Stem Cell Clinic

Researchers find stem cells remember prior substrates

By Stem Cell Medical Center

6 hours ago by Bob Yirka Mesenchymal stem cell displaying typical ultrastructural characteristics. Credit: Robert M. Hunt/Wikipedia

(Phys.org) A team of researchers working at the University of Colorado has found that human stem cells appear to remember the physical nature of the structure they were grown on, after being moved to a different substrate. In their paper published in the journal Nature Materials, the researchers describe how they grew human stem cells on different substrates. In so doing, they discovered that the stem cells continued to express certain proteins related to a substrate even after its hardness was changed.

Scientists have known for some time that stem cells respond to their environment as they growthose grown on hard material, such as glass or metal for example, are more amenable to growing into bone cells. In this new effort, the researchers sought to discover if changes to a stem cell brought about by environment are retained if the stem cell is moved to a different environment.

To find out, the researchers used mesenchymal cells which are known to be able to grow into almost any human body part. They placed the stem cells on a stiff substrate then moved them to one less stiff over differing numbers of days. In so doing, they found that the longer the cells were left on the stiff substrate the more a protein connected to bone growth (RUNX2) was expressed. Conversely, cells that were first placed on a soft surface and subsequently moved to a hard surface demonstrated a tendency to develop either bone or adipogenic tendencies.

In another experiment, the researchers applied the stem cells to a substrate coated with a phototunable hydrogelit grows softer when exposed to lightusing it allowed for changing the stiffness of the substrate without having to move the cells. Using this approach the team found that if the cells were allowed to grow on the gel in its stiff state, for just one day, switching to a soft state caused the expression of RUNX2 to cease immediately. When they allowed the cells to grow for ten days on the stiff base, however, before switching to a soft one, expression of RUNX2 continued for another ten days before finally ceasing. This shows, the researchers contend, that stem cells have a memory component that is not yet understood.

The researchers note that their findings could be applied to other stem cell research areas such as cases where unintentional consequences may be arising in experiments due to the stiffness of the substrate in which they are being grown. It also raises the question of whether other environmental factors might be impacting cell growth and if so, if they have a memory component as well.

Explore further: Heart cells respond to stiff environments

More information: Mechanical memory and dosing influence stem cell fate, Nature Materials (2014) DOI: 10.1038/nmat3889

Abstract We investigated whether stem cells remember past physical signals and whether these can be exploited to dose cells mechanically. We found that the activation of the Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding domain (TAZ) as well as the pre-osteogenic transcription factor RUNX2 in human mesenchymal stem cells (hMSCs) cultured on soft poly(ethylene glycol) (PEG) hydrogels (Young's modulus E ~ 2 kPa) depended on previous culture time on stiff tissue culture polystyrene (TCPS; E ~ 3 GPa). In addition, mechanical dosing of hMSCs cultured on initially stiff (E ~ 10 kPa) and then soft (E ~ 2 kPa) phototunable PEG hydrogels resulted in either reversible orabove a threshold mechanical doseirreversible activation of YAP/TAZ and RUNX2. We also found that increased mechanical dosing on supraphysiologically stiff TCPS biases hMSCs towards osteogenic differentiation. We conclude that stem cells possess mechanical memorywith YAP/TAZ acting as an intracellular mechanical rheostatthat stores information from past physical environments and influences the cells' fate.

Journal reference: Nature Materials

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Researchers find stem cells remember prior substrates

Registration of PH stem cell group revoked

By Uncategorized

MANILA - The Securities and Exchange Commission (SEC) revoked the corporate registration of the Philippine Society for Stem Cell Medicine (PSSCM) for submitting fabricated endorsement from the Professional Regulation Commission (PRC).

In a five-page order, SEC acting director Ferdinand Sales said the PSSCM committed fraud in procuring its Certificate of Incorporation.

He said that as required under Section 17 of the Corporation Code, the PSSCM submitted a favorable endorsement from the PRC to support its application for corporate registration.

But he said the SEC found that the 2nd PRC Indorsement dated Feb. 20, 2013 submitted by PSSCM was falsified.

Considering the submission of a falsified PRC endorsement, there is fraud in procurement of respondents certificate of registration. The falsified document was relied upon by this Commission in approving the registration application of the respondent, Sales noted.

He added that had the SEC known about such defect early on, it would have not accepted and approved the registration application of the respondent.

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Registration of PH stem cell group revoked

PMA head, 4 other doctors probed by PRC over alleged fraud, forgery

By Uncategorized

MANILA, Philippines The president of the Philippine Medical Association (PMA) and his four predecessors have been slapped with ethics cases before the Professional Regulation Commission (PRC) for alleged fraud in the registration of the Philippine Society for Stem Cell Medicine (PSSCM) in the Securities and Exchange Commission.

In a statement on Sunday, PRC Chair Teresita Manzala said she has directed the Professional Regulatory Board of Medicine (PRBOM) to file cases against doctors Leo Olarte, Bu Castro, Rey Melchor Santos, Oscar Tinio and Jose Sabili for forging her signature in the incorporation of the PSSCM.

The Commission directed the PRBOM to initiate the filing of a case of unprofessional, dishonorable and unethical conduct against the five incorporators, said Manzala, adding that a case was already pending before the PRC legal division.

Olarte, Castro, Santos, Tinio and Sabili were identified as the incorporators of the PSSCM, whose registration has been revoked by the SEC.

Investigation showed the doctors submitted an application to the SEC for the corporations registration in February 2013. As part of the procedure, PRBOM sent a communication to the five incorporators requiring them to submit pertinent documents but did not receive any response from the doctors. Without the documents, the PRBOM instead placed the application papers on hold. It never submitted the application papers and the required PRC endorsement to the SEC for final approval, said Manzala.

But several months later, the board received information that the PSSCM was able to register with the SEC, based on an endorsement signed by the PRC chair.

On examination of the supposed PRC endorsement, it was noted that the reference regulatory law used was the Philippine Veterinary Law of 2004, instead ofthe Medical Act of 1959, and there appeared a signature of the PRC chair, she said.

Manzala said three of the incorporators, whom she did not identify, denied participation in obtaining the SEC registration and pointed to Dr. Mike Aragon, the PMA spokesperson, as the one responsible for registering the organization at SEC.

In a notarized affidavit submitted to the PRBOM, Aragon admitted he was appointed to register the corporation at SEC but added that he paid P15,000 to a trading company to file the necessary documents needed for the incorporation of PSSCM. He denied involvement in the actual processing of the SEC papers after making the payment.

Manzala submitted a complaint to the SEC, charging her signature was forged in August 2013.

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PMA head, 4 other doctors probed by PRC over alleged fraud, forgery

Doctors charged with fraud

By Stem Cell Doctors

Teresita Manzala, chair of the Professional Regulations Commission (PRC), has accused five prominent doctors of committing fraud to secure approval for a corporation that they set up.

Leo Olarte, Bu Castro, Rey Melchor Santos, Oscar Tinio and Jose Asa Sabili allegedly forged Manzalas signature so their corporation could be approved by the Securities and Exchange Commission (SEC).

Olarte is the current president of the Philippine Medical Association (PMA), while the others are past presidents of the group.

The SEC has revoked the registration of the Philippine Society for Stem Cell Medicine Inc. (PSSCM), the company the five doctors registered.

Criminal and administrative charges may be filed against Olarte et al. for allegedly forging the PRC heads signature.

PSSCMs stated purpose is to organize and operate an organization that will advocate the development and propagation of stem cell technology, including but not limited to information dissemination, research, fora, seminars and other related activities to support the above-mentioned.

After receiving the PSSCM application, the SEC asked its incorporators to submit a favorable endorsement from the PRC because of the medical nature of the proposed company.

Complying with the SEC order, the incorporators submitted a document which bore the signature presumed to be that of PRC Chair Manzala.

The document states the PRC went over the provisions of PSSCMs articles of incorporation and found these consistent with the PRC Modernization Law of 2000.

On the basis of the alleged endorsement, the SEC approved the application.

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Doctors charged with fraud

Nobel laureate calls handing of stem cell research data 'sloppy'

By Stem Cell Medical Center

The Nobel Prize-winning head of a Japanese institute whose scientists' work on stem cells was hailed as a game-changer in the field of medical biology called the lead researcher's handling of the data "extremely sloppy" and "irresponsible".

Two papers published in the journal Nature in January detailed a simple way to reprogram mature animal cells back into an embryonic-like state that allows them to generate many types of tissue, offering hope for a simpler way to replace damaged cells or grow new organs in humans.

But other scientists have been unable to replicate the research's results since then and there have been indications of problems with its data and images.

"The problem here is one immature researcher collected a huge amount of research data, and her handling of data was extremely sloppy and irresponsible," president of Japanese research institute RIKEN Ryoji Noyori told a news conference.

"I would like to offer my apology for the Nature articles, having brought into question the credibility of the science community," said Noyori, bowing deeply.

Noyori, who won a Nobel prize for chemistry in 2001, was referring to Haruko Obokata, 30, a lead author of the papers who became an instant celebrity in Japan after they were published.

A written statement from Obokata and two other RIKEN researchers made available at the news conference said they are discussing the possible withdrawal of the papers with other co-authors.

Another scientist on the team, Teruhiko Wakayama of the University of Yamanashi, has already called for the papers to be withdrawn.

"It is no longer clear what's right," Wakayama told public broadcaster NHK on Monday.

The news conference was called to release the interim findings of investigation on the controversy by a panel of experts from within and outside RIKEN.

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Nobel laureate calls handing of stem cell research data 'sloppy'

Fairfield vet hospital performs stem cell treatments

By Stem Cell Treatment

A Fairfield veterinary hospital is using stem cell treatment to help ailing dogs suffering from joint pain and even hip dysplasia.

Officials said Woodridge Veterinary Hospital is one of the few places that have performed these procedures.

On Friday Bosco, an 11-year-old Labrador, was in for surgery on his arthritic knees.

Doctors took fat out of Bosco, extracted the stem cells and then injected the stem cells back into Boscos knees.

Doctors said Bosco will have a little bit of swelling after the procedure but in four or five weeks he should be feeling much better.

Dr. Roberto Legorreta explained how stem cells are naturally used in the body.

"Every time that a trauma happens or anything that happens in our body, the stems cells are what get activated to regenerate that tissue. That's how we heal," Legorreta said.

Legorreta touched on the importance of this procedure and the excitement that goes along with it.

"I think this is the future of medicine, truly, in many many ways, and we're glad to be at the forefront of that, Legorreta said.

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Fairfield vet hospital performs stem cell treatments

FDA's Regulation of Regenerative Medicine including Stem Cell Treatments, Tissue Engineering, Etc.

By Stem Cell Medicine

Course Description: Regenerative medicine focuses on harnessing the power of ones own stem cells and regenerative capabilities to restore function to damaged cells, tissues and organs. In April 2006, the U.S. Food and Drug Administrations (FDA) implemented regulations governing the use of human cells, tissues, and cellular and tissue-based products (HCT/Ps) in humans including bone, ligament, skin, dura mater, stem cells, cartilage cells, and various other cellular and tissue-based products. Currently, there is an ongoing debate in the industry on how such therapies should be regulated by FDA or under the practice of medicine, under federal law or state law, and as drugs or simply biologics.

This 2-day interactive seminar on FDA regulations of regenerative medicine will cover:

-How FDA is currently regulating regenerative therapies and products intended for both human and veterinary use. -The distinction being made between human regenerative products and their regulation as drugs, biologics, devices, and combination products. -The New Drug Application (NDA) and the Biologic License Application (BLA) review and approval processes including a discussion of available options, application components, relevant meetings, timing, costs and approval requirements. -The option for obtaining designation and approval as Orphan Drug Product. -Designing and conducting appropriate clinical trials to support the approval of regenerative therapies. -FDAs regulation of some regenerative medicine products and accessories as Medical Devices. -The Current Good Manufacturing Practices (cGMPs) and Good Laboratory Practices (GLPs) being applied by FDA to human regenerative products. -The labeling and marketing of regenerative products and therapies. -The potential for enforcement action and recommendations for mitigating that risk. -The current regulation of veterinary cellular treatments including autologous, allogeneic and xenogeneic cellular products in the United States.

Learning Objectives: Participants who attend this course on FDA regulation of regenerative medicines will leave with a comprehensive understanding of:

-How FDA regulates regenerative treatments and therapies? -The HCT/P Criteria and Minimal Manipulation Standard. -The Drug and Biological Approval Process. -Regenerative Products as Medical Devices. -How to Design Appropriate Clinical Trials? -Applicable cGMPs and cGLPs. -Marketing Exclusivity and Patent Restoration. -Product Labeling, Marketing and Advertising. -FDA and other Federal Agency Enforcement Action. -The Regulation of Veterinary Regenerative Medicine. -The New Animal Drug Application (NADA) Process. -Veterinary User Fees and Waivers.

Who will benefit: This course is designed for professionals in stem cell, biotech, pharmaceutical and animal drug companies, veterinary hospitals and clinics. The following personnel will find this session valuable:

-Senior quality managers -Quality professionals -Regulatory professionals -Compliance professionals -Production supervisors -Manufacturing engineers -Production engineers -Design engineers -Labelers and Private Labelers -Contract Manufacturers -Importers and Custom Agents -U.S. Agents of Foreign Corporations -Process owners -Quality engineers -Quality auditors -Document control specialists -Record retention specialists -Medical affairs -Legal Professionals -Financial Advisors and Institutional Investors -Consultants, Inspectors and cGMP Experts

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FDA's Regulation of Regenerative Medicine including Stem Cell Treatments, Tissue Engineering, Etc.

Academic social network ResearchGate aids debunking of stem cell study

By Stem Cell Medicine

5 hours ago Mar. 14, 2014 - 3:36 AM PDT

ResearchGate, the 4-million-strong academic social network, has just scored a major victory in its quest to turn the research process upside-down its platform proved instrumental in the debunking of a major stem cell study, which on Friday resulted in a very apologetic roll-back from the Japanese institute that put out the original study.

The original study came out in Nature, the peer-reviewed scientific journal, earlier this year. It purported to show that it was possible to turn normal blood cells into master stem cells by dipping them in a mild acid solution. Stem cells hold great promise for the future of medicine, but theres a lot of controversy around current harvesting techniques, particularly when embryos are involved, and this would have provided a terrific workaround.

Unfortunately, while the Riken institutes research promised great things, other researchers found themselves unable to reproduce the results. One, a Hong Kong professor of regenerative medicine named Kenneth Lee, used his ResearchGate profile to publish his and his students findings, demonstrating a failure to get this technique to work.

There had been a good deal of grumbling about the Nature paper, but Lees ResearchGate publication provided the final straw and Riken admitted the original Nature papers contained errors. One of the key researchers there has now had her research suspended, and investigations are underway at both Riken and Nature.

This is what I was dreaming of, ResearchGate CEO Ijad Madisch told me. Indeed, Madisch has long advocated the advantages of post-review over pre-peer review.

Rather than the traditional system, where a paper is submitted to a journal like Nature and pored over for months by a couple of reviewers, he wants to see a system where all research is published openly and immediately not only does this bring more eyes to the research, but it also means that unsuccessful results get as good an airing as the successful ones. Thats something that should save other researchers an awful lot of time.

Bill Gates likes this approach, which is why he has poured millions into ResearchGate. And, although the discussion around it occurred in more places than just ResearchGate, the stem cell episode provides a good deal of validation.

According to Madisch, researchers who have found it difficult to reproduce the results of published papers have generally had trouble getting as much attention as those behind the published paper the press, certainly, are keener to trumpet a study that has been peer-reviewed than something that may come from a hater and that journalists feel unable to evaluate themselves.

The excitement around Lees activities on ResearchGate led the startup to speed up the completion of a new feature called Open Review, which is designed to make it easier for users to give open feedback to papers published on the network. The feature combines a structured feedback mechanism with commenting facilities.

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Academic social network ResearchGate aids debunking of stem cell study

New cell line should accelerate embryonic stem cell research

By Stem Cell Medicine

1 hour ago by Michael Mccarthy Dr. Carol Ware at work in her laboratory at the Institute for Stem Cell and Regenerative Medicine. Credit: Bryan Donohue

Researchers at the University of Washington have successfully created a line of human embryonic stem cells that have the ability to develop into a far broader range of tissues than most existing cell lines.

"These cells will allow us to gain a much greater understanding of normal embryonic development and have the real potential for use in developing ways to grow new tissues and organs for transplantation," said Carol Ware, a professor in the UW Department of Comparative Medicine and lead author of a paper describing the new cell line appearing in the March 10 issue of the journal Proceedings of the National Academy of Sciences.

The cells, called nave embryonic stem cells, normally appear at the earliest stages of embryonic development and so retain the ability to differentiate in all the different types of cells of the human bodya capacity called pluripotency.

Researchers had been able to develop naive cells using mouse embryonic stem cells but to create naive human embryonic stem cells has required inserting a set of genes that force the cells to behave like naive cells.

While these "transgenic" cells are valuable research tools, the presence of the artificially introduced genes meant the cells will not develop as normal embryonic cells would nor could they be safely used to create tissues and organs for transplantation.

In an article, Ware and her colleagues from the UW Institute for Stem Cell and Regenerative Medicine describe how they successfully created a line of naive human embryonic stem cells without introducing an artificial set of genes.

They first took embryonic stem cells that are slightly more developed, called primed stem cells, and grew them in a medium that contained factors that switched them backor "reverse toggled" themto the naive state.

They then used the reverse toggled cells to develop a culture medium that would keep them in the naive state and create a stable cell line for study and research.

Then having worked out how to maintain the cells in the naive state, Ware and her colleagues harvested naive cells directly from donated human embryos and cultured them in the maintenance medium to see if they could create a stable cell line that had not undergone reverse toggling. After many tries, they succeeded.

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New cell line should accelerate embryonic stem cell research

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