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Researchers discover genetic origins of myelodysplastic syndrome using stem cells

By Stem Cell Medical Center

(New York - March 25, 2015) Induced pluripotent stem cells (iPSCs) -- adult cells reprogrammed back to an embryonic stem cell-like state--may better model the genetic contributions to each patient's particular disease. In a process called cellular reprogramming, researchers at Icahn School of Medicine at Mount Sinai have taken mature blood cells from patients with myelodysplastic syndrome (MDS) and reprogrammed them back into iPSCs to study the genetic origins of this rare blood cancer. The results appear in an upcoming issue of Nature Biotechnology.

In MDS, genetic mutations in the bone marrow stem cell cause the number and quality of blood-forming cells to decline irreversibly, further impairing blood production. Patients with MDS can develop severe anemia and in some cases leukemia also known as AML. But which genetic mutations are the critical ones causing this disease?

In this study, researchers took cells from patients with blood cancer MDS and turned them into stem cells to study the deletions of human chromosome 7 often associated with this disease.

"With this approach, we were able to pinpoint a region on chromosome 7 that is critical and were able to identify candidate genes residing there that may cause this disease," said lead researcher Eirini Papapetrou, MD, PhD, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai.

Chromosomal deletions are difficult to study with existing tools because they contain a large number of genes, making it hard to pinpoint the critical ones causing cancer. Chromosome 7 deletion is a characteristic cellular abnormality in MDS and is well-recognized for decades as a marker of unfavorable prognosis. However, the role of this deletion in the development of the disease remained unclear going into this study.

Understanding the role of specific chromosomal deletions in cancers requires determining if a deletion has observable consequences as well as identifying which specific genetic elements are critically lost. Researchers used cellular reprogramming and genome engineering to dissect the loss of chromosome 7. The methods used in this study for engineering deletions can enable studies of the consequences of alterations in genes in human cells.

"Genetic engineering of human stem cells has not been used for disease-associated genomic deletions," said Dr. Papapetrou. "This work sheds new light on how blood cancer develops and also provides a new approach that can be used to study chromosomal deletions associated with a variety of human cancers, neurological and developmental diseases."

Reprogramming MDS cells could provide a powerful tool to dissect the architecture and evolution of this disease and to link the genetic make-up of MDS cells to characteristics and traits of these cells. Further dissecting the MDS stem cells at the molecular level could provide insights into the origins and development of MDS and other blood cancers. Moreover, this work could provide a platform to test and discover new treatments for these diseases.

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This study was supported by grants from the National Institutes of Health, the American Society of Hematology, the Sidney Kimmel Foundation for Cancer Research, the Aplastic Anemia & MDS International Foundation, the Ellison Medical Foundation, the Damon Runyon Cancer Research Foundation, the University of Washington Royalty Research Fund, and a John H. Tietze Stem Cell Scientist Award.

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Researchers discover genetic origins of myelodysplastic syndrome using stem cells

Growing 3D miniature lungs from stem cells

By Stem Cell Medical Center

Chuck Bednar for redOrbit.com @BednarChuck

Researchers from the University of Michigan have cooked-up the perfect recipe for growing miniature, three-dimensional human lungs from stem cells, but you wont find this recipe in a cookbook it appears in the latest edition of the journal eLife.

Lead author Dr. Jason Spence, a professor at the UM Medical School in Ann Arbor, and colleagues from the Cincinnati Childrens Hospital Medical Center, the University of California, San Francisco (UCSF), Seattle Childrens Hospital and the University of Washington reported in their paper how they converted human pluripotent stem cells (hPSCs) into mini lungs.

Their work compliments with other recent research in the field (including building lung tissue from the scaffold of donated organs), the publishers of eLife said, and their method produces an organ that is more similar to the human lung than previous efforts because it can grow structures that closely resemble both the large proximal airways and the small distal airways.

The process

They took hPSCs (both embryonic and induced) and added a protein known as ActivinA, which is involved in lung development. They left the stem cells for four days, and during this period, a type of tissue known as endoderm formed. Found in early embryos, forms several internal organ types, including the lung and the liver.

[STORY: Testing astronauts' lungs in the ISS airlock]

Next, they added a second protein a growth factor called Noggin and again left the growing tissues for four days. The endoderm was then induced to form 3D spherical structures known as the foregut spheroids. At this point, the scientists worked to make these structures expand and form into lung tissue by exposing the cells to proteins involved in lung development.

Once the spheroids were transferred into the protein mixture, they were allowed to incubate at room temperature for 10 minutes until the mixture solidified. They were treated with additional proteins every four days and transferred into a new protein mixture every 10 to 15 days.

The process is used to create lung organoids that should survive in culture for over 100 days and develop into well-organized structures containing cell types found in the lung, the study authors explained. The mini-lungs are essentially self-organizing, and once they are formed, they require no additional manipulation to generate three-dimensional tissues, they added.

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Growing 3D miniature lungs from stem cells

Celprogen Released Stem Cell Active Ingredients for the Cosmetic Industry Tested and Validated in Cosmetic Products …

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Celprogen Released Stem Cell Active Ingredients for the Cosmetic Industry Tested and Validated in Cosmetic Products for a Decade

The present invention relates to culturing stem cells in animal free conditions has been developed and optimized by Celprogen utilizing single use bioreactor technology. The cosmetic industry has benefited from this technology for their regenerative skin care product lines. The topical application of these skin care products utilizing Celprogens Stem Cell Derived Conditioned Media have been in the market for 10 plus years.

About Celprogen Inc. Celprogen Inc. is a global Stem Cell Research & Therapeutics company which is developing a proprietary portfolio of unique therapeutics products and life science research tools that includes genetic engineering technologies, stem cell technologies for regenerative medicine, as well as bio-engineering products for tissue & organ transplants. Headquartered in Torrance, California, Celprogen is committed to the research, development, and manufacture of quality Stem Cell, Cancer Stem Cell and Primary Cell Culture products to serve our global community. Additional information about Celprogen is available at http://www.celprogen.com.

For additional information on the product line contact: Jay Sharma Phone: 310 542 8822 info@celprogen.com http://www.celprogen.com

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Celprogen Released Stem Cell Active Ingredients for the Cosmetic Industry Tested and Validated in Cosmetic Products ...

Canadians honoured for medical research

By Stem Cell Medicine

By Helen Branswell, The Canadian Press

TORONTO - One of the co-discoverers of the Ebola virus and a leading Canadian stem cell researcher are among this year's winners of the prestigious Canada Gairdner Awards.

Dr. Peter Piot is the recipient of the Canada Gairdner Global Health Award, recognizing his work on the discovery of the Ebola virus in 1976 and his leadership in the global response to the HIV-AIDS epidemic.

Dr. Janet Rossant, chief of research at Toronto's Hospital for Sick Children, is the recipient of the 2015 Canada Gairdner Wightman Award, which honours a Canadian who has demonstrated outstanding leadership in medicine and medical science.

Five international scientists are also being honoured with Canada Gairdner Awards, two each from the United States and Japan and one from Switzerland.

The Gairdners are among the world's most esteemed medical research prizes and each carries a prize of $100,000.

They are awarded annually by the Gairdner Foundation; 82 Gairdner winners have gone on to receive Nobel Prizes.

"The Canada Gairdner Awards distinguish Canada as a leader in biomedical research, raising the profile of science both nationally and on the world stage," Dr. John Dirks, the foundation's president and scientific director, said in a statement announcing the 2015 honourees.

"This year's winners are an exceptional example of the wide implications basic cellular discovery can have on future translational discoveries."

The international winners are:

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Canadians honoured for medical research

SickKids Chief of Research and University of Toronto Professor, Dr. Janet Rossant, named recipient of 2015 Canada …

By Stem Cell Medicine

TORONTO The Hospital for Sick Children (SickKids) and the University of Toronto (U of T) are thrilled to congratulate Dr. Janet Rossant on being named the recipient of the 2015 CanadaGairdnerWightman Award, in recognition of her extensive scientific contributions to developmental biology, her international leadership in stem cell biology and policy-making, and for her pivotal role in advancing research programs for childrens health. The announcement was made in Toronto on March 25, 2015.

It is a huge honour to receive this award on behalf of SickKids, U of T and all the people throughout my career who have helped make my journey in science such fun, says Rossant, Chief of Research and Senior Scientist in the Developmental & Stem Cell Biology Program at SickKids, and University Professor in the Departments of Molecular Genetics, Obstetrics and Gynaecology at U of T.

The CanadaGairdnerWightman Award is given to a scientist who has demonstrated outstanding national leadership in medicine and medical science in Canada.

Rossant is an internationally recognized scientist whose 40-year career has been devoted to advancing the fundamental understanding of embryo development and stem cell origins. In addition to her role as Chief of Research at SickKids, Rossant has revolutionized the landscape surrounding stem cell research through an array of key leadership roles, including President of the International Society for Stem Cell Research, Deputy Scientific Director of the Canadian Stem Cell Network, and Director of the Ontario Institute for Regenerative Medicine.

As a leader in stem cell research, Rossant has contributed significantly to the scientific communitys understanding of stem cells, which have the potential to unlock new therapies for a wide variety of disorders from cancer to diabetes and neurodegenerative diseases. Rossants research into personalized stem cell medicine is primed to make significant improvements to global health care and quality of life. She is a respected voice in the stem cell debate and has established Canada as a global forerunner in stem cell and genetic research.

Rossant pioneered new techniques to manipulate the mouse genome, enabling the mouse to become the preeminent model for understanding the function of the human genome sequence. This has been a key resource to those studying the molecular basis of many human diseases and the effectiveness of various drugs for treatments.

Under Dr. Rossants visionary leadership, SickKids national and international prominence as one of the worlds most celebrated child health research centres has continued to grow and flourish, says Dr. Michael Apkon, SickKids President and CEO. The entire SickKids community joins me in congratulating Dr. Rossant for this well-deserved recognition and prestigious award.

Rossants vision for increased multidisciplinary collaboration as a critical tool to propel scientific discovery guided the design and governance of SickKids state-of-the-art research tower The Peter Gilgan Centre for Research and Learning. The Gilgan Centre creates an environment for scientists, clinicians, and research staff from diverse disciplines to work together in addressing critical child health issues.

A highly prolific Canadian scientist, Rossant has over 379 publications to her name including over 58,000 lifetime citations. In her long-standing career in Canada, she has trained 56 post-doctoral fellows and 27 graduate students.

Professor Rossant is doing brilliant, exciting work on the cutting edge of global biomedical research work that holds great promise for the advancement of our knowledge of human biology and disease, says Meric Gertler, President of the University of Toronto. I am delighted that her world-leading excellence has been recognized by the Gairdner Foundation. On behalf of the entire U of T community, I extend hearty congratulations.

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SickKids Chief of Research and University of Toronto Professor, Dr. Janet Rossant, named recipient of 2015 Canada ...

Cleveland Clinic Researchers First to Demonstrate Significant Blocking of Opioid Tolerance With Mesenchymal Stem Cell …

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Newswise March 24, 2015, NATIONAL HARBOR, Md. - Mesenchymal stem cell (MSC) transplantation reduced opioid tolerance and opioid-induced hyperalgesia caused by daily morphine injections in rats, according to new research. The results could herald stem cell transplantation as an innovative, safe, efficacious and cost-effective therapy to treat pain and opioid tolerance, said researchers, who presented results in a Plenary Research Highlight session at the 31st Annual Meeting of the American Academy of Pain Medicine.

Not only was opioid tolerance prevented when the rats were transplanted with MSC before repeated morphine injections, but tolerance was reversed when the rats were treated after opioid tolerance had developed, results demonstrated.

MSCs have a remarkable anti-inflammatory effect and a powerful anti-tolerance effect, said the studys principal investigator, Jianguo Cheng, M.D., Ph.D., who led the research team from the Cleveland Clinic, in Ohio. Although clinical trials are still three to five years away, he said, eventually, The results may apply to millions of patients with a wide range of pain states, including cancer pain and other intractable chronic pain that requires long-term opioid therapy.

Furthermore, Cheng characterized the procedure as practical, in light of readily available sources of stem cells, reliable stem cell technology, the simplicity of transplantation procedures and the fact that clinical trials are already underway involving autoimmune and other diseases.

The Institute of Medicine report on pain in America documented millions who suffer with chronic pain (Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. National Academies Press [US]; 2011). Opioid therapy is a cornerstone component of pain management for many people with severe, ongoing pain; however, side effects such as tolerance and the risks posed by abuse, addiction and drug overdose limit its utility. Tolerance, a physiologic process in which the patients body adjusts to a dose and no longer achieves pain relief, is a common limitation with opioid therapy. The higher doses that result can limit effectiveness and compromise safety.

Glial cells are of growing interest in pain research and have been implicated in the development of tolerance. Glial cell activity also produces pain through the release of products that excite the nervous system, playing an important role in the spinal cord during nerve injury. Furthermore, the opioids used to treat pain, also can induce glial activity, causing pain relief to drop and unwanted opioid effects, including tolerance, dependence, reward and decreased breathing, to grow. A focus of research, then, is to separate the desired effect of pain relief from the unwanted opioid effects (Watkins et al, Trends in Pharmacological Sciences 2009;30(11): 581-91).

Interest in transplant of stem cells is another maturing research avenue (Hsu et al, Cell Transplant 2007;16(2):133-50). MSCs can differentiate into a variety of cell types and have been investigated for potential repair of damaged neural cells and for calming inflammation in the immune system to promote recovery after traumatic brain injury (Zhang et al, J Neuroinflammation 2013;10(1):106).

Following this line of research, the study investigators wondered whether they could create an anti-tolerance therapy by transplanting MSCs into the intrathecal space surrounding the spinal cord. With approval by the Cleveland Clinic Institutional Animal Care and Use Committee and funding through the Department of Defenses Congressionally Directed Medical Research Programs, they compared the withdrawal thresholds of the hind paws in response to painful mechanical and thermal stimuli in two groups of rats that received daily morphine injections. The first group was treated with MSC transplantation and the control group with phosphate-buffered saline (PBS).

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Scientists coax stem cells to form 3-D mini lungs

By Stem Cell Medical Center

Human lung organoids will help scientists learn more about lung diseases, test new drugs

IMAGE:Scientists, led by the University of Michigan Medical School, coax stem cells to form mini lungs, 3-D structures that mimic human lungs and survived in the lab for 100 days.... view more

Credit: University of Michigan Health System

ANN ARBOR, Mich. - Scientists have coaxed stem cells to grow the first three-dimensional mini lungs.

Previous research has focused on deriving lung tissue from flat cell systems or growing cells onto scaffolds made from donated organs.

In a study published in the online journal eLife the multi-institution team defined the system for generating the self-organizing human lung organoids, 3D structures that mimic the structure and complexity of human lungs.

"These mini lungs can mimic the responses of real tissues and will be a good model to study how organs form, change with disease, and how they might respond to new drugs," says senior study author Jason R. Spence, Ph.D., assistant professor of internal medicine and cell and developmental biology at the University of Michigan Medical School.

The scientists succeeded in growing structures resembling both the large airways known as bronchi and small lung sacs called alveoli.

Since the mini lung structures were developed in a dish, they lack several components of the human lung, including blood vessels, which are a critical component of gas exchange during breathing.

Still, the organoids may serve as a discovery tool for researchers as they churn basic science ideas into clinical innovations. A practical solution lies in using the 3-D structures as a next step from, or complement to, animal research.

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Scientists coax stem cells to form 3-D mini lungs

Scientists Coax Stem Cells to Form 3D Mini Lungs

By Stem Cell Medical Center

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Newswise ANN ARBOR, Mich. Scientists have coaxed stem cells to grow the first three-dimensional mini lungs.

Previous research has focused on deriving lung tissue from flat cell systems or growing cells onto scaffolds made from donated organs. In a study published in the online journal eLife the multi-institution team defined the system for generating the self-organizing human lung organoids, 3D structures that mimic the structure and complexity of human lungs.

These mini lungs can mimic the responses of real tissues and will be a good model to study how organs form, change with disease, and how they might respond to new drugs, says senior study author Jason R. Spence, Ph.D., assistant professor of internal medicine and cell and developmental biology at the University of Michigan Medical School.

The scientists succeeded in growing structures resembling both the large airways known as bronchi and small lung sacs called alveoli.

Since the mini lung structures were developed in a dish, they lack several components of the human lung, including blood vessels, which are a critical component of gas exchange during breathing.

Still, the organoids may serve as a discovery tool for researchers as they churn basic science ideas into clinical innovations. A practical solution lies in using the 3-D structures as a next step from, or complement to, animal research.

Cell behavior has traditionally been studied in the lab in 2-D situations where cells are grown in thin layers on cell-culture dishes. But most cells in the body exist in a three-dimensional environment as part of complex tissues and organs.

Researchers have been attempting to re-create these environments in the lab, successfully generating organoids that serve as models of the stomach, brain, liver and human intestine.

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Scientists Coax Stem Cells to Form 3D Mini Lungs

TSRI Team Discovers Enzyme that Keeps Blood Stem Cells Functional to Prevent Anemia

By Stem Cell Clinic

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Newswise LA JOLLA, CA March 23, 2015 Stem cells can generate any type of cell in the body, but they are inactive most of the timeand for good reason. When stem cells become too active and divide too often, they risk acquiring cell damage and mutations. In the case of blood stem cells (also called hematopoietic stem cells or HSCs), this can lead to blood cancers, a loss of blood cells and an impaired ability to fight disease.

Now scientists at The Scripps Research Institute (TSRI) have found that a particular enzyme in HSCs is key to maintaining healthy periods of inactivity. Their findings, published recently in the journal Blood, show that animal models without this enzyme experience dangerous HSC activation and ultimately succumb to lethal anemia.

These HSCs remain active too long and then disappear, said TSRI Associate Professor Karsten Sauer, senior author of the new study. "As a consequence, the mice lose their red blood cells and die."

With this new understanding of the enzyme, called Inositol trisphosphate 3-kinase B (ItpkB), scientists are closer to improving therapies for diseases such as bone marrow failure syndrome, anemia, leukemia, lymphoma and immunodeficiencies.

Stem Cells Need Rest

HSCs are a type of adult stem cell that live in little niches in the bone marrow. They are normally inactive, or quiescent, and only divide to self-renew about every two months.

However, when mature blood cells are lost, for example through severe bleeding or during infections, HSCs become activated to generate new progenitor cellsthe cells that replenish the blood supply and produce immune cells to fight disease. Once the blood cells have been replenished, the HSCs become quiescent again.

The balance between inactivity and activity is important because HSC activation generates side products that harm HSCs. In addition, every division introduces a risk of mutation, sometimes leading to cancer. Its like a car wearing down its own engine while it is doing its work, said Sauer. "Like people, HSCs need long periods of rest to remain healthy and work well."

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TSRI Team Discovers Enzyme that Keeps Blood Stem Cells Functional to Prevent Anemia

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