(R), precisely - that looks like a kind of contact lens, is then transplanted into the patient and allows to obtain a long-term transparent cornea and a full recovery of visual acuity, without causing any rejection reaction, because it consists of cells of the patient him/herself."
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Europe Approves Holoclar, the First Stem Cell-Based Medicinal Product
Generation of Endoderm derived Human iPS cells from …
Hepatology. Author manuscript; available in PMC 2011 May 1.
Published in final edited form as:
PMCID: PMC2925460
NIHMSID: NIHMS221023
Recent advances in induced pluripotent stem (iPS) cell research significantly changed our perspective on regenerative medicine. Patient specific iPS cells have been derived not only for disease modeling but also as sources for cell replacement therapy. However, there have been insufficient data to prove that iPS cells are functionally equivalent to hES cells or safer than hES cells. There are several important issues which need to be addressed and foremost are the safety and efficacy of human iPS cells from different origins. Human iPS cells have been derived mostly from cells originated from mesoderm, with a few cases from ectoderm. So far there has been no report of endoderm derived human iPS cells, preventing comprehensive comparative investigations on the quality of human iPS cells from different origins.
Here we show for the first time reprogramming of human endoderm derived cells (i.e. primary hepatocytes) to pluripotency. Hepatocyte-derived iPS cells appear indistinguishable from human embryonic stem cells in colony morphology, growth properties, expression of pluripotency-associated transcription factors and surface markers, and differentiation potential in embryoid body formation and teratoma assays. In addition, these cells were able to directly differentiate into definitive endoderm, hepatic progenitors, and mature hepatocytes. The technology to develop endoderm derived human iPS cell lines, together with other established cell lines, will provide a foundation to elucidate the mechanisms of cellular reprogramming and to study the safety and efficacy of differentially originated human iPS cells for cell therapy. For studying liver disease pathogenesis, this technology also provides a potentially more amenable system to generate liver disease specific iPS cells.
Recent advances in induced pluripotent stem (iPS) cell research have provided great potential for these somatic cell-derived stem cells as sources for cell replacement therapy and for establishing disease models.114 Human iPS cells have been shown to be pluripotent in in vitro differentiation and in vivo teratoma assays, similar to human embryonic stem (hES) cells.914 Disease-specific iPS cell lines have been generated from fibroblasts and blood cells and some of the disease features have been recapitulated in tissue culture after directed differentiation of the iPS cells, demonstrating the power of this technology in disease modeling.13,15 However, several key issues have to be addressed in order for the iPS cells to be used for clinical purposes. First, although pluripotency has been demonstrated, it is premature to claim that iPS cells are functionally equivalent to hES cells. In fact, one study has suggested that iPS cells have distinct protein-coding and microRNA gene expression signatures from ES cells.1 These differences can not be completely explained by the reactivation of transgenes used in the reprogramming process since human iPS cells generated without viral or transgene integration also displayed a different transcriptional signature compared to hES cells.2 Secondly it was demonstrated that human iPS cells retained certain gene expression of the parent cells, suggesting that iPS cells from different origins may possess different capacity to differentiate.2 This issue is important not only for the purposes of generating functional cell types for therapy but also for safety implications. A comprehensive study using various mouse iPS cells has demonstrated that the origin of the iPS cells had a profound influence on the tumor-forming propensities in a cell transplantation therapy model.3 Mouse tail-tip fibroblast-iPS cells (mesoderm origin) showed the highest tumorigenic propensity, whereas gastric epithelial cell- and hepatocyte-iPS cells (both are endoderm) showed lower propensities.3 It is therefore extremely important to establish human iPS cell lines from multiple origins and thoroughly examine the source impact on both the safety issues and their differentiation potentials. In addition, the ability to reprogram human hepatocytes is crucial for developing liver disease models using iPS cells, especially for certain liver diseases carrying acquired somatic mutations which occur only in hepatocytes of patients, but not in other cell types.1620
In the mouse, iPS cells have been generated from derivatives of all three embryonic germ layers, including mesodermal fibroblasts,6 epithelial cells of endodermal origin7 and ectodermal keratinocytes,8 whereas human iPS cells have been produced mostly from mesoderm (fibroblasts and blood cells) or from ectoderm (keratinocytes and neural stem cells).913,21,22 Here we show reprogramming of human primary hepatocytes (endoderm) to pluripotency. Hepatocyte-derived iPS cells appear indistinguishable from human embryonic stem cells in colony morphology, growth properties, expression of pluripotency-associated transcription factors and surface markers, and differentiation potential in embryoid body (EB) formation as well as teratoma assays. In addition these cells were able to directly differentiate into definitive endoderm, hepatic progenitors, and mature hepatocytes.
Our study lays the ground work necessary to elucidate the mechanisms of cellular reprogramming and to study the safety and efficacy of differentially originated human iPS cells in cell therapy.
Primary human hepatocytes were obtained from Lonza plated on collagen 1 and matrigel coated dishes, and cultured in serum containing WEM (Willians' Medium E), Gentamicin, Dexamethasone 10 mM, FBS 5%, L-Glutamine, Hepes 15mM, Insulin 4 mg/ml with 50ng/ml of HGF and EGF. Medium for culturing hES cells and iPS cells is Knockout DMEM supplemented with 20% KOSR, NEAA, 2-ME, GlutaMAX, 6 ng/ml basic fibroblast growth factor (all Invitrogen). hESC lines WA09 (H9) and WA01 (H1) (WiCell) were cultured on irradiated MEF feeder layers in ES medium. This study was done in accordance with Johns Hopkins ESCRO regulations and following a protocol approved by the Johns Hopkins IRB.
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Generation of Endoderm derived Human iPS cells from ...
T-Cell Therapy Clinical Trial Now Offered to Cancer Patients at C.S. Mott Children's Hospital
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Newswise ANN ARBOR, Mich. A clinical trial using T-cell therapy that uses the patients own immune cells to hunt down cancer cells is now being offered at the University of Michigans C.S. Mott Childrens Hospital.
For patients for whom weve exhausted all other options, this therapy has provided hope against a highly aggressive form of ALL, in situations where nothing else has been successful, says John Levine, M.D., clinical director of the Pediatric Blood and Marrow Transplantation Program at C.S. Mott Childrens Hospital.
To begin the treatment process, researchers first extract a patients own T cells. They then use bioengineering techniques to reprogram each patients T cells into chimeric antigen receptor cells the CTL019 cells custom-designed to bind to a protein called CD19 that exists only on the surface of B cells. After being returned to the patients body, the CTL019 cells proliferate and then hunt B cells that express CD19. They also may persist in the circulation, which may guard against the cancers recurrence.
We are very proud to play an active role in this exciting new research that can offer new breakthroughs and hope for our pediatric cancer patients, says Levine, a professor of pediatrics in the University of Michigan Medical School.
In July 2014, the U.S. Food and Drug Administration designated CTL019 as a Breakthrough Therapy, helping to expedite its progress into broader clinical trials.
The trial opened in late October at Mott. Patients interested in participating should contact the center at 1-800-865-1125 to determine their eligibility.
Side effects from the treatment can include symptoms of cytokine release syndrome (CRS), which occurs when CAR cells and multiply in the patients body resulting in the release of cytokines. CRS symptoms include varying degrees of flu-like symptoms with high fevers, nausea, muscle pain, and in some cases, low blood pressure and breathing difficulties. To find out more, go to:
https://umclinicalstudies.org/HUM00086954?topics=14304 https://clinicaltrials.gov/ct2/show/study/NCT02228096?term=ctl019&rank=1#contacts
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T-Cell Therapy Clinical Trial Now Offered to Cancer Patients at C.S. Mott Children's Hospital
Master Gene Regulatory Pathway Revealed as Key Target for Therapy of Aggressive Pediatric Brain Cancer
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Newswise Working with cells taken from children with a very rare but ferocious form of brain cancer, Johns Hopkins Kimmel Cancer Center scientists have identified a genetic pathway that acts as a master regulator of thousands of other genes and may spur cancer cell growth and resistance to anticancer treatment.
Their experiments with cells from patients with atypical teratoid/rhabdoid tumor (AT/RT) also found that selumetinib, an experimental anticancer drug currently in clinical trials for other childhood brain cancers, can disrupt part of the molecular pathway regulated by one of these factors, according to a research team led by Eric Raabe, M.D., Ph.D., an assistant professor of oncology at the Johns Hopkins University School of Medicine.
AT/RT mostly strikes children 6 and younger, and the survival rate is less than 50 percent even with aggressive surgery, radiation and chemotherapy, treatments that can also disrupt thinking, learning and growth. AT/RT accounts for 1 percent of more than 4,500 reported pediatric brain tumors in the U.S., but it is more common in very young children, and it represents 10 percent of all brain tumors in infants.
Whats exciting about this study is that it identifies new ways we can treat AT/RT with experimental drugs already being tested in pediatric patients, Raabe says. Because few outright genetic mutations and potential drug targets have been linked to AT/RT, Raabe and his colleagues turned their attention to genes that could regulate thousands of other genes in AT/RT cancer cells. Experiments in fruit flies had already suggested a gene known as LIN28 could be important in regulating other genes involved in the development of brain tumors. Specifically, the LIN28 protein helps regulate thousands of RNA molecules in normal stem cells, giving them the ability to grow, proliferate and resist damage.
These factors provide stem cells with characteristics that cancer cells also have, such as resistance to environmental insults. These help tumor cells survive chemotherapy and radiation, says Raabe. These proteins also help stem cells move around the body, an advantage cancer cells need to metastasize.
In a report on one of their studies, published Dec. 26 in the journal Oncotarget, the researchers examined cell lines derived from pediatric AT/RT patients and the tumors themselves. They found that the two members of the LIN28 family of genes were highly expressed in 78 percent of the samples, and that blocking LIN28 expression with specially targeted gene silencers called short hairpin RNAs curbed the tumor cells growth and proliferation and triggered cell death. When Raabe and colleagues blocked LIN28A in AT/RT tumor cells transplanted into mice, they were able to more than double the mices life span, from 48 to 115 days.
Using selumetinib in cell line experiments, the scientists cut AT/RT tumor cell proliferation in half and quadrupled the rate of cell death in some cell lines. Raabe says the drug appeared to be disrupting a key molecular pathway controlled by LIN28.
In a second study, described in the Journal of Neuropathology and Experimental Neurology, Raabe and his colleagues examined another factor in the LIN28 pathway, called HMGA2, which is also highly expressed in AT/RT tumors. They again used short pieces of RNA to silence HMGA2, which led to lower levels of cell growth and proliferation and increased cell death. Blocking HMGA2 also doubled the survival rate of mice implanted with tumors derived from pediatric AT/RT cell lines from 58 to 153 days.
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Master Gene Regulatory Pathway Revealed as Key Target for Therapy of Aggressive Pediatric Brain Cancer
Study Nearly Triples the Locations in the Human Genome That Harbor MicroRNAs
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Newswise (PHILADELPHIA) According to the public databases, there are currently approximately 1,900 locations in the human genome that produce microRNAs (miRNAs), the small and powerful non-coding molecules that regulate numerous cellular processes by reducing the abundance of their targets. New research published in the Proceedings of the National Academy of Sciences (PNAS) this week adds another roughly 3,400 such locations to that list. Many of the miRNA molecules that are produced from these newly discovered locations are tissue-specific and also human-specific. The finding has big implications for research into how miRNAs drive disease.
By analyzing human deep-sequencing data, we discovered many new locations in the human genome that produce miRNAs. Our findings effectively triple the number of miRNA-generating loci that are now known says Isidore Rigoutsos, Ph.D., Director of the Computational Medicine Center at Thomas Jefferson University, who led the study. This new collection will help researchers gain insights into the multiple roles that miRNAs play in various tissues and diseases.
For nearly three years, the team collected and sequenced RNA from dozens of healthy and diseased individuals. The samples came from pancreas, breast, platelets, blood, prostate, and brain. To their collection they also added publicly available data eventually reaching more than 1,300 analyzed samples representing 13 human tissue types. Their analyses uncovered 3,356 new locations in the human genome that generate over 3,700 previously undescribed miRNAs.
For a handful of the 13 tissues they studied, the team also had access to information describing miRNA association with Argonaute, an essential protein member of the regulatory complex that enables miRNA to interact with their targets. They found that 45 percent of the newly discovered miRNAs were in fact associated with Argonaute, a further indication that these molecules are involved in gene regulation. We anticipate that many more of the newly discovered miRNAs will be found loaded on Argonaute as additional such data become available for the other tissues, says Eric Londin, Ph.D., an Assistant Professor and co-first author together with Phillipe Loher, M.S., a computational biologist and software engineer, both members of Jeffersons Computational Medicine Center.
One of the key design choices that the team made was to not limit their search to conserved genomic sequences, i.e. to only those sequences that are shared across multiple organisms. Instead the researchers scanned the genome much more broadly. Advances in sequencing technology of the last several years made it easier to generate more data, from more tissues, and do so faster, says Dr. Rigoutsos who is also a researcher at the Sidney Kimmel Cancer Center at Jefferson. Investigating the alluring possibility that miRNAs with important roles might exist only in humans was within reach. And this is what we set out to do.
Of the new molecules, 56.7 are specific to humans and most of them (94.4 percent) are found only in primates. Because of this organism-specificity these RNA molecules are involved in regulatory events that are absent from model organisms such as mouse and the fruit fly.
Tissue-specificity is another important characteristic of these new miRNAs. It means that these molecules are behind molecular events that are present in a single tissue, or in only a few tissues. Some of these molecules could potentially prove useful as novel tissue-specific disease biomarkers.
The tissue- and primate-specificity of the new molecules are expected to have important implications for the communitys attempts to understand the causes of diseases. A first step in that direction requires the identification and validation of the targets for each of these 3,707 new miRNAs. To assist in these efforts, the team generated computational predictions of each miRNAs putative targets that are available from the Computational Medicine Centers website.
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Study Nearly Triples the Locations in the Human Genome That Harbor MicroRNAs
Genetic medicine under the spotlight
LEADING experts are hosting a special event to highlight pioneering genetic work carried out at Newcastle University, including the controversial three-parent IVF technique.
Genetic Matters will focus on a series of high-profile talks, including mitochondrial donation, the future of genetic diagnostics and life after being diagnosed with a rare illness.
Newcastle Universitys 100,000 Genome Project will also be discussed. The world-leading scheme aims to map 100,000 complete genetic codes to uncover DNA data that can be used to develop personalised diagnostic procedures and drugs.
Dr Katarzyna Pirog, from the Institute of Genetic Medicine, said: Genetics Matters is an event designed specifically for members of the public, and is an exciting opportunity to meet scientists and learn about the state-of-the-art genetic research that happens at Newcastle University.
With a series of high profile talks, presentations from patient groups and charity organisations, and hands on research tables, it is a packed day giving everyone a chance to talk to real scientists and ask them any questions to do with genetic research.
Prof Sir John Burn, head of Newcastle Universitys Institute of Human Genetics, will close the event with a talk about the future of rare disease research.
He said: There are more than 8,000 rare diseases, mostly due to faults in one or more genes and the number grows as sequencing gets cheaper and faster. One in 17 people has a rare genetic disorder and providing their care is a major health cost.
As we learn how these rare diseases are caused we gain new insights into the causes of common diseases and can use this to develop new treatments.
Genetic Matters will take place on Friday, February 27, from 10:45am until 5pm, at the Great North Museum: Hancock in Newcastle.
To book a place at the event visit: forms.ncl.ac.uk/view.php?id=7501
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Genetic medicine under the spotlight
Genetic pathways linked to CF disease severity pinned down
Mutation of one gene is all it takes to get cystic fibrosis (CF), but disease severity depends on many other genes and proteins. For the first time, researchers at the UNC School of Medicine have identified genetic pathways -- or clusters of genes -- that play major roles in why one person with CF might never experience the worse kinds of symptoms while another person will battle severe airway infection for a lifetime.
The finding, published in the American Journal of Human Genetics, opens avenues of research toward new personalized or precision treatments to lessen pulmonary symptoms and increase life expectancy for people with cystic fibrosis.
"Right now, there are drugs being developed to fix the function of the CFTR protein that is disrupted in cystic fibrosis, but even then, some patients will respond very well to therapy and some won't," said Michael Knowles, MD, professor of pulmonary and critical care medicine and senior author of the paper. "Why is that? We think it's the genetic background -- the pathways that we identified contain genes that likely interact with the main CFTR gene mutation."
Knowles's team found that when these pathways or groups of genes are highly expressed, CF patients have less severe symptoms. When these pathways are expressed in lower amounts, patients experience a more severe form of the disease and are more likely to be hospitalized.
Wanda O'Neal, PhD, associate professor of medicine and first author, said, "Now that we've found these pathways, we need to dig into the biology to see how specific genes within them influence disease severity. This could help us not only to predict which patients will respond to a given therapy but it may also provide drug targets to lessen the severity of disease for all patients."
The CFTR gene was discovered in 1989, and since then researchers have found about 1,800 different mutations in the CFTR gene that cause cystic fibrosis. There is a new drug that works very well to correct a mutation found in about 4 percent of CF patients. There is still no FDA approved drug to correct the mutation found in about 70 percent of patients (called the DF508 mutation), though a drug company has recently shown that a combination therapy of two new drugs modestly improved lung function in some CF patients. Still, this combination therapy may not work or wouldn't work well enough for some patients, and the reason could be the complex interaction between the CFTR gene and the genetic pathways uncovered by Knowles, O'Neal, and co-senior author Fred Wright, PhD, a professor of bioinformatics and director of the bioinformatics program at North Carolina State University.
In a normal epithelial cell, the CFTR gene creates the protein that transits from the cell nucleus to the cell membrane, where it then works to maintain proper lung function. As the protein transits, there are many genes that interact with it in various ways so that it can complete the journey to the membrane and work properly in the end. In CF patients with the DF508 mutation, the CFTR gene does not fold into its correct form and cannot make it to the cell surface. In order for CF patients to be out of the woods, the DF508 protein would need help from a complex network of genes and proteins to get to the membrane.
Over the past decade, Knowles has teamed with scientists from the United States and Canada to gather thousands of genetic and blood cell samples from CF patients. One of the research goals has been to identify genes and cellular proteins that often have subtle effects inside cells but that can produce dramatic differences in disease severity. Decades of research on protein functions has allowed genes to be grouped into pathways based on common biological roles.
For this current study, Knowles and O'Neal used gene expression data from the cells collected from 750 patients gathered over the past decade from 40 sites across the United States. Along with Wright and other authors, they analyzed data on more than 4,000 pathways to find pathways that identified severe CF patients as compared to mild CF patients. They found significant genetic variation in only broad types of pathways: endomembrane pathways and HLA pathways.
This finding was telling because endomembrane genes are responsible for transporting the DF508 protein from the cell nucleus to the cell membrane and for regulating the way that proteins such as CFTR are folded into the proper functioning form. The HLA genes are widely known to have roles in immune function; they're important for protection against pathogens, such as Pseudomonas -- the commonly seen bacteria that causes pneumonia in CF patients.
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Genetic pathways linked to CF disease severity pinned down
Researchers Pin Down Genetic Pathways Linked to CF Disease Severity
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Newswise CHAPEL HILL, NC Mutation of one gene is all it takes to get cystic fibrosis (CF), but disease severity depends on many other genes and proteins. For the first time, researchers at the UNC School of Medicine have identified genetic pathways or clusters of genes that play major roles in why one person with CF might never experience the worse kinds of symptoms while another person will battle severe airway infection for a lifetime.
The finding, published in the American Journal of Human Genetics, opens avenues of research toward new personalized or precision treatments to lessen pulmonary symptoms and increase life expectancy for people with cystic fibrosis.
Right now, there are drugs being developed to fix the function of the CFTR protein that is disrupted in cystic fibrosis, but even then, some patients will respond very well to therapy and some wont, said Michael Knowles, MD, professor of pulmonary and critical care medicine and senior author of the paper. Why is that? We think its the genetic background the pathways that we identified contain genes that likely interact with the main CFTR gene mutation.
Knowless team found that when these pathways or groups of genes are highly expressed, CF patients have less severe symptoms. When these pathways are expressed in lower amounts, patients experience a more severe form of the disease and are more likely to be hospitalized.
Wanda ONeal, PhD, associate professor of medicine and first author, said, Now that weve found these pathways, we need to dig into the biology to see how specific genes within them influence disease severity. This could help us not only to predict which patients will respond to a given therapy but it may also provide drug targets to lessen the severity of disease for all patients.
The CFTR gene was discovered in 1989, and since then researchers have found about 1,800 different mutations in the CFTR gene that cause cystic fibrosis. There is a new drug that works very well to correct a mutation found in about 4 percent of CF patients. There is still no FDA approved drug to correct the mutation found in about 70 percent of patients (called the DF508 mutation), though a drug company has recently shown that a combination therapy of two new drugs modestly improved lung function in some CF patients. Still, this combination therapy may not work or wouldnt work well enough for some patients, and the reason could be the complex interaction between the CFTR gene and the genetic pathways uncovered by Knowles, ONeal, and co-senior author Fred Wright, PhD, a professor of bioinformatics and director of the bioinformatics program at North Carolina State University.
In a normal epithelial cell, the CFTR gene creates the protein that transits from the cell nucleus to the cell membrane, where it then works to maintain proper lung function. As the protein transits, there are many genes that interact with it in various ways so that it can complete the journey to the membrane and work properly in the end. In CF patients with the DF508 mutation, the CFTR gene does not fold into its correct form and cannot make it to the cell surface. In order for CF patients to be out of the woods, the DF508 protein would need help from a complex network of genes and proteins to get to the membrane.
Over the past decade, Knowles has teamed with scientists from the United States and Canada to gather thousands of genetic and blood cell samples from CF patients. One of the research goals has been to identify genes and cellular proteins that often have subtle effects inside cells but that can produce dramatic differences in disease severity. Decades of research on protein functions has allowed genes to be grouped into pathways based on common biological roles.
Continued here:
Researchers Pin Down Genetic Pathways Linked to CF Disease Severity
Personalized medicines potential grows. But what signals real progress?
This post is sponsored by the MidAmerica Healthcare Venture Forum.
The table is set for jaw-dropping growth in the genomics/personalized medicine/precision medicine space. Pick your favorite news item. Is it the presidents new plan? The big investments out of JP Morgan? Or, most recently, the breakthrough decision by the FDA around 23andMe and other genetic testing kits?
Its not about whether personalized medicine has arrived. Its here. Now its about not getting lost in the hype and focusing on what matters.
Thats why weve assembled a strong cast of clinicians and innovators at the MidAmerica Healthcare Venture Forum on March 10-11 in Chicago who will keep us on track and explain how to maximize the potential of personalized medicine. MedCitys Meghana Keshavan will lead a discussion exploring not only what the next milestones are for the industry but also where the biggest opportunities are and what areas of personalized medicine need the most support.
Join us in Chicago and youll hear from the following panelists:
New funding and fresh attention bring new opportunities. The worst-case scenario for precision medicine is for investors, entrepreneurs and other healthcare leaders to squander it by getting lost amidst the hype and euphoria.
Our panel at the MidAmerica Healthcare Venture Forum will help keep everyone on track by sharing their hands-on knowledge on what it will take to deliver real success in personalized medicine. I hope you can join us March 10-11 in Chicago to participate in the discussion.
[Photo from Flickr user Craig Cloutier]
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Personalized medicines potential grows. But what signals real progress?
Addiction can also be compulsion, gambling study shows
Researchers from Yale University have found new evidence for a link between obsessive compulsive spectrum disorder and pathological gambling, perhaps due to genetic factors.
Building off of previous research that suggested a link between addictive behavior and pathological gambling, this study is part of an ongoing effort to further classify gambling addiction on an impulse-to-compulsion spectrum. The central question of the debate is: To what extent do pathological gamblers have impulse-control problems as opposed to a compulsion to gamble? This study adds evidence that there is an element of compulsive behavior for some pathological gamblers.
We were trying to understand the relation between pathological gambling and other disorders, said Yale professor of psychiatry at the School of Medicine and the papers senior author Marc Potenza. There has been some debate in the literature about how best to consider pathological gambling whether it might fall along the impulsive-compulsive spectrum or be thought of as an addiction without the drug.
The researchers performed a twin study, using the Vietnam Era Twin Registry a compiled list of male twin veterans of the Vietnam War to study both genetic explanations of pathological gambling and its connection with latent obsessive-compulsive behavior. Twin studies allow researchers to better disentangle the complex relationship between environmental and genetic factors at play in disorders, diseases and behaviors. The researchers found a correlation between latent obsessive-compulsive behavior and pathological gambling. In addition, they found behavioral correlations between twins, suggesting a genetic component to compulsive behavior and pathological gambling.
It was unusual that the researchers decided to use a twin study, as opposed to conducting genetic testing, Potenza said. The methodology allowed the researchers to ascertain a genetic component, but without the genetic testing, they were unable to identify which genes cause this effect. That second question, Potenza said, may lead to further research.
But clinical professor at the Stanford School of Medicine Alan Ringold, an expert on OCD who is unaffiliated with the study, said he does not believe pathological gambling is related to OCD, which is an extreme enough form of obsessive behavior that it is classified as a disorder in the Diagnostic and Statistical Manual, which classifies psychiatric disorders.
Gambling is an impulse control disorder. Its not OCD, Ringold said, highlighting the controversy within the medical community about whether gambling is compulsion-based or impulse control-based.
Because the researchers only used male participants, it is unknown to what extent the results generalize to the entire population.
This is an example of being persistent, said Jeffrey Scherrer, professor in the department of family and community medicine at Saint Louis University School of Medicine. This gambling study data collection was completed around 2003, and we began some preliminary analysis. We werent able to get back together on this until many years later, so the lesson is dont give up on an idea.
Between 5 and 7 percent of Americans have a problem with gambling.
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Addiction can also be compulsion, gambling study shows
The Future of Treating Heart Disease Is Now (2015) – Video
The Future of Treating Heart Disease Is Now (2015)
At the Texas Heart Institute, the future of preventing, diagnosing, and treating heart disease is now. A look at the many ways including regenerative medicine, stem cells, genetics, imaging,...
By: Texas Heart Institute
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The Future of Treating Heart Disease Is Now (2015) - Video
Stem Cell Research & Therapy | Full text | Aromatic …
Abstract Introduction
Aromatic (ar-) turmerone is a major bioactive compound of the herb Curcuma longa. It has been suggested that ar-turmerone inhibits microglia activation, a property that may be useful in treating neurodegenerative disease. Furthermore, the effects of ar-turmerone on neural stem cells (NSCs) remain to be investigated.
We exposed primary fetal rat NSCs to various concentrations of ar-turmerone. Thereafter, cell proliferation and differentiation potential were assessed. In vivo, nave rats were treated with a single intracerebroventricular (i.c.v.) injection of ar-turmerone. Proliferative activity of endogenous NSCs was assessed in vivo, by using noninvasive positron emission tomography (PET) imaging and the tracer [18F]-fluoro-L-thymidine ([18F]FLT), as well as ex vivo.
In vitro, ar-turmerone increased dose-dependently the number of cultured NSCs, because of an increase in NSC proliferation (P<0.01). Proliferation data were supported by qPCR-data for Ki-67 mRNA. In vitro as well as in vivo, ar-turmerone promoted neuronal differentiation of NSCs. In vivo, after i.c.v. injection of ar-turmerone, proliferating NSCs were mobilized from the subventricular zone (SVZ) and the hippocampus of adult rats, as demonstrated by both [18F]FLT-PET and histology (P<0.05).
Both in vitro and in vivo data suggest that ar-turmerone induces NSC proliferation. Ar-turmerone thus constitutes a promising candidate to support regeneration in neurologic disease.
Curcumin and ar-turmerone are the major bioactive compounds of the herb Curcuma longa. Although many studies have demonstrated curcumin to possess antiinflammatory and neuroprotective properties (reviewed by [1]), to date, the effects of ar-turmerone remain to be elucidated. For example, antitumor properties, exerted via the induction of apoptosis [2] and inhibition of tumor cell invasion [3], have been attributed to ar-turmerone. Park et al. [4,5] recently suggested that ar-turmerone also possesses antiinflammatory properties resulting from the blockade of key signaling pathways in microglia. Because microglia activation is a hallmark of neuroinflammation and is associated with various neurologic disorders, including neurodegenerative diseases [6,7] and stroke [8,9], ar-turmerone constitutes a promising therapeutic agent for various neurologic disorders.
The regenerative potential of endogenous neural stem cells (NSCs) plays an important role in neurodegenerative disease and stroke. Endogenous NSCs are mobilized by cerebral ischemia [10] as well as by various neurodegenerative diseases [11,12], although their intrinsic regenerative response is insufficient to enable functional recovery. The targeted (that is, pharmacologic) activation of endogenous NSCs has been shown to enhance self-repair and recovery of function in the adult brain in both stroke [13,14] and neurodegeneration [15]. Importantly, NSCs and microglia relevantly interact with each other, thereby affecting their respective functions [16,17].
Thus, with the perspective of ar-turmerone as a therapeutic option in mind, we investigated the effects of ar-turmerone on NSCs in vitro and in vivo.
NSCs were cultured from fetal rat cortex at embryonic day 14.5, as described previously [18]. Cells were expanded as monolayer cultures in serum-free DMEM/F12 medium (Life Technologies, Darmstadt, Germany) with N2 supplement (Gibco, Karlsruhe, Germany) and fibroblast growth factor (FGF2; 10ng/ml; Invitrogen, Karlsruhe, Germany) for 5days and were replated in a 24-well plate at 10,000 cells per cm2. FGF2 was included throughout the experiments.
Ar-turmerone (Fluka, Munich, Germany) was added to cultures at replating at concentrations of 0, 1.56, 3.125, 6.25, 12.5, and 25g/ml. All experiments were performed in triplicate. After 72hours, representative pictures were taken by using an inverted fluorescence phase-contrast microscope (Keyence BZ-9000E). Three images were taken per well, and cells were counted by using the software ImageJ with a threshold of 20 px (National Institutes of Health, Bethesda, MD, USA, Version 1.47k).
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Stem Cell Research & Therapy | Full text | Aromatic ...
Cambridge university researchers' breakthrough paves way for same sex couple babies
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Researchers from Cambridge University have shown for the first time that it is possible to make human egg and sperm cells using skin from two adults of the same sex.
The scientific breakthrough may lead to a baby being made in a dish from the skin cells of two adults of the same sex, bringing hope to gay people.
The project, funded by the Wellcome Trust, was achieved at Cambridge University with Israels Weizmann Institute of Science.
The scientists used stem cell lines from embryos as well as from the skin of five different adults.
Ten different donor sources have been used so far and new germ-cell lines have been created from all of them, researchers said.
A gene called SOX1 has turned out to be critical in the process of reprogramming human cells, according to a report in a national newspaper.
The details of the technique were published in the journal Cell.
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Cambridge university researchers' breakthrough paves way for same sex couple babies
Stem Cell Research & Therapy | Full text | Aromatic …
Abstract Introduction
Aromatic (ar-) turmerone is a major bioactive compound of the herb Curcuma longa. It has been suggested that ar-turmerone inhibits microglia activation, a property that may be useful in treating neurodegenerative disease. Furthermore, the effects of ar-turmerone on neural stem cells (NSCs) remain to be investigated.
We exposed primary fetal rat NSCs to various concentrations of ar-turmerone. Thereafter, cell proliferation and differentiation potential were assessed. In vivo, nave rats were treated with a single intracerebroventricular (i.c.v.) injection of ar-turmerone. Proliferative activity of endogenous NSCs was assessed in vivo, by using noninvasive positron emission tomography (PET) imaging and the tracer [18F]-fluoro-L-thymidine ([18F]FLT), as well as ex vivo.
In vitro, ar-turmerone increased dose-dependently the number of cultured NSCs, because of an increase in NSC proliferation (P<0.01). Proliferation data were supported by qPCR-data for Ki-67 mRNA. In vitro as well as in vivo, ar-turmerone promoted neuronal differentiation of NSCs. In vivo, after i.c.v. injection of ar-turmerone, proliferating NSCs were mobilized from the subventricular zone (SVZ) and the hippocampus of adult rats, as demonstrated by both [18F]FLT-PET and histology (P<0.05).
Both in vitro and in vivo data suggest that ar-turmerone induces NSC proliferation. Ar-turmerone thus constitutes a promising candidate to support regeneration in neurologic disease.
Curcumin and ar-turmerone are the major bioactive compounds of the herb Curcuma longa. Although many studies have demonstrated curcumin to possess antiinflammatory and neuroprotective properties (reviewed by [1]), to date, the effects of ar-turmerone remain to be elucidated. For example, antitumor properties, exerted via the induction of apoptosis [2] and inhibition of tumor cell invasion [3], have been attributed to ar-turmerone. Park et al. [4,5] recently suggested that ar-turmerone also possesses antiinflammatory properties resulting from the blockade of key signaling pathways in microglia. Because microglia activation is a hallmark of neuroinflammation and is associated with various neurologic disorders, including neurodegenerative diseases [6,7] and stroke [8,9], ar-turmerone constitutes a promising therapeutic agent for various neurologic disorders.
The regenerative potential of endogenous neural stem cells (NSCs) plays an important role in neurodegenerative disease and stroke. Endogenous NSCs are mobilized by cerebral ischemia [10] as well as by various neurodegenerative diseases [11,12], although their intrinsic regenerative response is insufficient to enable functional recovery. The targeted (that is, pharmacologic) activation of endogenous NSCs has been shown to enhance self-repair and recovery of function in the adult brain in both stroke [13,14] and neurodegeneration [15]. Importantly, NSCs and microglia relevantly interact with each other, thereby affecting their respective functions [16,17].
Thus, with the perspective of ar-turmerone as a therapeutic option in mind, we investigated the effects of ar-turmerone on NSCs in vitro and in vivo.
NSCs were cultured from fetal rat cortex at embryonic day 14.5, as described previously [18]. Cells were expanded as monolayer cultures in serum-free DMEM/F12 medium (Life Technologies, Darmstadt, Germany) with N2 supplement (Gibco, Karlsruhe, Germany) and fibroblast growth factor (FGF2; 10ng/ml; Invitrogen, Karlsruhe, Germany) for 5days and were replated in a 24-well plate at 10,000 cells per cm2. FGF2 was included throughout the experiments.
Ar-turmerone (Fluka, Munich, Germany) was added to cultures at replating at concentrations of 0, 1.56, 3.125, 6.25, 12.5, and 25g/ml. All experiments were performed in triplicate. After 72hours, representative pictures were taken by using an inverted fluorescence phase-contrast microscope (Keyence BZ-9000E). Three images were taken per well, and cells were counted by using the software ImageJ with a threshold of 20 px (National Institutes of Health, Bethesda, MD, USA, Version 1.47k).
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Stem Cell Research & Therapy | Full text | Aromatic ...
Why Stem Cell Therapy? – Video
Why Stem Cell Therapy?
Dr. Bryn J. Henderson (DO, JD, FACPE, CIME) is visionary physician executive leading RMG. In this amazing education video, he is explaning clearly why patients should choose Stem Cell Therapy...
By: iManifestart
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Why Stem Cell Therapy? - Video
Stem Cell Therapy for Liver Failure Cirrhosis Kidney Damage – 6 Months After Stemcell Transplant – Video
Stem Cell Therapy for Liver Failure Cirrhosis Kidney Damage - 6 Months After Stemcell Transplant
Bruce from Perth Australia give us an update 6 Months After his cord Mesenchymal stem cell treatment for Iiver cirrhosis, kidney complications in Thailand: More here: http://stemcellthailand.org/th...
By: Regeneration Center of Thailand
New gene that may help reduce risk of GM contamination identified
Toronto, Feb 21:
Researchers, including those of Indian-origin, have identified a gene that may help reduce contamination of conventional crops by genetically modified (GM) crops.
The plant gene discovered by the University of Guelph scientists might help farmers reduce the risk of GM contamination and quell arguments against the use of transgenic food crops, Sherif Sherif, lead author of a new research paper describing the findings, said.
This is believed to be the first-ever study to identify a gene involved in altering fruit trees that normally cross-pollinate needing one plant to fertilise another into self-pollinators, he said.
Sherif said researchers might one day insert this gene into GM crops to prevent their pollen from reaching other plants.
There are a lot of transgenic crops worldwide, said plant agriculture professor Jay Subramanian, Sherifs PhD supervisor and a co-author on the paper.
There is concern about pollen from them being able to fertilise something in the wild population, thus creating super weeds, Subramanian said.
The researchers found a gene making a protein that naturally allows a small handful of plants to self-pollinate and make fruit before the flower opens.
Peaches, for example, have closed flowers, unlike their showy-flowered plum and cherry cousins that need pollen from another tree to fertilise and set fruit.
Other co-authors on the paper are Guelph professors Jaideep Mathur, Department of Molecular and Cellular Biology and Gopi Paliyath, from Department of Plant Agriculture, along with Islam El-Sharkawy, a former research associate with Subramanian; and colleagues at the National University of Singapore.
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New gene that may help reduce risk of GM contamination identified
Hermitcraft Modsauce Modpack Lets Play 06 – Advance Genetics – Video
Hermitcraft Modsauce Modpack Lets Play 06 - Advance Genetics
I have been wanting to get back in to some modded Minecraft but I didn #39;t want to do it alone. So I invited some friends to come and join.In combination of so...
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Hermitcraft Modsauce Modpack Lets Play 06 - Advance Genetics - Video
The Sims 3 – Perfect Genetics Challenge Ep.65 Benjamin the Stylist? – Video
The Sims 3 - Perfect Genetics Challenge Ep.65 Benjamin the Stylist?
Come join me on my latest journey into the complex world of sims 3 genetics, as I try to get perfect foals and perfect children. Will I succeed in getting perfect genetics in both? Can I keep...
By: GamerGirlsNetwork
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The Sims 3 - Perfect Genetics Challenge Ep.65 Benjamin the Stylist? - Video