Stem Cell Clinic

Soft substrates may promote the production of induced pluripotent stem cells

By Stem Cell Treatment

17 hours ago Figure 1: Fluorescence microscopy image of cells cultured on soft (left) and rigid (right) substrates. Actin filaments (red) in these cells display dramatic differences in number and organization depending on substrate elasticity. Credit: The Society for Biotechnology, Japan

Converting adult cells into stem cells that can develop into other types of specialized cells is one of the most active areas of medical research, holding great promise for the treatment of disease and repair of damaged tissues. The techniques available for reprogramming adult cells into stem cells, however, remain imperfect and inefficient. In research that could help improve reprogramming efficiency, Sayaka Higuchi and colleagues from the RIKEN Quantitative Biology Center have now found that culturing cells on soft or elastic substrates enhances expression of some of the markers of stem cell reprogramming.

Motivated by previous observations that culturing cells on soft surfaces can affect their ability to multiply and renew, Higuchi and her team set out to examine whether the same principle might be applicable to enhancing the efficiency of producing induced pluripotent stem (iPS) cellsa type of stem cell that is reprogrammed from mature adult fibroblast cells using methods such as the introduction of genetic factors.

The researchers investigated the effect of culturing mouse and human fibroblasts treated with these factors on a range of gel substrates with different compositions and elasticities. They found that genes associated with reprogramming into stem cells were more active in the cells cultured on some of the soft surfaces than in the cells cultured on conventional rigid plastic dishes. They also found that changes in substrate elasticity significantly altered the amount and distribution of actin fibers, suggesting that the actin protein may be involved in mediating the effect of the substrate on the reprogramming process (Fig. 1).

Although the team did not proceed to the actual generation of viable stem cells, the results provide some promising avenues for further research. "It is likely that soft substrates promote only the initiation of the reprogramming process," explains Higuchi. "Even so, the results could lead to more effective and reproducible ways to produce pluripotent stem cells."

Another possibility of particular interest to Higuchi follows from her team's observations that the combination of chemical treatment with substrate manipulation could potentially form the basis for a full reprogramming method that does not involve gene transfera process that involves retroviral infection of mature cells with pluripotency factors. "Gene transfer is still the main method for full reprogramming of iPS cells," says Higuchi, "but if we can find a method for producing pluripotent stem cells that avoids this process, the cells may be much safer for medical use."

Explore further: A protein required for integrity of induced pluripotent stem cells

More information: Higuchi, S., Watanabe, T. M., Kawauchi, K., Ichimura, T. & Fujita, H. "Culturing of mouse and human cells on soft substrates promote the expression of stem cell markers." Journal of Bioscience and Bioengineering 6, 749755 (2014). DOI: 10.1016/j.jbiosc.2013.11.011

Cell reprogramming converts specialised cells such as nerve cells or skin cells towards an embryonic stem cell state. This reversal in the evolutionary development of cells also requires a reversal in the ...

A research team led by the group of Professor Yasuhiro Yamada, Center for iPS Cell Research and Application (CiRA), Kyoto University, has discovered that when cells are subjected to incomplete reprogramming ...

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Soft substrates may promote the production of induced pluripotent stem cells

Protein Discovery Could Boost Efficacy Of Bone Marrow Replacement Treatments

By Stem Cell Medicine

May 1, 2014

Image Caption: The continuous, necessary production of blood cells, including these red blood cells captured in a scanning micrograph by Thomas Deerinck, is the responsibility of hematopoietic stem cells found in bone marrow. Credit: Thomas Deerinck, UC San Diego

University of California San Diego

Researchers at the University of California, San Diego School of Medicine report that a protein called beta-catenin plays a critical, and previously unappreciated, role in promoting recovery of stricken hematopoietic stem cells after radiation exposure.

The findings, published in the May 1 issue of Genes and Development, provide a new understanding of how radiation impacts cellular and molecular processes, but perhaps more importantly, they suggest new possibilities for improving hematopoietic stem cell regeneration in the bone marrow following cancer radiation treatment.

Ionizing radiation exposure accidental or deliberate can be fatal due to widespread destruction of hematopoietic stem cells, the cells in the bone marrow that give rise to all blood cells. A number of cancer treatments involve irradiating malignancies, essentially destroying all exposed blood cells, followed by transplantation of replacement stem cells to rebuild blood stores. The effectiveness of these treatments depends upon how well the replacement hematopoietic stem cells do their job.

In their new paper, principal investigator Tannishtha Reya, PhD, professor in the department of pharmacology, and colleagues used mouse models to show that radiation exposure triggers activation of a fundamental cellular signaling pathway called Wnt in hematopoietic stem and progenitor cells.

The Wnt pathway and its key mediator, beta catenin, are critical for embryonic development and establishment of the body plan, said Reya. In addition, the Wnt pathway is activated in stem cells from many tissues and is needed for their continued maintenance.

The researchers found that mice deficient in beta-catenin lacked the ability to activate canonical Wnt signaling and suffered from impaired hematopoietic stem cell regeneration and bone marrow recovery after radiation. Specifically, mouse hematopoietic stem cells without beta-catenin could not suppress the production of oxidative stress molecules that damage cell structures. As a result, they could not recover effectively after radiation or chemotherapy.

Our work shows that Wnt signaling is important in the mammalian hematopoietic system, and is critical for recovery from chemotherapy and radiation, Reya said. While these therapies can be life-saving, they take a heavy toll on the hematopoietic system from which the patient may not always recover.

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Protein Discovery Could Boost Efficacy Of Bone Marrow Replacement Treatments

Stem cells from some infertile men form germ cells when transplanted into mice, study finds

By Stem Cell Medical Center

PUBLIC RELEASE DATE:

1-May-2014

Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center

STANFORD, Calif. Stem cells made from the skin of adult, infertile men yield primordial germ cells cells that normally become sperm when transplanted into the reproductive system of mice, according to researchers at the Stanford University School of Medicine and Montana State University.

The infertile men in the study each had a type of genetic mutation that prevented them from making mature sperm a condition called azoospermia. The research suggests that the men with azoospermia may have had germ cells at some point in their early lives, but lost them as they matured to adulthood.

Although the researchers were able to create primordial germ cells from the infertile men, their stem cells made far fewer of these sperm progenitors than did stem cells from men without the mutations. The research provides a useful, much-needed model to study the earliest steps of human reproduction.

"We saw better germ-cell differentiation in this transplantation model than we've ever seen," said Renee Reijo Pera, PhD, former director of Stanford's Center for Human Embryonic Stem Cell Research and Education. "We were amazed by the efficiency. Our dream is to use this model to make a genetic map of human germ-cell differentiation, including some of the very earliest stages."

Unlike many other cellular and physiological processes, human reproduction varies in significant ways from that of common laboratory animals like mice or fruit flies. Furthermore, many key steps, like the development and migration of primordial germ cells to the gonads, happen within days or weeks of conception. These challenges have made the process difficult to study.

Reijo Pera, who is now a professor of cell biology and neurosciences at Montana State University, is the senior author of a paper describing the research, which will be published May 1 in Cell Reports. The experiments in the study were conducted at Stanford, and Stanford postdoctoral scholar Cyril Ramathal, PhD, is the lead author of the paper.

The research used skin samples from five men to create what are known as induced pluripotent stem cells, which closely resemble embryonic stem cells in their ability to become nearly any tissue in the body. Three of the men carried a type of mutation on their Y chromosome known to prevent the production of sperm; the other two were fertile.

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Stem cells from some infertile men form germ cells when transplanted into mice, study finds

Legislature could boost U stem cell research

By Stem Cell Clinic

The future of the University of Minnesotas regenerative medicine research program is looking brighter than ever.

State and federal leaders in the past have denied funding for the Universitys Office of Regenerative Medicine, which includes the Stem Cell Institute, because some had ethical disagreements with stem cell research.

But this legislative session, with a DFL majority and an overall shift in public opinion, researchers and legislators are confident funding will come through this year.

The current House bill sets aside $450,000 for the Office of Regenerative Medicine, while the Senate version outlines a $5 million increase each year from 2015-17. The bills texts dont specify how funds should be used and how they would be divided between the University and the Mayo Clinic, its research partner.

The Senates bill mandates that anadvisory task force comprised of members from the University, the Mayo Clinic and private industry, as well as two other regenerative medicine experts, recommend how to spend the state funding.

Dayton didnt include funds for the research in his original budget proposal this year, but Sen. Terri Bonoff, DFL-Minnetonka, said there seems to be a general consensus among legislators to work together and decide on a funding amount.

I have not heard many naysayers, she said.

Changing perceptions

The state plays a major role in moving the institutes research forward.

These days, legislators are more open to it than they were in the past, said Dr. Andre Terzic, director of the Mayo Clinic Center for Regenerative Medicine.

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Legislature could boost U stem cell research

Sperm precursors made from stem cells of infertile men

By Uncategorized

PUBLIC RELEASE DATE:

1-May-2014

Contact: Mary Beth O'Leary moleary@cell.com 617-397-2802 Cell Press

Researchers reporting in the Cell Press journal Cell Reports on May 1st have successfully coaxed stem cells made from the skin cells of infertile men into producing sperm cell precursors. These induced pluripotent stem cells (iPSCs) produced sperm precursors following transplantation into the testes of mice.

The findings help to explain a genetic cause of male infertility and offer a window into basic sperm biology. The approach also holds considerable potential for clinical application, the researchers say.

"Our results are the first to offer an experimental model to study sperm development," said Renee Reijo Pera of the Institute for Stem Cell Biology & Regenerative Medicine and Montana State University. "Therefore, there is potential for applications to cell-based therapies in the clinic, for example, for the generation of higher quality and numbers of sperm in a dish.

"It might even be possible to transplant stem-cell-derived germ cells directly into the testes of men with problems producing sperm," she added. However, getting to that point will require considerable study to ensure the safety and practicality.

Infertility affects 10% to 15% of couples. Moreover, as the researchers note, genetic causes of infertility are surprisingly prevalent among men, most commonly due to the spontaneous loss of key genes on the Y sex chromosome. But the causes at the molecular level have not been well understood.

Reijo Pera said her primary motivation is to understand the fundamental decision early in development that enables the production of sperm cell precursors and ultimately sperm. One way to do that is to study cells lacking genes that are required for sperm production.

The researchers looked to infertile but otherwise normal men with deletions encompassing three Y chromosome azoospermia factor (AZF) regions, which are associated with the production of few or no sperm. They found that iPSCs derived from AZF-deleted cells were compromised in their ability to form sperm in a dish. But when those cells were transplanted into the seminiferous tubules of mice, they produced germ-cell-like cells (though significantly fewer than iPSCs derived from people without the AZF deletion do).

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Sperm precursors made from stem cells of infertile men

Regenexx Stem Cell Procedures – New York and New Jersey …

By Stem Cell Treatment

In October 2011, the Rehabilitation Medicine Center became the first east-coast clinic licensed and trained to perform the Regenexx Family of Regenerative Medicine Procedures.

These advanced stem cell and blood platelet procedures provide non-surgical treatment options for those suffering from joint or bone pain, torn or strained tendons and ligaments, or other common injuries and degenerative conditions. Regenexx procedures offer a viable alternative for patients with chronic pain and who may be considering surgery.

Stem Cells are in all of us and they are responsible for healing injured bone, ligaments, tendons and tissues. As we get older or injured, we sometimes cannot get enough of these cells into the area in need. The Regenexx Procedures help solve that problem by precisely delivering a high concentration of stem cells into the injured area and aiding your bodys ability to heal naturally. Patients experience very little down time and they typically avoid the long, painful rehabilitation periods that often follow surgery to restore joint strength and mobility.Procedures are performed in our New Jersey office, but evaluations can take place in our New York City or New Jersey clinics.To determine if youre a candidate for these procedures, please complete our Candidate Form.

Regenexx Procedures were recently featured on The Doctors TV show. The episode featured Dr. Christopher J. Centeno and Dr. Ron Hanson from the Centeno-Schultz Clinic in Colorado, along with patient Barbee James, who sought stem cell treatment following traditional knee surgery. The 6 minute video provides a nice overview of the Regenexx-SD (Same Day) Stem Cell procedure, which is now offered at the Rehabilitation Medicine Center.

On February 28, 2013 Seattle King TV featured Regenexx patient Paul Lyon, who underwent a Regenexx-SD knee procedure. The story looks at his results and includes an interview with Dr. Christopher Centeno, founder of the Regenexx Procedures.

If you are suffering from a joint injury, joint pain, a non-healing fracture or a degenerative condition like osteoarthritis, you may be a good candidate for these ground-breaking stem cell and blood platelet treatments. Please complete the Procedure Candidate Form below and we will immediately email you more information.

Download the Free E-Book on Regenerative Orthopedics Orthopedics 2.0 How Regenerative Medicine will Create the Next Generation of Less Invasive Orthopedics. Authored by the Centeno-Schultz clinics Dr. Chris Centeno, this book explains the comprehensive Orthopedics 2.0 approach to patients.

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Regenexx Stem Cell Procedures - New York and New Jersey ...

Stem cell jab is 'five times better than drugs' for treating people with life-threatening heart conditions

By Stem Cell Treatment

British study involved more than 1,000 sufferers of chronic heart disease Indicated injecting stem cells into heart significantly increase survival rates Those who had the treatment less likely to be readmitted to hospital Patients who had injection also more likely to have improved heart function

By Daily Mail Reporter

Published: 18:37 EST, 29 April 2014 | Updated: 02:30 EST, 30 April 2014

Stem cells could be five times more effective in treating people with life-threatening heart diseases than conventional drugs.

A study involving more than 1,000 sufferers of chronic heart disease indicated that injecting stem cells into the heart can significantly increase survival rates after a year.

It found that those who underwent the treatment were less likely to be readmitted to hospital and also had improved heart function.

Stem cells could be five times more effective in treating people with life-threatening heart diseases than conventional drugs

Stem cell treatment for heart disease is currently limited to specialist research centres, where cells are extracted from a patients own blood or bone marrow and used to repair damaged tissue in the heart and arteries.

The Cochrane Heart Review Group looked at data involving 1,255 people from 23 trials, where all patients received treatments currently available to the public.

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Stem cell jab is 'five times better than drugs' for treating people with life-threatening heart conditions

Stem cell treatment repairs damaged heart tissue in monkeys

By Stem Cell Treatment

Sony increases net loss forecast to 130 billion yen

The Nation - Thursday 1st May, 2014

Tokyo - Sony Corp Thursday increased its predicted net loss to 130 billion yen (1.27 billion dollars) for the last financial year due to additional costs on its personal computer business and disc ...

The Nation - Thursday 1st May, 2014

Jakarta (dpa) - A five-year-old Indonesian boy jumped to his death in Jakarta after his mother forbade him viewing the movie Spiderman, local media reported ...

The Nation - Thursday 1st May, 2014

CHENNAI, India (AFP) - Twin bombs planted on a train killed one person and wounded 14 others in the southern Indian port of Chennai Thursday, the latest attack during ongoing national elections, ...

West Australian - Thursday 1st May, 2014

Bangkok (AFP) - A Thai comedian and prominent "Red Shirt" political activist lost an appeal Thursday against a two-year prison term under the kingdom's strict royal defamation law. ...

Rigzone - Thursday 1st May, 2014

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Stem cell treatment repairs damaged heart tissue in monkeys

Stem Cells Taken From Teeth Can Make Brain-like Cells

By Stem Cell Treatment

May 1, 2014

Image Caption: This is the distinct neuronal-like appearance of a mouse-derived dental pulp stem cell following the induction process. Credit: Dr. Kylie Ellis, University of Adelaide.

University of Adelaide

University of Adelaide researchers have discovered that stem cells taken from teeth can grow to resemble brain cells, suggesting they could one day be used in the brain as a therapy for stroke.

In the Universitys Centre for Stem Cell Research, laboratory studies have shown that stem cells from teeth can develop and form complex networks of brain-like cells. Although these cells havent developed into fully fledged neurons, researchers believe its just a matter of time and the right conditions for it to happen.

Stem cells from teeth have great potential to grow into new brain or nerve cells, and this could potentially assist with treatments of brain disorders, such as stroke, says Dr Kylie Ellis, Commercial Development Manager with the Universitys commercial arm, Adelaide Research & Innovation (ARI).

Dr Ellis conducted this research as part of her Physiology PhD studies at the University, before making the step into commercialization. The results of her work have been published in the journal Stem Cell Research & Therapy.

The reality is, treatment options available to the thousands of stroke patients every year are limited, Dr Ellis says. The primary drug treatment available must be administered within hours of a stroke and many people dont have access within that timeframe, because they often cant seek help for some time after the attack.

Ultimately, we want to be able to use a patients own stem cells for tailor-made brain therapy that doesnt have the host rejection issues commonly associated with cell-based therapies. Another advantage is that dental pulp stem cell therapy may provide a treatment option available months or even years after the stroke has occurred, she says.

Dr Ellis and her colleagues, Professors Simon Koblar, David OCarroll and Stan Gronthos, have been working on a laboratory-based model for actual treatment in humans. As part of this research Dr Ellis found that stem cells derived from teeth developed into cells that closely resembled neurons.

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Stem Cells Taken From Teeth Can Make Brain-like Cells

Novartis abandons plans to buy Gamida Cell

By Stem Cell Treatment

Elbit Medical Technologies Ltd. (TASE:EMTC) and Clal Biotechnology Industries Ltd. (TASE: CBI) announced this morning that talks to sell stem cell cancer treatment developer Gamida Cell have broken down. Novartis AG (NYSE:NVS; LSE: NOV; SWX: NOVZ) had been in talks to acquire Gamida Cell for $200-300 million cash with the potential for a further three hundred million dollars in milestone payments and royalties. Sources inform "Globes" that Novartis decided not to approve the deal.

It is not clear what is Novartis's reason for pulling out of the deal. Novartis had never publicly acknowledged that there were talks in the first place, although they had signed a memorandum of understanding including the exact financial conditions of the deal.It is unusual for a deal to reach such an advanced stage and not be realized, even though this was a very advanced deal and it was related to future strategic directions.

The main casualties of the decision were Gamida Cell's shareholders - Elbit Medical (30%) and Clal Biotechnology (22%).

Gamida Cell has proprietary technology for growing the number and density of stem cells within a specific blood sample. This capability could be a basis for all stem cell activity. The company seeks to enhance umbilical cord blood donations for implants to cure blood cancer in adults. Currently, umbilical cord blood can only be used for implant in people weighing less than 45 kilograms.

Gamida-Cell's first product was jointly developed with Teva Pharmaceutical Industries Ltd. (NYSE: TEVA; TASE: TEVA) but the US Food and Drug Administration (FDA) retroactively tightened clinical trial requirements rendering the product's development uneconomical. The company is developing what it says is an improved product in the same field. The product is undergoing clinical trials, and because of its expected improved efficacy, justifies the high development cost.

Gamida-Cell is also considering an IPO on Wall Street.

Published by Globes [online], Israel business news - http://www.globes-online.com - on May 1, 2014

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Novartis abandons plans to buy Gamida Cell

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