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Myths and Facts About Male Calico Cats | LoveToKnow

Cat owners and enthusiasts have heard a number of fascinating myths about male calico cats. While they are relatively rare, with an estimated one male in 3,000 calico cat births, there is no extraordinary demand for them. They do not make good breeding studs because almost all male calicos are sterile. In fact, only about one in 10,000 male calicos is fertile.

Some people have the misconception that calico kittens and cats comprise a specific cat breed. However, calico is the description of a cat's coloration. Cats of many breeds can be a calico, or true tricolor, as a result of their genetic heritage.

Unlike cats with tortoiseshell coloring, the coats of calico cats are of three distinct colors - red, black and white, or a variation of those colors.

Male calicos are a genetic anomaly. Cats, like humans, have two sex chromosomes. Chromosomes carry genes and determine an animal's traits. The required red color for a calico cat is passed only on a female (X) chromosome. How then can a male cat inherit the red colored required for a calico cat?

To put it simply, two chromosomes determine gender. Each parent contributes one chromosome to the offspring. The mother, who has only X chromosomes, always contributes an X chromosome. The father who has both X and Y chromosomes, can contribute either an X or a Y chromosome to his offspring. Thus, it is the father who determines the sexes of his kittens. The red color gene cannot be passed to a male offspring due to unusual characteristics of the gene in question. Under certain conditions, when the red genes are passed to a female offspring, she displays not the expected red or orange coat, but the tricolor coat of a true calico cat.

How then can a male be a true calico? Sometimes there is an incomplete division of the chromosome pair when the chromosomes are separating at the time of fertilization. When that happens, the incomplete chromosome ends up attached to another of the two required chromosomes, giving the offspring one of the following combinations:

In both cases, the result is a male cat who can inherit the trait for a true calico coat. Among humans, this genetic arrangement is called Klinefelter syndrome. A male calico usually cannot sire offspring because the genetics described above almost always guarantees that he will be sterile.

One might suppose that male calicos would bring a high price among breeders because of their rarity. You may even see some websites claiming a purebred male calico cat can fetch a price as high as $1,000 to $2,000. The truth is, while they are an interesting phenomenon, they are of little interest to breeders because they are sterile. It's possible a pet owner might want to pay that amount of money to own a cat that's a rarity, but chances are if you're looking to buy a male calico cat don't expect to pay much more than you would for any regular unpedigreed house cat.

Although most male calicos are sterile, it is a good idea to neuter them to deter spraying and other unwelcome male behaviors. Despite their limitations, they are still boys at heart!

As mentioned earlier, male calico cats have distinctive tricolor coats, but they are not a separate breed. In fact, as many as 16 different cat breeds can have calico coloration, and male calicos can occur among any of those breeds. Some common breeds that may have calico coloration are:

Male calico cats are the offspring with a genetic anomaly of parents representing many possible cat breeds. While female calico cats are quite common, true male calicos are rare and of particular interest for the combination of their unique coloration and sex. While it's a myth that they can command a high price among cat fanciers, if you happen to own a male calico, you can treasure him for his rare condition and other wonderful feline attributes!

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Myths and Facts About Male Calico Cats | LoveToKnow

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10 Famous Women Scientists in History

Science and technology are often considered to be the forte of men. Nevertheless, the contribution of women to the progress of these areas cannot be disregarded. There have been numerous gifted and far-famed women scientists in history who made crucial discoveries and inventions in the world of science.

Today on our Science Blog, well take a look at some of the most famous women scientists and their achievements.

Polish-born French physicist and chemist best known for her contributions to radioactivity.

British primatologist and ethologist, widely considered to be the worlds foremost expert on chimpanzees.


German-born American physicist who received Nobel Prize for suggesting the nuclear shell model of the atomic nucleus.

American marine biologist and conservationist whose work revolutionzied the global environmental movement.

British biophysicist best known for her work on the molecular structures of coal and graphite, and X-ray diffraction.

American scientist and cytogeneticist who received Nobel Prize in 1983 for the discovery of genetic transposition.

Italian neurologist who received Nobel Prize in 1986 for the discovery of Nerve growth factor (NGF).

American biochemist and pharmacologist who received the 1988 Nobel Prize in Physiology or Medicine.

American physician who was the first woman to become a medical doctor in the United States.

German biologist who received the Albert Lasker Award for Basic Medical Research in 1991.


10 Famous Women Scientists in History

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Genetic Tests Offered (all nonprofit) | The John and …

ABCA4 Retinal Degeneration Autosomal Recessive and Autosomal DominantPlease submit parental samples (no charge) in addition to the patient's sample; requisition needed for each. ABCA4 & ELOVL4 (Leu263 del5tttCTTAA) First Tier Testing$463 12-14 weeks Allele-Specific Testing Followed by Conventional Sequencing 81479 Second Allele Testing$1,611 14-16 weeks Conventional Sequencing 81479AchromatopsiaAutosomal RecessiveCNGA3(exon 8) & CNGB3(Exon 10)First Tier Testing$2338-10 weeksConventional Sequencing81479Autosomal Recessive & X-linkedCNGA3, CNGB3, CNNM4, GNAT2, KCNV2, NBAS, OPN1LW, PDE6C, PDE6H & RPGRExome Testing$220014-16 weeksConventional Sequencing & Next Generation Sequencing81479Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy (ADNIV) Autosomal Dominant CAPN5 $373 12-14 weeks Conventional Sequencing 81479Bardet-Biedl SyndromeAutosomal RecessiveBBS1 (Met390Arg) BBS10 (Leu90 ins1T)First Tier Testing$1408-10 weeksAllele-Specific Testing81479ARL6, BBS1, BBS2, BBS4, BBS5, BBS7, BBS9, BBS10, BBS12, CEP290, INPP5E, LZTFL1, MKS1, MKKS, SDCCAG8, TRIM32 & TTC8Exome Testing$220014-16 weeksAllele-Specific Testing Followed by Conventional Sequencing and Next Generation Sequencing81479Best Disease Autosomal Dominant BEST1 (Full coding region) $373 12-14 weeks Conventional Sequencing 81406Blue Cone Monochromacy X-Linked OPNL1W - Locus Control Region $429 6-8 weeks Deletion Detection (Males Only) 81479Choroideremia X-Linked CHM (Full coding region) $485 14-16 weeks Conventional Sequencing 81479Cone-Rod DystrophyAutosomal DominantCRX (full coding region), GUCA1A(Leu151Phe) & GUCY2D (Exon 13)$2618-10 weeksConventional Sequencing81404, 81479Congenital Stationary Night BlindnessAutosomal Dominant, Autosomal Recessive & X-LinkedCACNA1F, GRM6, PDE6B & TRPM1First Tier Testing$2338-10 weeksConventional Sequencing81479CABP4, CACNA1F, GNAT1, GPR179, GRK1, GRM6, LRIT3, NYX, PDE6B, RDH5, RHO, SAG, SLC24A1, TRPM1Exome Testing$220014-16 weeksConventional Sequencing & Next Generation Sequencing81479Corneal Dystrophy-Stromal Autosomal Dominant TGFBI (Exons 4 & 11-14) $205 12-14 weeks Conventional Sequencing 81479EnhancedS-Cone Syndrome Autosomal RecessivePlease submit parental samples (no charge) in addition to the patient's sample; requisition needed for each. NR2E3 (Exons 2-8) $314 14-16 weeks Conventional Sequencing 81479Jewish Retinal Degeneration Panel - Leber Congenital Amaurosis, Retinitis Pigmentosa and Usher Syndrome Autosomal Recessive DHDDS (Lys42Glu), LCA5 (Gln279Stop), MAK (Lys429 Alu Insertion), PCDH15 (Arg245Stop), USH3A (Asn48Lys) $205 4 weeks Conventional Sequencing 81400, 81479Juvenile Open Angle Glaucoma Autosomal Dominant MYOC (full coding region) $205 12-14 weeks Conventional Sequencing 81479Juvenile X-Linked Retinoschisis X-Linked RS1 (full coding region) $233 10-12 weeks Conventional Sequencing 81479Leber Congenital AmaurosisAutosomal Recessive Please submit parental samples (no charge) in addition to the patient's sample; requisition needed for each.AIPL1, CEP290, CRB1, CRX, GUCY2D, IQCB1, LCA5, LRAT, NMNAT1, RD3, RDH12, RPE65 (entire coding region), RPGRIP1, SPATA7, TULP1First Tier Testing$95714-16 weeksAllele-Specific Testing Followed by Conventional Sequencing81404, 81406, 81408, 81479Exome Testing$28006-8 monthsAllele-Specific Testing Followed by Conventional Sequencing and Next Generation Sequencing81479Leber Hereditary Optic Neuropathy Mitochondrial 3460, 11778, 14484 $140 6-8 weeks Allele-Specific Testing 81401Malattia Leventinese Autosomal Dominant EFEMP1 (Arg345Trp mutation) $140 6-8 weeks Allele-Specific Testing 81479Norrie Disease X-Linked NDP (full coding region) $121 8-10 weeks Conventional Sequencing 81404North Carolina Macular Dystrophy Autosomal Dominant PRDM13, IRX1 $243 6-8 weeks Allele-Specific Testing and Conventional Sequencing 81479Pattern Dystrophy Autosomal Dominant RDS (full coding region) $149 8-10 weeks Conventional Sequencing 81404Primary Open Angle Glaucoma Autosomal Dominant MYOC (full coding region) $205 12-14 weeks Conventional Sequencing 81479Retinitis Pigmentosa Autosomal Dominant C1QTNF5, IMPDH1, MAK, NR2E3, PRPF3, PRPF31, PRPF8, RDH12, RDS, RHO, RP1, RP9, SNRNP200, TOPORS $320 8-10 weeks Allele-Specific Testing Followed by Conventional Sequencing 81404, 81479Retinitis Pigmentosa Autosomal Recessive ABCA4, CC2D2A, CERKL, CLRN1, CNGA1, CRB1, DHDDS, EYS, FAM161A, FLVCR1, IDH3B, IMPG2, LRAT, MAK, NR2E3, NRL, PDE6A, PDE6B, PDE6G, PROM1, RBP3, RDH12, RGR, RLBP1, RPE65, SAG, TTPA, TULP1, USH2A, ZNF513 $833 12 14 weeks Allele-Specific Testing Followed by Conventional Sequencing 81408, 81479Retinitis Pigmentosa X-Linked RP2, RPGR $865 12-14 weeks Conventional Sequencing 81479Sorsby Dystrophy Autosomal Dominant TIMP3 (Exons 1 & 5) $121 8-10 weeks Conventional Sequencing 81479Stargardt like Macular Dystrophy Autosomal Dominant ELOVL4 (Leu263 del5tttCTTAA) $140 6-8 weeks Allele-Specific Testing 81479Stargardt Disease Autosomal Recessive and Autosomal DominantPlease submit parental samples (no charge) in addition to the patient's sample; requisition needed for each. ABCA4 & ELOVL4 (Leu263 del5tttCTTAA) First Tier Testing$463 12-14 weeks Allele-Specific Testing Followed by Conventional Sequencing 81408, 81479 Second Allele Testing$1,611 14-16 weeks Conventional Sequencing 81408, 81479Usher SyndromeAutosomal RecessiveCDH23, CLRN1, MYO7A, PCDH15, USH1C, USH1G & USH2AFirst Tier Testing$5758-10 weeksAllele-Specific Testing Followed by Conventional Sequencing81400, 81407, 81408, 81479Second Allele Testing$575-$1,626 10-12 weeksConventional Sequencing81400, 81407, 81408, 81479ABHD12, CDH23, CIB2, CLRN1, DFNB31, GPR98, HARS, MYO7A, PCDH15, USH1C, USH1G & USH2AExome Testing$220014-16 weeksAllele-Specific Testing Followed by Conventional Sequencing and Next Generation Sequencing81400, 81407, 81408, 81479X-Linked Familial Exudative Vitreoretinopathy (XL-FEVR) X-Linked NDP (full coding region) $121 8-12 weeks Conventional Sequencing 81479

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Genetic Tests Offered (all nonprofit) | The John and ...

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Renewed Vitality – Hormone Replacement Therapy Clinic

Thyroid & BioIdentical Hormone Therapy

As men and women age, many experience a decline in hormones, effecting their energy level, weight, sex drive, mental functions, strength, and diminishing their quality of life. With bioidentical hormone replacement you can have more energy, better sleep, restored sex drive, improved mood and mental clarity, improved muscle tone and strength, relief from hot flashes and depression and it can be easier to lose excess weight.

Renewed Vitality doctors evaluate each patient to locate and address the root cause of their weight gain. The Vitality Diet is a medically supervised weight loss program and is one of the safest, easiest and most effective on the market to take excess weight off and keep it off. With no invasive injections or protocols, we can help with weight loss and weight maintenance. Look and feel better about yourself. (Individual Results Will Vary)

Renewed Vitality is an ideal choice to find relief from Chronic Fatigue, Fibromyalgia, Chronic Viral Syndromes and many other illnesses that cause chronic pain and fatigue. These syndromes are not a mystery and can be treated. Patients at Renewed Vitality medical clinic enjoy a healing experience unlike anything they have ever known before. With effective treatment you can get your life back and experience renewed energy and vitality.

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Renewed Vitality - Hormone Replacement Therapy Clinic

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The addition of human iPS cell-derived neural progenitors …

JavaScript is disabled on your browser. Please enable JavaScript to use all the features on this page.Highlights

Human iPS cell-derived neural progenitors influence the contractile property of cardiac spheroid.

The contractile function of spheroids depends on the ratio of neural progenitors to cardiac cells.

Neural factors may influence the contractile function of the spheroids.

We havebeen attempting to use cardiac spheroids to construct three-dimensional contractilestructures for failed hearts. Recent studies have reported that neuralprogenitors (NPs) play significant roles in heart regeneration. However, theeffect of NPs on the cardiac spheroid has not yet been elucidated.

This studyaims to demonstrate the influence of NPs on the function of cardiac spheroids.

Thespheroids were constructed on a low-attachment-well plate by mixing humaninduced pluripotent stem (hiPS) cell-derived cardiomyocytes and hiPScell-derived NPs (hiPS-NPs). The ratio of hiPS-NPs was set at 0%, 10%, 20%,30%, and 40% of the total cell number of spheroids, which was 2500. The motionwas recorded, and the fractional shortening and the contraction velocity weremeasured.

Spheroidswere formed within 48 h after mixing the cells, except for the spheroidscontaining 0% hiPS-NPs. Observation at day 7 revealed significant differencesin the fractional shortening (analysis of variance; p=0.01). The bestfractional shortening was observed with the spheroids containing 30% hiPS-NPs.Neuronal cells were detected morphologically within the spheroids under aconfocal microscope.

Theaddition of hiPS-NPs influenced the contractile function of the cardiacspheroids. Further studies are warranted to elucidate the underlying mechanism.

Human iPS cell


Neural progenitor


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2018 Elsevier Ltd. All rights reserved.

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iPS Cells for Disease Modeling and Drug Discovery

Cambridge Healthtech Institutes 4th AnnualJune 19-20, 2019

With advances in reprogramming and differentiation technologies, as well as with the recent availability of gene editing approaches, we are finally able to create more complex and phenotypically accurate cellular models based on pluripotent cell technology. This opens new and exciting opportunities for pluripotent stem cell utilization in early discovery, preclinical and translational research. CNS diseases and disorders are currently the main therapeutic area of application with some impressive success stories resulted in clinical trials. Cambridge Healthtech Institutes 4th Annual iPS Cells for Disease Modeling and Drug Discovery conference is designed to bring together experts and bench scientists working with pluripotent cells and end users of their services, researchers working on finding cures for specific diseases and disorders.

Day 1 | Day 2 | Download Brochure | Speaker Biographies

Wednesday, June 19

12:00 pm Registration Open

12:00 Bridging Luncheon Presentation:Structural Maturation in the Development of hiPSC-Cardiomyocyte Models for Pre-clinical Safety, Efficacy, and Discovery

Nicholas Geissse, PhD, CSO, NanoSurface Biomedical

Alec S.T. Smith, PhD, Acting Instructor, Bioengineering, University of Washington

hiPSC-CM maturation is sensitive to structural cues from the extracellular matrix (ECM). Failure to reproduce these signals in vitro can hamper experimental reproducibility and fidelity. Engineering approaches that address this gap typically trade off complexity with throughput, making them difficult to deploy in the modern drug development paradigm. The NanoSurface Car(ina) platform leverages ECM engineering approaches that are fully compatible with industry-standard instrumentation including HCI- and MEA-based assays, thereby improving their predictive power.

12:30 Transition to Plenary


2:20Booth Crawl and Dessert Break in the Exhibit Hall with Poster Viewing

2:25 Meet the Plenary Keynotes

3:05 Chairpersons Remarks

Gabriele Proetzel, PhD, Director, Neuroscience Drug Discovery, Takeda Pharmaceuticals, Inc.

3:10 KEYNOTE PRESENTATION: iPSC-Based Drug Discovery Platform for Targeting Innate Immune Cell Responses

Christoph Patsch, PhD, Team Lead Stem Cell Assays, Disease Relevant Cell Models and Assays, Chemical Biology, Therapeutic Modalities, Roche Pharma Research and Early Development

The role of innate immune cells in health and disease, respectively their function in maintaining immune homeostasis and triggering inflammation makes them a prime target for therapeutic approaches. In order to explore novel therapeutic strategies to enhance immunoregulatory functions, we developed an iPSC-based cellular drug discovery platform. Here we will highlight the unique opportunities provided by an iPSC-based drug discovery platform for targeting innate immune cells.

3:40 Phenotypic Screening of Induced Pluripotent Stem Cell Derived Cardiomyocytes for Drug Discovery and Toxicity Screening

Arne Bruyneel, PhD, Postdoctoral Fellow, Mark Mercola Lab, Cardiovascular Institute, Stanford University School of Medicine

Cardiac arrhythmia and myopathy is a major problem with cancer therapeutics, including newer small molecule kinase inhibitors, and frequently causes heart failure, morbidity and death. However, currentin vitromodels are unable to predict cardiotoxicity, or are not scalable to aid drug development. However, with recent progress in human stem cell biology, cardiac differentiation protocols, and high throughput screening, new tools are available to overcome this barrier to progress.

4:10 Disease Modeling Using Human iPSC-Derived Telencephalic Inhibitory Interneurons - A Couple of Case Studies

Yishan Sun, PhD, Investigator, Novartis Institutes for BioMedical Research (NIBR)

Human iPSC-derived neurons provide the foundation for phenotypic assays assessing genetic or pharmacological effects in a human neurobiological context. The onus is on assay developers to generate application-relevant neuronal cell types from iPSCs, which is not always straightforward, given the diversity of neuronal classes in the human brain and their developmental trajectories. Here we present two case studies to illustrate the use of iPSC-derived telencephalic GABAergic interneurons in neuropsychiatric research.

4:40 Rethinking the Translational The Use of Highly Predictive hiPSC-Derived Models in Pre-Clinical Drug Development

Stefan Braam, CEO, Ncardia

Current drug development strategies are failing to increase the number of drugs reaching the market. One reason for low success rates is the lack of predictive models. Join our talk to learn how to implement a predictive and translational in vitro disease model, and assays for efficacy screening at any throughput.

5:10 4th of July Celebration in the Exhibit Hall with Poster Viewing

5:30 - 5:45 Speed Networking: Oncology

6:05 Close of Day

5:45 Dinner Short Course Registration

6:15 Dinner Short Course*

*Separate registration required.

Day 1 | Day 2 | Download Brochure | Speaker Biographies

Thursday, June 20

7:15 am Registration

7:15 Breakout Discussion Groups with Continental Breakfast

8:10 Chairpersons Remarks

Jeff Willy, PhD, Research Fellow, Discovery and Investigative Toxicology, Vertex

8:15 Levering iPSC to Understand Mechanism of Toxicity

Jeff Willy, PhD, Research Fellow, Discovery and Investigative Toxicology, Vertex

The discovery of mammalian cardiac progenitor cells suggests that the heart consists of not only terminally differentiated beating cardiomyocytes, but also a population of self-renewing stem cells. We recently showed that iPSC cardiomyocytes can be utilized not only to de-risk compounds with potential for adverse cardiac events, but also to understand underlying mechanisms of cell-specific toxicities following xenobiotic stress, thus preventing differentiation and self-renewal of damaged cells.

8:45Pluripotent Stem Cell-Derived Cardiac and Vascular Progenitor Cells for Tissue Regeneration

Nutan Prasain, PhD, Associate Director, Cardiovascular Programs, Astellas Institute for Regenerative Medicine (AIRM)

This presentation will provide the review on recent discoveries in the derivation and characterization of cardiac and vascular progenitor cells from pluripotent stem cells, and discuss the therapeutic potential of these cells in cardiac and vascular tissue repair and regeneration.

9:15 Use of iPSCDerived Hepatocytes to Identify Treatments for Liver Disease

Stephen A. Duncan, PhD, Smartstate Chair in Regenerative Medicine, Professor and Chairman, Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina

MTDPS3 is a rare disease caused by mutations in the DGUOK gene, which is needed for mitochondrial DNA (mtDNA) replication and repair. Patients commonly die as children from liver failure primarily caused by unmet energy requirements. We modeled the disease using DGOUK deficient iPSC derived hepatocytes and performed a screen to identify drugs that can restore mitochondrial ATP production.

9:45Industrial-Scale Generation of Human iPSC-Derived Hepatocytes for Liver-Disease and Drug Development Studies

Liz Quinn, PhD, Associate Director, Stem Cell Marketing, Marketing, Takara Bio USA

Our optimized hepatocyte differentiation protocol and standardized workflow mimics embryonic development and allows for highly efficient differentiation of hPSCs through definitive endoderm into hepatocytes. We will describe the creation of large panels of industrial-scale hPSC-derived hepatocytes with specific genotypes and phenotypes and their utility for drug metabolism and disease modeling.

10:00 Sponsored Presentation (Opportunity Available)

10:15 Coffee Break in the Exhibit Hall with Poster Viewing

10:45 Poster Winner Announced

11:00 KEYNOTE PRESENTATION: Modeling Human Disease Using Pluripotent Stem Cells

Lorenz Studer, MD, Director, Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center

One of the most intriguing applications of human pluripotent stem cells is the possibility of recreating a disease in a dish and to use such cell-based models for drug discovery. Our lab uses human iPS and ES cells for modeling both neurodevelopmental and neurodegenerative disorders. I will present new data on our efforts of modeling complex genetic disease using pluripotent stem cells and the development of multiplex culture systems.

11:30 Preclinical Challenges for Gene Therapy Approaches in Neuroscience

Gabriele Proetzel, PhD, Director, Neuroscience Drug Discovery, Takeda Pharmaceuticals, Inc.

Gene therapy has delivered encouraging results in the clinic, and with the first FDA approval for an AAV product is now becoming a reality. This presentation will provide an overview of the most recent advances of gene therapy for the treatment of neurological diseases. The discussion will focus on preclinical considerations for gene therapy including delivery, efficacy, biodistribution, animal models and safety.

12:00 pm Open Science Meets Stem Cells: A New Drug Discovery Approach for Neurodegenerative Disorders

Thomas Durcan, PhD, Assistant Professor, Neurology and Neurosurgery, McGill University

Advances in stem cell technology have provided researchers with tools to generate human neurons and develop first-of-their-kind disease-relevant assays. However, it is imperative that we accelerate discoveries from the bench to the clinic and the Montreal Neurological Institute (MNI) and its partners are piloting an Open Science model. By removing the obstacles in distributing patient samples and assay results, our goal is to accelerate translational medical research.

12:30 Elevating Drug Discovery with Advanced Physiologically Relevant Human iPSC-Based Screening Platforms

Fabian Zanella, PhD, Director, Research and Development, StemoniX

Structurally engineered human induced pluripotent stem cell (hiPSC)-based platforms enable greater physiological relevance, elevating performance in toxicity and discovery studies. StemoniXs hiPSC-derived platforms comprise neural (microBrain) or cardiac (microHeart) cells constructed with appropriate inter- and intracellular organization promoting robust activity and expected responses to known cellular modulators.

1:00Overcoming Challenges in CNS Drug Discovery through Developing Translatable iPSC-derived Cell-Based Assays

Jonathan Davila, PhD, CEO, Co-Founder, NeuCyte Inc.

Using direct reprogramming of iPSCs to generate defined human neural tissue, NeuCyte developed cell-based assays with complex neuronal structure and function readouts for versatile pre-clinical applications. Focusing on electrophysiological measurements, we demonstrate the capability of this approach to identify adverse neuroactive effects, evaluate compound efficacy, and serve phenotypic drug discovery.

1:15Enjoy Lunch on Your Own

1:35 Dessert and Coffee Break in the Exhibit Hall with Poster Viewing

1:45 - 2:00 Speed Networking: Last Chance to Meet with Potential Partners and Collaborators!

2:20 Chairpersons Remarks

Gary Gintant, PhD, Senior Research Fellow, AbbVie

2:25 The Evolving Roles of Evolving Human Stem Cell-Derived Cardiomyocyte Preparations in Cardiac Safety Evaluations

Gary Gintant, PhD, Senior Research Fellow, AbbVie

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for preclinical cardiac safety testing. Recent applications focus on drug effects on cardiac electrophysiology, contractility, and structural toxicities, with further complexity provided by the growing number of hiPSC-CM preparations being developed that may also promote myocyte maturity. The evolving roles (both non-regulatory and regulatory) of these preparations will be reviewed, along with general considerations for their use in cardiac safety evaluations.

2:55 Pharmacogenomic Prediction of Drug-Induced Cardiotoxicity Using hiPSC-Derived Cardiomyocytes

Paul W. Burridge, PhD, Assistant Professor, Department of Pharmacology, Center for Pharmacogenomics, Northwestern University Feinberg School of Medicine

We have demonstrated that human induced pluripotent stem cell-derived cardiomyocytes successfully recapitulate a patients predisposition to chemotherapy-induced cardiotoxicity, confirming that there is a genomic basis for this phenomenon. Here we will discuss our recent work deciphering the pharmacogenomics behind this relationship, allowing the genomic prediction of which patients are likely to experience this side effect. Our efforts to discover new drugs to prevent doxorubicin-induced cardiotoxicity will also be reviewed.

3:25 Exploring the Utility of iPSC-Derived 3D Cortical Spheroids in the Detection of CNS Toxicity

Qin Wang, PhD, Scientist, Drug Safety Research and Evaluation, Takeda

Drug-induced Central Nervous System (CNS) toxicity is a common safety attrition for project failure during discovery and development phases due low concordance rates between animal models and human, absence of clear biomarkers, and a lack of predictive assays. To address the challenge, we validated a high throughput human iPSC-derived 3D microBrain model with a diverse set of pharmaceuticals. We measured drug-induced changes in neuronal viability and Ca channel function. MicroBrain exposure and analyses were rooted in therapeutic exposure to predict clinical drug-induced seizures and/or neurodegeneration. We found that this high throughput model has very low false positive rate in the prediction of drug-induced neurotoxicity.

3:55 Linking Liver-on-a-Chip and Blood-Brain-Barrier-on-a-Chip for Toxicity Assessment

Sophie Lelievre, DVM, PhD, LLM, Professor, Cancer Pharmacology, Purdue University College of Veterinary Medicine

One of the challenges to reproduce the function of tissues in vitro is the maintenance of differentiation. Essential aspects necessary for such endeavor involve good mechanical and chemical mimicry of the microenvironment. I will present examples of the management of the cellular microenvironment for liver and blood-brain-barrier tissue chips and discuss how on-a-chip devices may be linked for the integrated study of the toxicity of drugs and other molecules.

4:25 Close of Conference

Day 1 | Day 2 | Download Brochure | Speaker Biographies

Arrive early to attend Tuesday, June 18 - Wednesday, June 19

Chemical Biology and Target Validation

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iPS Cells for Disease Modeling and Drug Discovery

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Heart Disease A Closer Look at Stem Cells

Overview of current stem cell-based approaches to treat heart disease

Since heart failure after heart attacks results from death of heart muscle cells, researchers have been developing strategies to remuscularize the damaged heart wall in efforts to improve its function. Researchers are transplanting different types of stem cell and progenitor cells (see above) into patients to repair the damaged heart muscle. These strategies have mainly used either adult stem cells (found in bone marrow, fat, or the heart itself) or pluripotent (ES or iPS) cells.

Preliminary results from experiments with adult stem cells showed that they appeared to improve cardiac function even though they died shortly after transplantation. This led to the idea that these cells can release signals that can improve function without replacing the lost muscle. Clinical trials began in the early 2000s transplanting adult stem cells from the bone marrow and then from the heart. These trials demonstrated that transplanting cells into damaged hearts is feasible and generally safe for patients. However, larger trials that were randomized, blinded, and placebo-controlled, showed fewer indications of improved function. The consensus now is that adult stem cells have modest, if any, benefit to cardiac function.

Research shows that pluripotent stem cell-derived cardiomyocytes can form beating human heart muscle cells that both release the necessary signals and replace muscle lost to heart attack. Transplantation of pluripotent stem cell-derived cardiac cells have demonstrated substantial benefits to cardiac function in animal models of heart disease, from mice to monkeys. Recently, pluripotent stem cell-derived interventions were used in clinical trials for the first time. Patches of human heart muscle cells derived from the stem cells were transplanted onto the surface of failing hearts. Early results suggest that this approach is feasible and safe, but it is too early to know whether there are functional benefits.Research is ongoing to test cellular therapies to treat heart attacks by combining different types of stem cells, repeating transplantations, or improving stem cell patches. Clinical trials using these improved methods are currently targeted to begin around 2020.Unfortunately, many unscrupulous clinics are making unsubstantiated claims about the efficacy of stem cell therapies for heart failure, creating confusion about the current state of cellular approaches for heart failure. To learn more about warning signs of these unproven interventions, please visit Nine Things to Know About Stem Cell Treatments.

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Heart Disease A Closer Look at Stem Cells

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Preconditioning of bone marrow-derived mesenchymal stem …

JavaScript is disabled on your browser. Please enable JavaScript to use all the features on this page.Abstract

Oxidative stress on transplanted bone marrow-derived mesenchymal stem cells (BMSCs) during acute inflammation is a critical issue in cell therapies. N-acetyl-L cysteine (NAC) promotes the production of a cellular antioxidant molecule, glutathione (GSH). The aim of this study was to investigate the effects of pre-treatment with NAC on the apoptosis resistance and bone regeneration capability of BMSCs. Rat femur-derived BMSCs were treated in growth medium with or without 5mM NAC for 6h, followed by exposure to 100MH2O2 for 24h to induce oxidative stress. Pre-treatment with NAC significantly increased intracellular GSH levels by up to two fold and prevented H2O2-induced intracellular redox imbalance, apoptosis and senescence. When critical-sized rat femur defects were filled with a collagen sponge containing fluorescent-labeled autologous BMSCs with or without NAC treatment, the number of apoptotic and surviving cells in the transplanted site after 3 days was significantly lower and higher in the NAC pre-treated group, respectively. By the 5th week, significantly enhanced new bone formation was observed in the NAC pre-treated group. These data suggest that pre-treatment of BMSCs with NAC before local transplantation enhances bone regeneration via reinforced resistance to oxidative stress-induced apoptosis at the transplanted site.

Acute inflammation


Cell conditioning


Local transplantation


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2018 Elsevier Ltd. All rights reserved.

Preconditioning of bone marrow-derived mesenchymal stem ...

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Genetic factors and hormones that determine gender

In the nucleus of every cell of his or her body, a human being has 46 chromosomes. 22 chromosome pairs (numbered from 1-22) belong to the autosomes and 1 pair to the sex chromosomes or gonosomes. They are denoted as X and Y. A female has two X-chromosomes and a male an X and a Y-chromosome. In a woman, one of the two X-chromosomes is inactivated in the form of heterochromatin (sex chromatin), the Barr body - diagnosis of the genetic gender is made on this basis. This inactivation already takes place in the blastocyst stage 3 - randomly - either on the paternal or maternal X chromosome. When a Y chromosome is present, the development takes place in the direction of manhood; if it is missing, a feminine development occurs.

It is not the number of gonosomes that is decisive for the gender, but rather the presence or absence of the Y-chromosome, as can be seen in the following table.


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An aneuploidy (anomaly in the number of chromosomes) of the gonosomes (sex chromosomes) is not rare, whereby Klinefelter's syndrome and Turner'ssyndromes occur the most frequently.Klinefelter's syndromeandTurner's syndrome

It is clear that the information encoded on the Y-chromosome is not enough to guide the formation of such a complicated organ as the testicles, but a localized gene on this chromosome, the SRY (sex determining region Y gene) operates very early in the development as a guide or "master gene". It has a testis-determining effect on the indifferent gonads. This small gene (a single exon), which is localized on the shorter arm of the Y chromosome (Yp), gets expressed in the precursors for the supporting cells (Sertoli). It controls a whole number of further genes on the autosomes as well as on the X chromosome. It is only through the concerted workings of this SRY-gene together with genes on other chromosomes that the development of the testicles is possible. (Diagram of the molecular factors involved in the development of the genital apparatus)

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Special case of a dissociation between the karyotype and phenotype.

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Genetic factors and hormones that determine gender

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Acute Hypopituitarism: Overview, Diagnostic Considerations …

Adrenocorticotropic hormone deficiency

A deficiency of adrenocorticotropic hormone (ACTH), or corticotropin, is characterized by a decrease in adrenal androgens and production of cortisol. Acute loss of adrenal function is a medical emergency and may lead to hypotension and death if not treated.

Signs and symptoms of ACTH deficiency may be profound and potentially fatal; they include myalgias, arthralgias, fatigue, headache, weight loss, anorexia, nausea, vomiting, abdominal pain, altered mentation or altered consciousness, dry wrinkled skin, decreased axillary and pubic hair, anemia of chronic disease, dilutional hyponatremia, hypoglycemia, hypotension, and shock.

Symptoms are nearly identical to those of primary adrenal insufficiency but can be differentiated by lack of hyperpigmentation. Hyperpigmentation occurs in a long feedback loop in which a cortisol deficiency results in increased production of ACTH by the pituitary. The ACTH precursor coupled to melanocyte-stimulating hormone is not produced in patients with pituitary disease, and therefore, hyperpigmentation does not take place.

Patients with secondary adrenal insufficiency usually are eukalemic. This differs from primary adrenal insufficiency, in which patients develop hyponatremia and hyperkalemia. Aldosterone secretion is not affected, as it does not depend on corticotropin but instead on the renin-angiotensin axis.

Secondary hypothyroidism due to decreased TSH (also known as thyrotropin) exhibits symptoms identical to those of primary thyroid disease, only typically less severe. Signs and symptoms of secondary hypothyroidism include fatigue, weakness, weight gain, thickened subcutaneous tissues, constipation, cold intolerance, altered mental status, impaired memory, and anemia. Physical examination of the patient may reveal bradycardia, delayed relaxation of the deep tendon reflexes, and periorbital edema.

Low levels of the gonadotropins--follicle-stimulating hormone (FSH) and luteinizing hormone (LH) --increase the risk of osteoporosis due to decreased bone density and result in hypogonadism in men and women. In men, symptoms include decreased libido, varying degrees of erectile dysfunction, decreased ejaculate, muscle weakness, and fatigue. Men with long-standing hypogonadism have decreased hair growth, soft testes, and gynecomastia.

Patients may be anemic due to decreased erythropoietin production, which causes a normochromic, normocytic anemia. Pubic and axillary hair growth is usually normal unless a concomitant ACTH deficiency exists.

Premenopausal women present with altered menstrual function, ranging from regular anovulatory periods to amenorrhea, as well as hot flashes, decreased libido, breast atrophy, vaginal dryness, and dyspareunia. Postmenopausal women usually present with headache or visual abnormalities due to other hormonal deficiencies or mass lesions.

In children, FSH and LH deficiency can cause eunuchoidism and lack of sexual development. FSH and LH have an indirect effect on bone growth by causing closure of the epiphysis. Characteristics of eunuchoidism are due to delay in closure of the epiphysis, resulting in long extremities.

In children, growth hormone (GH) deficiency presents as growth retardation and delayed sexual maturation. Patients may present with fasting hypoglycemia due to loss of the gluconeogenic effect of GH, which counteracts the effect of insulin. In adults, GH deficiency presents as weakness, poor wound healing, decreased exercise tolerance, and decreased social functioning.

Tumor growth that decreases prolactin (PRL) production affects the process of lactation; these tumors become evident only in the postpartum state. PRL deficiency is very rare; any process that affects the hypothalamus and the pituitary stalk decreases the normal inhibitory effect of dopamine from the hypothalamus on the pituitary, causing a rebound increase in PRL.

Antidiuretic hormone (ADH) deficiency causes polyuria and polydipsia (diabetes insipidus). When deficient in ADH (also known as vasopressin), the distal tubules of the kidney are unable to absorb water, producing very dilute urine and increasing serum osmolality. If water excretion exceeds oral intake, a patient may become hypotensive and hypovolemic, with hypernatremia and elevated serum osmolality. If fluid intake matches fluid output, serum sodium and osmolality may remain normal.

Central diabetes insipidus is caused by a decrease in ADH secretion, in contrast to nephrogenic diabetes insipidus, in which the kidney is ADH resistant.

Deficiency in oxytocin is characterized by a decrease in milk ejection during lactation. Interestingly, women with known oxytocin deficiency undergo normal labor and delivery despite the lack of hormone. One of the initial clues to the presence of Sheehan syndrome should be the lack of lactation secondary to oxytocin deficiency.

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Bone marrow mesenchymal stem cells: Aging and tissue …

JavaScript is disabled on your browser. Please enable JavaScript to use all the features on this page.Abstract

Bone has well documented natural healing capacity that normally is sufficient to repair fractures and other common injuries. However, the properties of bone change throughout life, and aging is accompanied by increased incidence of bone diseases and compromised fracture healing capacity, which necessitate effective therapies capable of enhancing bone regeneration. The therapeutic potential of adult mesenchymal stem cells (MSCs) for bone repair has been long proposed and examined. Actions of MSCs may include direct differentiation to become bone cells, attraction and recruitment of other cells, or creation of a regenerative environment via production of trophic growth factors. With systemic aging, MSCs also undergo functional decline, which has been well investigated in a number of recent studies. In this review, we first describe the changes in MSCs during aging and discuss how these alterations can affect bone regeneration. We next review current research findings on bone tissue engineering, which is considered a promising and viable therapeutic solution for structural and functional restoration of bone. In particular, the importance of MSCs and bioscaffolds is highlighted. Finally, potential approaches for the prevention of MSC aging and the rejuvenation of aged MSC are discussed.



Stem cell niche

Bone healing


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2018 Published by Elsevier Ltd.

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Stem Cells for Skin Quality –

Stem cells can do a lot of things - they can heal damaged tissue, reduce inflammation and restore function to damaged tissues. Did you know that stem cells can also improve your skin's quality and reduce the signs of aging? Innovations Stem Cell Center offers fat stem cell therapy for not only a wide array of medical conditions, but also for powerful anti-aging benefits.

How Can Stem Cell Therapy Improve Skin Quality?

Stem cells can help improve skin quality by helping to heal tissues that have been damaged by:

Aging. The aging process causes the breakdown of skin cells and skin quality, leaving the skin looking dull and dirty. Skin also loses elasticity and tightness.

Genetics. Genetics plays a large part in how your skin ages, and it's hard to fight it with over-the-counter products and treatments.

Poor diet. Lack of quality nutrition can negatively impact both the body and the skin. When the skin is not supported through a healthy diet, skin becomes dull, drab and damaged.

Environment. Environmental factors that affect the skin include pollution, dirt and germs. These things clog the pores, dull your appearance and lead to blemishes, acne and breakouts. Environmental factors also include prolonged exposure to the sun, which can cause pigmentation problems and destroy collagen and elastin.

How Is Stem Cell Therapy Used for the Skin?

One of the ways stem cell therapy is used for the skin is through a stem cell face-lift procedure. During this treatment, Dr. Johnson harvests stem cells from unwanted fat taken from another area of your body, such as your lower back or abdomen.

After the cells are harvested, they are separated from the blood and other tissue and then injected into your face with tiny needles.

The stem cell face-lift can be combined with other procedures, such as the facial fat transfer. Combining the procedures increases the odds of stem cell survival and boosts the anti-aging benefits.

What Are the Benefits of Stem Cell Therapy for the Skin?

Patients who undergo stem cell therapy for anti-aging benefits see changes in their skin such as:

Are you interested in learning more about stem cell therapy and its benefits for your skin? Call Innovations Stem Cell today at 214-256-1462 to learn more.

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CloneR hPSC Cloning Supplement – Stemcell Technologies

'); jQuery('.cart-remove-box a').on('click', function(){ link = jQuery(this).attr('href'); jQuery.ajax({ url: link, cache: false }); jQuery('.cart-remove-box').remove(); setTimeout(function(){window.location.reload();}, 800); }); }); //jQuery('#ajax_loader').hide(); // clear being added addToCartButton.text(defaultText).removeAttr('disabled').removeClass('disabled'); addToCartButton.parent().find('.disabled-blocker').remove(); loadingDots.remove(); clearInterval(loadingDotId); jQuery('body').append(""); setTimeout(function () {jQuery('.add-to-cart-success').slideUp(500)}, 5000); }); } try { jQuery.ajax( { url : url, dataType : 'json', type : 'post', data : data, complete: function(){ if(jQuery('body').hasClass('product-edit') || jQuery('body').hasClass('wishlist-index-configure')){ jQuery.ajax({ url: "", cache: false }).done(function(html){ jQuery('header#header .top-cart').replaceWith(html); }); jQuery('#ajax_loader').hide(); jQuery('body').append(""); setTimeout(function () {jQuery('.add-to-cart-success').slideUp(500)}, 5000); } }, success : function(data) { if(data.status == 'ERROR'){ jQuery('body').append(''); }else{ ajaxComplete(); } } }); } catch (e) { } // End of our new ajax code this.form.action = oldUrl; if (e) { throw e; } } }.bind(productAddToCartForm); productAddToCartForm.submitLight = function(button, url){ if(this.validator) { var nv = Validation.methods; delete Validation.methods['required-entry']; delete Validation.methods['validate-one-required']; delete Validation.methods['validate-one-required-by-name']; if (this.validator.validate()) { if (url) { this.form.action = url; } this.form.submit(); } Object.extend(Validation.methods, nv); } }.bind(productAddToCartForm); function setAjaxData(data,iframe,name,image){ if(data.status == 'ERROR'){ jQuery('body').append(''); }else{ if(data.sidebar && !iframe){ if(jQuery('.top-cart').length){ jQuery('.top-cart').replaceWith(data.sidebar); } if(jQuery('.sidebar .block.block-cart').length){ if(jQuery('#cart-sidebar').length){ jQuery('#cart-sidebar').html(jQuery(data.sidebar).find('#mini-cart')); jQuery('.sidebar .block.block-cart .subtotal').html(jQuery(data.sidebar).find('.subtotal')); }else{ jQuery('.sidebar .block.block-cart p.empty').remove(); content = jQuery('.sidebar .block.block-cart .block-content'); jQuery('').appendTo(content); jQuery('').appendTo(content); content.find('#cart-sidebar').html(jQuery(data.sidebar).find('#mini-cart').html()); content.find('.actions').append(jQuery(data.sidebar).find('.subtotal')); content.find('.actions').append(jQuery(data.sidebar).find('.actions button.button')); } cartProductRemove('#cart-sidebar li.item a.btn-remove', { confirm: 'Are you sure you would like to remove this item from the shopping cart?', submit: 'Ok', calcel: 'Cancel' }); } jQuery.fancybox.close(); jQuery('body').append(''); }else{ jQuery.ajax({ url: "", cache: false }).done(function(html){ jQuery('header#header .top-cart').replaceWith(html); jQuery('.top-cart #mini-cart li.item a.btn-remove').on('click', function(event){ event.preventDefault(); jQuery('body').append('Are you sure you would like to remove this item from the shopping cart?OkCancel'); jQuery('.cart-remove-box a').on('click', function(){ link = jQuery(this).attr('href'); jQuery.ajax({ url: link, cache: false }); jQuery('.cart-remove-box').remove(); setTimeout(function(){window.location.reload();}, 800); }); }); jQuery.fancybox.close(); jQuery('body').append(''); }); } } setTimeout(function () {jQuery('.add-to-cart-success').slideUp(500)}, 5000); } //]]> CloneR is a defined, serum-free supplement designed to increase the cloning efficiency and single-cell survival of human embryonic stem cells (ES cells) and induced pluripotent stem cells (iPS cells). CloneR enables the robust generation of clonal cell lines without single-cell adaptation, thus minimizing the risk of acquiring genetic abnormalities.

CloneR is compatible with the TeSR family of media for human ES and iPS cell maintenance as well as your choice of cell culture matrix.


Greatly facilitates the process of genome editing of human ES and iPS cells Compatible with any TeSR maintenance medium and your choice of cell culture matrix Does not require adaptation to single-cell passaging Increases single-cell survival at clonal density across multiple human ES and iPS cell lines

Cell Type:

Pluripotent Stem Cells


Cell Culture

Area of Interest:

Cell Line Development; Stem Cell Biology; Disease Modeling


Defined; Serum-Free

Document Type

Product Name

Catalog #

Lot #


This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.

Research Area Workflow Stages for

Workflow Stages

Figure 1. hPSC Single-Cell Cloning Workflow with CloneR

On day 0, human pluripotent stem cells (hPSCs) are seeded as single cells at clonal density (e.g. 25 cells/cm2) or sorted at 1 cell per well in 96-well plates in TeSR (mTeSR1 or TeSR-E8) medium supplemented with CloneR. On day 2, the cells are fed with TeSR medium containing CloneR supplement. From day 4, cells are maintained in TeSR medium without CloneR. Colonies are ready to be picked between days 10 - 14. Clonal cell lines can be maintained long-term in TeSR medium.

Figure 2. CloneR Increases the Cloning Efficiency of hPSCs and is Compatible with Multiple hPSC Lines and Seeding Protocols

TeSR medium supplemented with CloneR increases hPSC cloning efficiency compared with cells plated in TeSR containing ROCK inhibitor. Cells were seeded (A) at clonal density (25 cells/cm2) in mTeSR1 and TeSR-E8 and (B) by single-cell deposition using FACS (seeded at 1 cell/well) in mTeSR1.

Figure 3. CloneR Increases the Cloning Efficiency of hPSCs at Low Seeding Densities

hPSCs plated in mTeSR1 supplemented with CloneR demonstrated significantly increased cloning efficiencies compared to cells plated in mTeSR1 containing ROCK inhibitor (10M Y-27632). Shown are representative images of alkaline phosphatase-stained colonies at day 7 in individual wells of a 12-well plate. H1 human embryonic stem (hES) cells were seeded at clonal density (100 cells/well, 25 cells/cm2) in mTeSR1 supplemented with (A) ROCK inhibitor or (B) CloneR on Vitronectin XF cell culture matrix.

Figure 4. CloneR Yields Larger Single-Cell Derived Colonies

hPSCs seeded in mTeSR1 supplemented with CloneR result in larger colonies than cells seeded in mTeSR1 containing ROCK inhibitor (10M Y-27632). Shown are representative images of hPSC clones established after 7 days of culture in mTeSR1 supplemented with (A) ROCK inhibitor or (B) CloneR.

Figure 5. Clonal Cell Lines Established Using CloneR Display Characteristic hPSC Morphology

Clonal cell lines established using mTeSR1 or TeSR-E8 medium supplemented with CloneR retain the prominent nucleoli and high nuclear-to-cytoplasmic ratio characteristic of hPSCs. Representative images at passage 7 after cloning are shown for clones derived from the parental (A) H1 hES cell and (B) WLS-1C human induced pluripotent stem (iPS) cell lines.

Figure 6. Clonal Cell Lines Established with CloneR Express High Levels of Undifferentiated Cell Markers

hPSC clonal cell lines established using mTeSR1 supplemented with CloneR express comparable levels of undifferentiated cell markers, OCT4 (Catalog #60093) and TRA-1-60 (Catalog #60064), as the parental cell lines. (A) Clonal cell lines established from parental H1 hES cell line. (B) Clonal cell lines established from parental WLS-1C hiPS cell line. Data is presented between passages 5 - 7 after cloning and is shown as mean SEM; n = 2.

Figure 7. Clonal Cell Lines Established Using CloneR Display a Normal Karyotype

Representative karyograms of clones derived from parental (A) H1 hES cell and (B) WLS-1C hiPS cell lines demonstrate that the clonal lines established with CloneR have a normal karyotype. Cells were karyotyped 5 passages after cloning, with an overall passage number of 45 and 39, respectively.

Figure 8. Clonal Cell Lines Established Using CloneR Display Normal Growth Rates

Fold expansion of clonal cell lines display similar growth rates to parental cell lines. Shown are clones (red) and parental cell lines (gray) for (A) H1 hES cell and (B) WLS-1C hiPS cell lines.


Internal Search Keywords: genome editing | cloning | CRISPR | clone | gene editing | 05888 | 5888 | single cell | accutase

CloneR hPSC Cloning Supplement - Stemcell Technologies

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A Study to Evaluate the Efficacy and Safety of Factor IX … Identifier: NCT03861273 Recruitment Status : Not yet recruiting

First Posted : March 4, 2019

Last Update Posted : April 4, 2019


Information provided by (Responsible Party):


Brief Summary:

This study will evaluate the efficacy and safety of PF-06838435 (a gene therapy drug) in adult male participants with moderately severe to severe hemophilia B (participants that have a Factor IX circulating activity of 2% or less). The gene therapy is designed to introduce genetic material into cells to compensate for missing or non-functioning Factor IX. Eligible study participants will have completed a minimum 6 months of routine Factor IX prophylaxis therapy during the lead in study (C0371004). Participants will be dosed once (intravenously) and will be evaluated over the course of 6 years. The main objectives of the study are to compare the annualized bleeding rate [ABR] of the gene therapy to routine prophylaxis from the lead-in study and to evaluate the impact that it may have on participant's Factor IX circulating activity [FIX:C].

Gene Therapy

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Inclusion Criteria

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03861273


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A Study to Evaluate the Efficacy and Safety of Factor IX ...

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Female Genetic Contributions to Sperm Competition in …


In many species, sperm can remain viable in the reproductive tract of a female well beyond the typical interval to remating. This creates an opportunity for sperm from different males to compete for oocyte fertilization inside the female's reproductive tract. In Drosophila melanogaster, sperm characteristics and seminal fluid content affect male success in sperm competition. On the other hand, although genome-wide association studies (GWAS) have demonstrated that female genotype plays a role in sperm competition outcome as well, the biochemical, sensory and physiological processes by which females detect and selectively use sperm from different males remain elusive. Here, we functionally tested 26 candidate genes implicated via a GWAS for their contribution to the female's role in sperm competition, measured as changes in the relative success of the first male to mate (P1). Of these 26 candidates, we identified eight genes that affect P1 when knocked down in females, and showed that five of them do so when knocked down in the female nervous system. In particular, Rim knockdown in sensory pickpocket (ppk)+ neurons lowered P1, confirming previously published results, and a novel candidate, caup, lowered P1 when knocked down in octopaminergic Tdc2+ neurons. These results demonstrate that specific neurons in the female's nervous system play a functional role in sperm competition and expand our understanding of the genetic, neuronal and mechanistic basis of female responses to multiple matings. We propose that these neurons in females are used to sense and integrate signals from courtship or ejaculates, to modulate sperm competition outcome accordingly.

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Female Genetic Contributions to Sperm Competition in ...

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Success in Cryonics –

Despite the fact that no human placed in a cryonic suspension has yet been revived, some living organisms can be, and have been, brought back from a dead or near-dead state.

Many biological specimens, including whole insects, many types of human tissue including brain tissue, and human embryos have been cryogenically preserved, stored at liquid nitrogen temperature where all decay ceases, and revived. Cooling living cells to cryogenic temperatures slows metabolic process almost to a stop, making sure the cell doesn't use anymore energy, receive chemical signals, or to carry out any living processes. This would allow a cell to stay in its current state for any amount of time needed, until it is heated to normal functioning temperatures, where the body would continue its processes of life with freezing being a pause on life. This leads scientists to believe that the same can be done with whole human bodies, and that any minimal harm can be reversed with future advancements in medicine.

Neurosurgeons often cool patients bodies so they can operate on aneurysms without damaging or rupturing the nearby blood vessels. Human embryos that are frozen in fertility clinics, defrosted and implanted in a mothers uterus grow into perfectly normal human beings. This method isnt new or groundbreaking- successful cryopreservation of human embryos was first reported in 1983 by Trounson and Mohr with multicellular embryos that had been slow-cooled using dimethyl sulphoxide (DMSO).

Even though a mammal has not been fully frozen at cryogenic temperatures and revived, similar tests have been done on monkeys and dogs. The animals had their blood removed and the cryoprotectant inserted. The animals were then cooled to temperatures under 0 degrees Celsius and fully revived.

Some frogs and other amphibians have a protein manufactured by their cells that act as a natural antifreeze which can protect them if theyre frozen completely solid.

And just in Feb. of 2016, there was a cryonics breakthrough when for the first time, scientists vitrified a rabbits brain and, after warming it back up, showed that it was in near perfect condition. Problems with the brain are the main reason why people are skeptical about cryonics, yet the rabbit's brain retained all memory and learning ability. This was the first time a cryopreservation was provably able to protect everything associated with learning and memory.

Cryogenically preserved rabbit brain

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Success in Cryonics -

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Explainer: How CRISPR works | Science News for Students

(more about Power Words)

applicationA particular use or function of something.

base (in genetics) A shortened version of the term nucleobase. These bases are building blocks of DNA and RNA molecules.

biologyThe study of living things. The scientists who study them are known as biologists.

Cas9An enzyme that geneticists are now using to help edit genes. It can cut through DNA, allowing it to fix broken genes, splice in new ones or disable certain genes. Cas9 is shepherded to the place it is supposed to make cuts by CRISPRs, a type of genetic guides. The Cas9 enzyme came from bacteria. When viruses invade a bacterium, this enzyme can chop up the germs DNA, making it harmless.

cellThe smallest structural and functional unit of an organism. Typically too small to see with the naked eye, it consists of watery fluid surrounded by a membrane or wall. Animals are made of anywhere from thousands to trillions of cells, depending on their size. Some organisms, such as yeasts, molds, bacteria and some algae, are composed of only one cell.

chemicalA substance formed from two or more atoms that unite (become bonded together) in a fixed proportion and structure. For example, water is a chemical made of two hydrogen atoms bonded to one oxygen atom. Its chemical symbol is H2O.

CRISPRAn abbreviation pronounced crisper for the term clustered regularly interspaced short palindromic repeats. These are pieces of RNA, an information-carrying molecule. They are copied from the genetic material of viruses that infect bacteria. When a bacterium encounters a virus that it was previously exposed to, it produces an RNA copy of the CRISPR that contains that virus genetic information. The RNA then guides an enzyme, called Cas9, to cut up the virus and make it harmless. Scientists are now building their own versions of CRISPR RNAs. These lab-made RNAs guide the enzyme to cut specific genes in other organisms. Scientists use them, like a genetic scissors, to edit or alter specific genes so that they can then study how the gene works, repair damage to broken genes, insert new genes or disable harmful ones.

developmental(in biology) An adjective that refers to the changes an organism undergoes from conception through adulthood. Those changes often involve chemistry, size and sometimes even shape.

DNA(short for deoxyribonucleic acid) A long, double-stranded and spiral-shaped molecule inside most living cells that carries genetic instructions. It is built on a backbone of phosphorus, oxygen, and carbon atoms. In all living things, from plants and animals to microbes, these instructions tell cells which molecules to make.

engineeringThe field of research that uses math and science to solve practical problems.

fieldAn area of study, as in: Her field of research was biology. Also a term to describe a real-world environment in which some research is conducted, such as at sea, in a forest, on a mountaintop or on a city street. It is the opposite of an artificial setting, such as a research laboratory.

fluorescentCapable of absorbing and reemitting light. That reemitted light is known as a fluorescence.

gene(adj. genetic) A segment of DNA that codes, or holds instructions, for producing a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.

genomeThe complete set of genes or genetic material in a cell or an organism. The study of this genetic inheritance housed within cells is known as genomics.

muscleA type of tissue used to produce movement by contracting its cells, known as muscle fibers. Muscle is rich in a protein, which is why predatory species seek prey containing lots of this tissue.

mutation(v. mutate) Some change that occurs to a gene in an organisms DNA. Some mutations occur naturally. Others can be triggered by outside factors, such as pollution, radiation, medicines or something in the diet. A gene with this change is referred to as a mutant.

nucleusPlural is nuclei. (in biology) A dense structure present in many cells. Typically a single rounded structure encased within a membrane, the nucleus contains the genetic information.

organ(in biology) Various parts of an organism that perform one or more particular functions. For instance, an ovary is an organ that makes eggs, the brain is an organ that interprets nerve signals and a plants roots are organs that take in nutrients and moisture.

palindrome (adj. palindromic) A word, a name or a phrase that has the same ordering of letters when read forwards or backwards. For instance, dad and mom are both palindromes.

proteinCompoundmade from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. The hemoglobin in blood and the antibodies that attempt to fight infections are among the better-known, stand-alone proteins. Medicines frequently work by latching onto proteins.

RNAA molecule that helps read the genetic information contained in DNA. A cells molecular machinery reads DNA to create RNA, and then reads RNA to create proteins.

tag(in biology) To attach some rugged band or package of instruments onto an animal. Sometimes the tag is used to give each individual a unique identification number. Once attached to the leg, ear or other part of the body of a critter, it can effectively become the animals name. In some instances, a tag can collect information from the environment around the animal as well. This helps scientists understand both the environment and the animals role within it.

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Explainer: How CRISPR works | Science News for Students

Recommendation and review posted by Bethany Smith

Are Calico Cats Always Female? –

Many people are surprised to hear that the vast majority of calico cats are female. Why is this? Can a calico cat to ever be male? Learn more about the genetics of coat color in felines.

A calico cat is not a breed of cat, it is a color pattern. To be called "calico," three colors must be present: black, white, and orange. Variations of these colors include gray, cream, and ginger. A true calico cat has large blocks of these three colors. Other names for calico cats include tortoiseshell or "torties," brindle, or tricolor cats.

Calico cats areusually female. And, this is due in large part togenetics.Coat color is a complex process that is the result of dominant and non-dominate genes interacting within the X chromosomes. Since coat color is a sex-linked trait, it is one of the cat's physical traits that vary based on gender.

Female animals have two X chromosomes (XX), while males have one X chromosome and one Y chromosome (XY). The genetic coding for having black or orange color in thecoat is found in the X chromosome. The color display is either orange or black.The coding for white is a completely separate gene.

In femalemammals, one of the X chromosomes is randomly deactivated,called X-inactivation,in each cell.For calico cats, the random mix of color genes that are activated or deactivated gives the blotchy orange and black color display.

Since females have two X chromosomes, they are able to have two different colors (orange or black, depending what X was deactivated) and white; creating the three-color calico mix.

Since males have only one X chromosome, they only have one black or orange gene and can only display orange or black (plus or minus white, controlled by another gene).

Calico cats are not always female. Male calico cats do exist and typically have a chromosomal aberration of two X chromosomes and one Y chromosome (XXY). Cats with this chromosomal configuration are usually sterile,which means that they are not able to breed. This syndrome is similar to a condition in humans called Klinefelter's syndrome, or XXY syndrome.

On October 1, 2001, the calico cat became the official cat of the state of Maryland in the United States.Calico cats are believed to bringgood luckin the folklore of many cultures.Japanese sailors often had a calicoship's catto protect against misfortune at sea.

Cat genetics is responsible for producing many different varieties of cats and coat types. Common types include the bicolor or tuxedo cat (mostly black with a white chest), striped or marbled tabby cats, and solid color cats.

White cats, true albino cats, are quite rare. Much more common is the appearance of white coat color that is caused by a lack ofmelanocytes, or pigmentation cells, in the skin.White cats with one or two blue eyes have a particularly high likelihood of being deaf.

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Are Calico Cats Always Female? -

Recommendation and review posted by Bethany Smith

RNA targeting with CRISPRCas13 | Nature

Fire, A. et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806811 (1998)

Elbashir, S. M. et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494498 (2001)

Root, D. E., Hacohen, N., Hahn, W. C., Lander, E. S. & Sabatini, D. M. Genome-scale loss-of-function screening with a lentiviral RNAi library. Nat. Methods 3, 715719 (2006)

Jackson, A. L. et al. Expression profiling reveals off-target gene regulation by RNAi. Nat. Biotechnol. 21, 635637 (2003)

Tyagi, S. Imaging intracellular RNA distribution and dynamics in living cells. Nat. Methods 6, 331338 (2009)

Shmakov, S. et al. Diversity and evolution of class 2 CRISPRCas systems. Nat. Rev. Microbiol. 15, 169182 (2017)

Shmakov, S. et al. Discovery and functional characterization of diverse class 2 CRISPRCas systems. Mol. Cell 60, 385397 (2015)

Abudayyeh, O. O. et al. C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector. Science 353, aaf5573 (2016)

Gootenberg, J. S. et al. Nucleic acid detection with CRISPRCas13a/C2c2. Science 356, 438442 (2017)

Dahlman, J. E. et al. Orthogonal gene knockout and activation with a catalytically active Cas9 nuclease. Nat. Biotechnol. 33, 11591161 (2015)

Hutchinson, J. N. et al. A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. BMC Genomics 8, 39 (2007)

East-Seletsky, A. et al. Two distinct RNase activities of CRISPRC2c2 enable guide-RNA processing and RNA detection. Nature 538, 270273 (2016)

Zetsche, B. et al. Multiplex gene editing by CRISPRCpf1 using a single crRNA array. Nat. Biotechnol. 35, 3134 (2017)

Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 1554515550 (2005)

Rath, S. et al. Human RNase L tunes gene expression by selectively destabilizing the microRNA-regulated transcriptome. Proc. Natl Acad. Sci. USA 112, 1591615921 (2015)

Gross, G. G. et al. Recombinant probes for visualizing endogenous synaptic proteins in living neurons. Neuron 78, 971985 (2013)

Unsworth, H., Raguz, S., Edwards, H. J., Higgins, C. F. & Yage, E. mRNA escape from stress granule sequestration is dictated by localization to the endoplasmic reticulum. FASEB J. 24, 33703380 (2010)

Nelles, D. A. et al. Programmable RNA tracking in live cells with CRISPR/Cas9. Cell 165, 488496 (2016)

Tourrire, H. et al. The RasGAP-associated endoribonuclease G3BP assembles stress granules. J. Cell Biol. 160, 823831 (2003).

Tafer, H. et al. The impact of target site accessibility on the design of effective siRNAs. Nat. Biotechnol. 26, 578583 (2008)

Mann, D. G. et al. Gateway-compatible vectors for high-throughput gene functional analysis in switchgrass (Panicum virgatum L.) and other monocot species. Plant Biotechnol. J. 10, 226236 (2012)

Zhang, Y. et al. A highly efficient rice green tissue protoplast system for transient gene expression and studying light/chloroplast-related processes. Plant Methods 7, 30 (2011)

Joung, J. et al. Genome-scale CRISPRCas9 knockout and transcriptional activation screening. Nat. Protocols 12, 828863 (2017)

Jain, M., Nijhawan, A., Tyagi, A. K. & Khurana, J. P. Validation of housekeeping genes as internal control for studying gene expression in rice by quantitative real-time PCR. Biochem. Biophys. Res. Commun. 345, 646651 (2006)

Bernhart, S. H., Hofacker, I. L. & Stadler, P. F. Local RNA base pairing probabilities in large sequences. Bioinformatics 22, 614615 (2006)

Li, B. & Dewey, C. N. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics 12, 323 (2011)

Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676682 (2012)

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RNA targeting with CRISPRCas13 | Nature

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CRISPR Timeline | Broad Institute

Discovery of CRISPR and its function 1993 - 2005 Francisco Mojica, University of Alicante, Spain

Francisco Mojica was the first researcher to characterize what is now called a CRISPR locus, reported in 1993. He worked on them throughout the 1990s, and in 2000, he recognized that what had been reported as disparate repeat sequences actually shared a common set of features, now known to be hallmarks of CRISPR sequences (he coined the term CRISPR through correspondence with Ruud Jansen, who first used the term in print in 2002). In 2005 he reported that these sequences matched snippets from the genomes of bacteriophage (Mojica et al., 2005). This finding led him to hypothesize, correctly, that CRISPR is an adaptive immune system. Another group, working independently, published similar findings around this same time (Pourcel et al., 2005)

Discovery of Cas9 and PAMMay, 2005 Alexander Bolotin, French National Institute for Agricultural Research (INRA)

Bolotin was studying the bacteria Streptococcus thermophilus, which had just been sequenced, revealing an unusual CRISPR locus (Bolotin et al., 2005). Although the CRISPR array was similar to previously reported systems, it lacked some of the known cas genes and instead contained novel cas genes, including one encoding a large protein they predicted to have nuclease activity, which is now known as Cas9. Furthermore, they noted that the spacers, which have homology to viral genes, all share a common sequence at one end. This sequence, the protospacer adjacent motif (PAM), is required for target recognition.

Hypothetical scheme of adaptive immunityMarch, 2006 Eugene Koonin, US National Center for Biotechnology Information, NIH

Koonin was studying clusters of orthologous groups of proteins by computational analysis and proposed a hypothetical scheme for CRISPR cascades as bacterial immune system based on inserts homologous to phage DNA in the natural spacer array, abandoning previous hypothesis that the Cas proteins might comprise a novel DNA repair system.(Makarova et al., 2006)

Experimental demonstration of adaptive immunityMarch, 2007 Philippe Horvath, Danisco France SAS

S. thermophilus is widely used in the dairy industry to make yogurt and cheese, and scientists at Danisco wanted to explore how it responds to phage attack, a common problem in industrial yogurt making. Horvath and colleagues showed experimentally that CRISPR systems are indeed an adaptive immune system: they integrate new phage DNA into the CRISPR array, which allows them to fight off the next wave of attacking phage (Barrangou et al., 2007). Furthermore, they showed that Cas9 is likely the only protein required for interference, the process by which the CRISPR system inactivates invading phage, details of which were not yet known.

Spacer sequences are transcribed into guide RNAsAugust, 2008 John van der Oost, University of Wageningen, Netherlands

Scientists soon began to fill in some of the details on exactly how CRISPR-Cas systems interfere with invading phage. The first piece of critical information came from John van der Oost and colleagues who showed that in E-scherichia coli, spacer sequences, which are derived from phage, are transcribed into small RNAs, termed CRISPR RNAs (crRNAs), that guide Cas proteins to the target DNA (Brouns et al., 2008).

CRISPR acts on DNA targets December, 2008 Luciano Marraffini and Erik Sontheimer, Northwestern University, Illinois

The next key piece in understanding the mechanism of interference came from Marraffini and Sontheimer, who elegantly demonstrated that the target molecule is DNA, not RNA (Marraffini and Sontheimer, 2008). This was somewhat surprising, as many people had considered CRISPR to be a parallel to eukaryotic RNAi silencing mechanisms, which target RNA. Marraffini and Sontheimer explicitly noted in their paper that this system could be a powerful tool if it could be transferred to non-bacterial systems. (It should be noted, however, that a different type of CRISPR system can target RNA (Hale et al., 2009)).

Cas9 cleaves target DNADecember, 2010 Sylvain Moineau, University of Laval, Quebec City, Canada

Moineau and colleagues demonstrated that CRISPR-Cas9 creates double-stranded breaks in target DNA at precise positions, 3 nucleotides upstream of the PAM (Garneau et al., 2010). They also confirmed that Cas9 is the only protein required for cleavage in the CRISPR-Cas9 system. This is a distinguishing feature of Type II CRISPR systems, in which interference is mediated by a single large protein (here Cas9) in conjunction with crRNAs.

Discovery of tracrRNA for Cas9 systemMarch, 2011 Emmanuelle Charpentier, Umea University, Sweden and University of Vienna, Austria

The final piece to the puzzle in the mechanism of natural CRISPR-Cas9-guided interference came from the group of Emmanuelle Charpentier. They performed small RNA sequencing on Streptococcus pyogenes, which has a Cas9-containing CRISPR-Cas system. They discovered that in addition to the crRNA, a second small RNA exists, which they called trans-activating CRISPR RNA (tracrRNA) (Deltcheva et al., 2011). They showed that tracrRNA forms a duplex with crRNA, and that it is this duplex that guides Cas9 to its targets.

CRISPR systems can function heterologously in other species July, 2011 Virginijus Siksnys, Vilnius University, Lithuania

Siksnys and colleagues cloned the entire CRISPR-Cas locus from S. thermophilus (a Type II system) and expressed it in E. coli (which does not contain a Type II system), where they demonstrated that it was capable of providing plasmid resistance (Sapranauskas et al., 2011). This suggested that CRISPR systems are self-contained units and verified that all of the required components of the Type II system were known.

Biochemical characterization of Cas9-mediated cleavageSeptember, 2012 Virginijus Siksnys, Vilnius University, Lithuania

Taking advantage of their heterologous system, Siksnys and his team purified Cas9 in complex with crRNA from the E. coli strain engineered to carry the S. thermophilus CRISPR locus and undertook a series of biochemical experiments to mechanistically characterize Cas9s mode of action (Gasiunas et al., 2012).They verified the cleavage site and the requirement for the PAM, and using point mutations, they showed that the RuvC domain cleaves the non-complementary strand while the HNH domain cleaves the complementary site. They also noted that the crRNA could be trimmed down to a 20-nt stretch sufficient for efficient cleavage. Most impressively, they showed that they could reprogram Cas9 to target a site of their choosing by changing the sequence of the crRNA.

June, 2012 Charpentier and Jennifer Doudna, University of California, Berkeley

Similar findings as those in Gasiunas et al. were reported at almost the same time by Emmanuelle Charpentier in collaboration with Jennifer Doudna at the University of California, Berkeley (Jinek et al., 2012). Charpentier and Doudna also reported that the crRNA and the tracrRNA could be fused together to create a single, synthetic guide, further simplifying the system. (Although published in June 2012, this paper was submitted after Gasiunas et al.)

CRISPR-Cas9 harnessed for genome editingJanuary, 2013 Feng Zhang, Broad Institute of MIT and Harvard, McGovern Institute for Brain Research at MIT, Massachusetts

Zhang, who had previously worked on other genome editing systems such as TALENs, was first to successfully adapt CRISPR-Cas9 for genome editing in eukaryotic cells (Cong et al., 2013). Zhang and his team engineered two different Cas9 orthologs (from S. thermophilus and S. pyogenes) and demonstrated targeted genome cleavage in human and mouse cells. They also showed that the system (i) could be programmed to target multiple genomic loci, and (ii) could drive homology-directed repair. Researchers from George Churchs lab at Harvard University reported similar findings in the same issue of Science (Mali et al., 2013).


Barrangou, R., Fremaux, C., Deveau, H., Richards, M., Boyaval, P., Moineau, S., Romero, D.A., and Horvath, P. (2007). CRISPR provides acquired resistance against viruses in prokaryotes. Science 315, 17091712.

Bolotin, A., Quinquis, B., Sorokin, A.,and Ehrlich, S.D. (2005). Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology 151, 25512561.

Brouns, S.J., Jore, M.M., Lundgren, M., Westra, E.R., Slijkhuis, R.J., Snijders, A.P., Dickman, M.J., Makarova, K.S., Koonin, E.V., van der Oost, J. (2008) Small CRISPR RNAs guide antiviral defense in prokaryotes. Science 321, 960-964.

Cong, L., Ran, F.A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P.D., Wu, X., Jiang, W., Marraffini, L.A., et al. (2013). Multiplex genome engineering using CRISPR/Cas systems. Science 339, 819823.

Deltcheva, E., Chylinski, K., Sharma, C.M., Gonzales, K., Chao, Y., Pirzada, Z.A., Eckert, M.R., Vogel, J., and Charpentier, E. (2011). CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature 471, 602607.

Gasiunas, G., Barrangou, R., Horvath, P., and Siksnys, V. (2012). Cas9crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Pnas 109, E2579E2586.

Hale, C.R., Zhao, P., Olson, S., Duff, M.O., Graveley, B.R., Wells, L., Terns, R.M., and Terns, M.P. (2009). RNA-Guided RNA Cleavage by a CRISPR RNA-Cas Protein Complex. Cell 139, 945956.

Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J.A., and Charpentier, E. (2012). A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337, 816821.

Makarova, K.S., Grishin, N.V., Shabalina, S.A., Wolf, Y.I., Koonin, E.V. (2006). A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action. Biology Direct 2006, 1:7.

Mali, P., Yang, L., Esvelt, K.M., Aach, J., Guell, M., DiCarlo, J.E., Norville, J.E., and Church, G.M. (2013). RNA-guided human genome engineering via Cas9. Science 339, 823826.

Marraffini, L.A., and Sontheimer, E.J. (2008). CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA. Science 322, 18431845.

Mojica, F.J.M., D ez-Villase or, C.S., Garc a-Mart nez, J.S., and Soria, E. (2005). Intervening Sequences of Regularly Spaced Prokaryotic Repeats Derive from Foreign Genetic Elements. J Mol Evol 60, 174182.

Pourcel, C., Salvignol, G., and Vergnaud, G. (2005). CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies. Microbiology 151, 653663.

Sapranauskas, R., Gasiunas, G., Fremaux, C., Barrangou, R., Horvath, P., and Siksnys, V. (2011). The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli. Nucl. Acids Res. 39, gkr606gkr9282.

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CRISPR Timeline | Broad Institute

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Gene Therapy – Sickle Cell Anemia News

Gene therapy is an experimental technique that aims to treat genetic diseases by altering a disease-causing gene or introducing a healthy copy of a mutated gene to the body. The U.S. Food and Drug Administrationapprovedthe first gene therapy for an inherited disease a genetic form of blindness in December 2017.

Sickle cell anemia is caused by a mutation in the HBB gene which provides the instructions to make part of hemoglobin, the protein in red blood cells that carries oxygen.

Researchers are working on two different strategies to treat sickle cell anemia with gene therapy. Both of these strategies involve genetically altering the patients own hematopoietic stem cells. These are cells in the bone marrow that divide and specialize to produce different types of blood cells, including the red blood cells.

One strategy is to remove some of the patients hematopoietic stem cells, replace the mutated HBB gene in these cells with a healthy copy of the gene, and then transplant those cells back into the patient. The healthy copy of the gene is delivered to the cells using a modified, harmless virus. These genetically corrected cells will then hopefully repopulate the bone marrow and produce healthy, rather than sickled, red blood cells.

The other strategy is to genetically alter another gene in the patients hematopoietic stem cells so they boost production of fetal hemoglobin a form of hemoglobin produced by babies from about seven months before birth to about six months after birth. This type of hemoglobin represses sickling of cells in patients with sickle cell anemia, but most people only produce a tiny amount of it after infancy. Researchers aim to increase production of fetal hemoglobin in stem cells by using a highly specific enzyme to cut the cells DNA in the section containing one of the genes that suppress production of fetal hemoglobin. When the cell repairs its DNA, the gene no longer works and more fetal hemoglobin is produced.

Gene therapy offers an advantage over bone marrow transplant, in that complications associated with a bone marrow donation now the only cure for the disease such as finding the right match are not a concern.

Twelve clinical trials studying gene therapy to treat sickle cell anemia are now ongoing. Nine of the 12 are currently recruiting participants.

Four trials (NCT02186418, NCT03282656, NCT02247843, NCT02140554) are testing the efficacy and safety of gene therapy to replace the mutated HBB gene with a healthy HBB gene. These Phase 2 trials are recruiting both children and adults in the United States and Jamaica.

Three trials (NCT02193191, NCT02989701, NCT03226691) are investigating the use ofMozobil (plerixafor) in patients with sickle cell anemia to increase the production of stem cells to be used for gene therapy. This medication is already approved to treat certain types of cancer. All three are recruiting U.S. participants.

One trial (NCT00669305) is recruiting sickle cell anemia patients in Tennessee to donate bone marrow to be used in laboratory research to develop gene therapy techniques.

The final study(NCT00012545) is examining the best way to collect, process and store umbilical cord blood from babies with and without sickle cell anemia. Cord blood contains abundant stem cells that could be used in developing gene therapy for sickle cell anemia. This trial is open to pregnant women in Maryland both those who risk having an infant with sickle cell anemia, and those who do not.

One clinical trial (NCT02151526) conducted in France is still active but no longer recruiting participants. It is investigating the efficacy of gene therapy in seven patients. For the trial, a gene producing a therapeutic hemoglobin that functions similarly to fetal hemoglobin is introduced into the patients stem cells. A case studyfrom one of the seven was published in March 2017; it showed that the approach was safe and could be an effective treatment option for sickle cell anemia.


Sickle Cell Anemia News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

Original post:
Gene Therapy - Sickle Cell Anemia News

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Bone Marrow & Blood Stem Cell Transplant | IU Health

What are Bone Marrow and Stem Cells?

Bone marrow is a sponge-like tissue found inside bones. Within bone marrow, stem cells grow and develop into the three main types of blood cells:

Stem cells also grow many other cell types of the immune system.

At IU Health, we offer many types of bone marrow transplant, including:

For this type of transplant, we use your own stem cells. We collect the stem cells and then place them back into your body.

We use this method to treat blood-related cancers like multiple myeloma, non-Hodgkin lymphomas and Hodgkin disease, as well as certain germ-cell cancers.

CAR T-cell therapy is an emerging form of cancer immunotherapy. This therapy involves supercharging a patients T cells, a subtype of white blood cell, to recognize and attack cancer cells.

IU Health is the first healthcare system in Indiana to offer CAR T-cell therapy to treat non-Hodgkin lymphoma and Acute Lymphoblastic Leukemia (ALL).

For this type of transplant, the stem cells of another person are used. The donor can be a relative or a nonrelative whose blood cells are a close match.

The stem cells can come from peripheral (circulating) blood, bone marrow or umbilical cord blood (the blood in the cord connecting a fetus to a placenta).

This method is used to treat blood-related cancers like leukemias and some lymphomas or multiple myeloma. It is also used to treat bone marrow failure disorders like myelodysplastic syndrome (MDS) and aplastic anemia.

If you have an acute leukemia or lymphoma, IU Health Medical Center conducts haploidentical (half-matched) stem cell transplantation. This procedure also greatly expands the potential donor pool, making more patients eligible for the transplant.

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Bone Marrow & Blood Stem Cell Transplant | IU Health

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Learn How to Donate Bone Marrow | Be The Match

Join Be The Match Registry

The first step to being someone's cure is to join Be The Match Registry. If you are between the ages of 18-44, committed to donating to any patient in need, and meet the health guidelines, there are two ways to join.

Join in-person at a donor registry drive in your community.Be The One to Save a Life

Find a donor registry drive

Or join online today:

Join online

If you are between the ages of 18 and 44 patients especially need you. Research shows that cells from younger donors lead to more successful transplants. Doctors request donors in the 18-44 age group 86% of the time.

At donor registry drives, we focus on adding registry members most likely to donate. If you are between the ages of 45 and 60 and want to join the registry, you're welcome to join online with a $100 tax-deductible payment to cover the cost to join.

There are many other ways you can be the cure for patients with blood cancers.

Check outFAQs about donationor call us at 1 (800) MARROW2 for more information about bone marrow donation.

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Learn How to Donate Bone Marrow | Be The Match

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Selecting Male Genetics for Cannabis Plants – School of … Exclusive Videos- Seeds- Get 10% off use coupon code- SOHN10Visit our store-

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Nine Things To Know About Stem Cell Treatments A Closer …

It can be hard to tell the difference between doctors conducting responsible clinical trials and clinics selling unproven treatments. One common differentiator is the way a treatment is marketed. Most specialized doctors receive patient referrals, while clinics selling stem cell treatments tend to market directly to patients, often through persuasive language on the Internet, Facebook and in newspaper advertisements.

Clinics peddling unproven stem cell treatments frequently overstate the benefits of their offerings and use patient testimonials to support their claims. These testimonials can be intentionally or unintentionally misleading. For example, a person may feel better immediately after receiving a treatment, but the perceived or actual improvement may be due to other factors, such as an intense belief that the treatment will work, auxiliary treatments accompanying the main treatment, healthy lifestyle changes adapted in conjunction with the treatment and natural fluctuations in the disease or condition. These factors are complex and difficult to measure objectively outside the boundaries of carefully designed clinical trials. Learn more about why we need to perform clinical trials here.

Beware of clinics that use persuasive language, including patient testimonials, on the Internet, Facebook and newspapers, to market their treatments, instead of science-based evidence.

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Nine Things To Know About Stem Cell Treatments A Closer ...

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