UC Davis Researcher Spearheads Groundbreaking Stem Cell Find

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SACRAMENTO (CBS13) The UC Davis Medical Center has the first lab in the country to find stem cells in an adult bladder.

Stem cells from humans have been turned into almost any other tissue in the body, said Dr. Eric Kurzrock from the UC Davis Institute for Regenerative Cures.

But Kurzrock says nobody has ever done it with a bladder and this research, now published in the Stem Cells Translational Medicine scientific journal, could be monumental for science.

You could potentially use bladder cells that we created to make a new bladder, Kurzrock said.

This could help children born with spina bifida, and adults with a diseased bladder or bladder cancer.

Before this revelation, a doctors only option was to use the intestine to make the bladder larger.

In this case, we could use an engineered bladder, Kurzrock said.

It took a team 10 years to publish the project, because as Kurzrock says roadblocks are just part of the research process.

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UC Davis Researcher Spearheads Groundbreaking Stem Cell Find

Stem cell scientists reveal 'unethical' work pressures

From "paradigm changer" to "sloppy and irresponsible". In just two months, two papers revealing a simple way to turn adult cells into embryonic-like stem cells went from being heralded as ground-breaking to being investigated over their credibility.

Stem cell research is touted as the way to a medical revolution, but all too often accusations of poor practice arise. To glean some insight into why, New Scientist asked 1000 stem cell researchers from around the world to answer an anonymous survey about the pressures of their work. More than 110 replied. Some admitted to faked results, others told of unethical behaviour from superiors, and several placed the blame on high-profile journals.

Just over half believe stem cell research is under greater scrutiny than other biomedical fields. "It is because the implications for therapeutics are greater than in other areas," said one researcher. Almost a fifth said this affects their work. Some said it made them more rigorous, while others said they feel forced to find clinical applications too soon.

Sixteen per cent said they have felt pressure to submit a paper that was incomplete or contained unverified information. "There is a tremendous pressure to publish, in order to receive funding. Shortcuts are, therefore, not unusual," said one respondent. "It happens when we know competitors are going to publish the same story," admitted a principal investigator.

Several researchers said they felt pressure to publish or perish. "You have to rush things out or miss critical career fellowships," said one.

Three people said they had felt pressure from peers or superiors to falsify data, or to do something they consider unethical, and five people said "yes" when asked if they or a colleague had ever falsified or augmented data that ended up in a published paper. "I know of numerous instances where fellows with, at times, the knowledge of their mentors, have published falsified data," said one professor.

View a pdf of the full results of the survey

Superiors received some of the blame. "Supervisors and mentors get very excited about data, but some people then become scared to tell them it could not be validated later," said an assistant professor. One postdoc blamed mistakes in his lab's papers on inadequate handling of medical statistics. One professor said: "Sometimes one's job is called into question, and superiors have been known to try and force premature publication and take credit for findings... when they don't even know the content of the work."

Misinterpretation of results was a common concern. "[People] deliberately ignore inconvenient data in order to support their likely erroneous conclusions," said one assistant professor.

The results echo a 2009 study that spanned all scientific fields, says Ivan Oransky, co-founder of website Retraction Watch. In that, 2 per cent admitted to falsification or fabrication, and about a third admitted to other questionable research practices.

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Stem cell scientists reveal 'unethical' work pressures

Embryonic stem cells: Reprogramming in early embryos

9 hours ago Embryonic stem cells (ESCs) established from an interphase 2-cell SCNT blastocyst (magnification 40x). Credit: Mitalipov laboratory at OHSU

An Oregon Health & Science University scientist has been able to make embryonic stem cells from adult mouse body cells using the cytoplasm of two-cell embryos that were in the "interphase" stage of the cell cycle. Scientists had previously thought the interphase stagea later stage of the cell cyclewas incapable of converting transplanted adult cell nuclei into embryonic stem cells.

The findings by OHSU's Shoukhrat Mitalipov, Ph.D., and his team could have major implications for the science of generating patient-matched human embryonic stem cells for regenerative medicine. Human embryonic stem cells are capable of transforming into any cell type in the body. Scientists believe stem cell therapies hold promise for someday curing or treating a wide range of diseases and conditionsfrom Parkinson's disease to cardiac disease to spinal cord injuriesby replacing cells damaged through injury or illness.

Mitalipov's findings will be published March 26 in the online edition of Nature. If the new findings in mice hold true for humans, it could significantly help efforts to make rejection-proof human embryonic stem cells for regenerative therapies. That's because embryonic cells that Mitalipov's team used for reprogrammingcells in the "interphase" stageare more accessible than the traditional egg cells that are in short supply. Scientists previously had believed embryonic stem cells were capable of being produced only using the metaphase stage of egg cytoplasm.

Embryonic stem cells can be made using a process called somatic cell nuclear transfer, or SCNT, in which the nucleus from an adult cell is transferred into the cytoplasm of an unfertilized egg cell. The cytoplasmic machinery then "reprograms" that nucleus and cell into becoming an embryonic stem cell capable of transforming to any type of cell in the body.

"It has always been thought that this capacity for reprogramming ended with metaphase," said Mitalipov, senior scientist at OHSU's Oregon National Primate Research Center. "Our study shows that this reprogramming capacity remains in the later embryonic cell cytoplasm even during interphase. It looks like the factors continue working and they efficiently reprogram the cellsjust as they do in metaphase."

Many scientists have attempted to reprogram cells by interphase cytoplasm. Mitalipov and his team found success by carefully synchronizing the cell cycles of the adult cell nucleus and the recipient embryonic cytoplasm. Both had to be at an almost identical point in their respective cell cycles for the process to work, Mitalipov said.

"That was the secret," Mitalipov said. "When we did that matching, then everything worked."

Mitalipov said the next step to further his research will be to test the process in rhesus macaques.

Mitalipov has become a world scientific leader in embryonic stem cell research and in somatic cell nuclear transfer. He recently was named the director of a newly created research center at OHSUthe Center for Embryonic Cell and Gene Therapy. The center will help Mitalipov and his team accelerate their research, with expanded support from private philanthropy.

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Embryonic stem cells: Reprogramming in early embryos

Okyanos Heart Institute Announces Completion of Investment Funding

Freeport, Bahamas (PRWEB) March 18, 2014

Okyanos Heart Institute, whose mission it is to bring a new standard of care and a better quality of life to patients with coronary artery disease (CAD) using adult stem cell therapy, announced today it has raised $8.9 million in its Series B offering. Passion Group founder Ali Shawkat led the round and is a visionary entrepreneur-investor with success in a diverse set of industries including cellular services, telecom, media and healthcare.

Okyanos has the vision, medical leadership, adult stem cell technology and business model to better the lives of millions of patients, their families and society, said Shawkat. Cell therapy promises to be a new pillar of medicine as it is based on the natural biology of the body.

"This funding brings Okyanos' total funding to $14.2 million. Financial strength is integral to our commitment to treat patients with cardiac cell therapy at the highest standards of safety and care, stated Matthew Feshbach, co-founder and CEO of Okyanos.

Okyanos' cardiac cell therapy utilizes cells known as adipose-derived stem and regenerative cells (ADRCs), processed by Cytori Therapeutics (NASDAQ: CYTX) Celution system, a technology which has been approved and is commercially available in Europe, Australia, New Zealand, Singapore and other international jurisdictions for various indications of use.

The company has procured a state-of-the-art Philips cath lab and is building out a center of excellence capable of treating over 1000 patients per year in Freeport, The Bahamas. Based on the recommendations of the Bahamas Stem Cell Task Force, which thoroughly studied the safety and efficacy of adult stem cell therapy, the Bahamas passed stem cell legislation in August, 2013.

Feshbach further stated, We have a sophisticated, entrepreneurial group of investors who are like-minded in our purpose to safely improve the quality of life of patients suffering from illnesses such as CAD, using adult stem cells derived from adipose (fat) tissue, added Feshbach. We appreciate the significant leadership and support of Mr. Shawkat who shares the Okyanos commitment.

The company will begin treating patients with coronary artery disease using their own stem cells in the summer of 2014.

About Okyanos Heart Institute: (Oh key AH nos) Based in Freeport, The Bahamas, Okyanos Heart Institutes mission is to bring a new standard of care and a better quality of life to patients with coronary artery disease using cardiac stem cell therapy. Okyanos adheres to U.S. surgical center standards and is led by Chief Medical Officer Howard T. Walpole Jr., M.D., M.B.A., F.A.C.C., F.S.C.A.I. Okyanos Treatment utilizes a unique blend of stem and regenerative cells derived from ones own adipose (fat) tissue. The cells, when placed into the heart via a minimally-invasive procedure, can stimulate the growth of new blood vessels, a process known as angiogenesis. Angiogenesis facilitates blood flow in the heart, which supports intake and use of oxygen (as demonstrated in rigorous clinical trials such as the PRECISE trial). The literary name Okyanos, the Greek god of rivers, symbolizes restoration of blood flow. For more information, go to http://www.okyanos.com.

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Okyanos Heart Institute Announces Completion of Investment Funding

Stem Cell Therapy | Animal Medical Center

The unique ability of stem cells to mature into cells with specialized functions makes them useful for repairing certain body tissues damaged by injury or disease. The Animal Medical Center is now harnessing the power of these cells by offering stem cell therapy for the treatment of chronic arthritis. The AMC is offering this service through a partnership with Vet-Stem, Inc., an innovator in veterinary regenerative cell medicine.

Stem cell therapy uses an animals own primitive (stem) cells which are capable of dividing and differentiating into a variety of cell types (such as cartilage, bone, or muscle). In areas of injury or disease, stem cells respond to signaling to allow healing and promote regeneration of injured tissues. The most common clinical application for stem cell therapy is currently chronic arthritis.

The process involves three key steps over a three-day period:

Vet-Stem, Inc. is also developing protocols to use stem cell technology as therapy for other conditions in the near future, such as cerebral and myocardial infarction and immune-mediated, renal, neurologic, and hepatic diseases.

Stem cell therapy at The AMC is being directed by Dr. Pamela Schwartz. A Staff Surgeon at The Animal Medical Center, Dr. Schwartz received her board certification in 2008. She has an interest in stem cell therapy and became credentialed in Vet-Stem Regenerative Stem Cell Therapy in October 2007.

The AMC has used stem cell therapy to treat several dogs with pain associated with chronic osteoarthritis. The best results have been noted in dogs that had been experiencing a high level of pain that could not be relieved with medication.

To find out if your dog is a candidate for stem cell therapy, contact the appointment desk at 212-838-7053 to schedule a consultation with Dr. Schwartz.

Read an article from the New York Post on stem cell therapy.

Read a behind the scenes account of stem cell surgery at The AMC.

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Stem Cell Therapy | Animal Medical Center

A Study of Protein Synthesis In Stem Cells Conducted For The First Time

By Liisa Vexler

Scientists at the Children's Medical Center Research Institute, UT Southwestern Medical Center, Texas, have conducted a breakthrough piece of research into protein synthesis in adult stem cells. The research, previously not possible to conduct, has linked certain cancers with mutations affecting protein synthesis.

The process used an antibiotic called puromycin, in modified form, to aid in measuring the quantity of protein synthesized in the body. Research revealed that protein is produced at a different rate per hour for different types of blood cells. It was also noted that much lower amounts of protein are synthesized by stem cells than other cells (blood-forming). The research, conducted on mice, concluded that when ribosome, a genetic mutation involved in making protein, was present the production of protein in stem cells diminished by 30%. Conversely, in another experiment the tumor-suppressor gene P-ten was removed in an attempt to increase protein synthesis, resulting in an impairment of stem cell function. These findings conclude that protein synthesis for blood forming stem cells needs to be well regulated or else they will not function efficiently. A member of the team, Dr. Morrison, observed to his amazement that breeding Pten mutant mice with ribosomal mutant mice returned stem cell function to normal, leading to either a complete block or delay on the development of Leukaemia. Dr. Morrison is of the view that, all of this happened because protein production in stem cells was returned to normal. It was as if two wrongs made a right. The findings are thought to open the door to a number of similar tests for the many kinds of cells in the human body, making it possible to study protein synthesis for each. The research is thought to be important for understanding the differences in the rates and ways that protein in synthesized in cells and what this means for cellular survival.

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A Study of Protein Synthesis In Stem Cells Conducted For The First Time

Researchers find stem cells remember prior substrates

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

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

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'

Riken Apologizes for Errors in Two Stem Cell Studies

Japans Riken center apologized for errors in a pair of studies that had outlined a simpler, quicker way of making stem cells and said the institute is considering urging the scientists to retract it.

Riken will impose a penalty if misconduct is proven, President Ryoji Noyori said in news conference today. Haruko Obokata, who led the research, and two other Riken researchers in a separate statement on the centers website said they are in talks with co-writers to discuss a retraction.

Government-funded Riken on March 11 said is investigating the two studies that were published in journal Nature in January and said ordinary cells taken from newborn mice could be transformed into stem cells without adding genes. The institute today said it was investigating six images and methods in the research after claims that they looked unnatural or were plagiarized from other studies.

We are communicating with other authors and considering the possibility of retracting the studies, Obokata and the two other researchers, Yoshiki Sasai and Hitoshi Niwa, said in a joint statement on Rikens website today.

Two areas were handled inappropriately, though researchers didnt have intent to falsify data, the institute said on its website. The center is still investigating the rest, it said.

Images used in the studies to show the establishment of the method resemble photos from Obokatas previous studies, Kyodo News reported this week. Another scientist, Teruhiko Wakayama at the University of Yamanashi in Japan who worked on the research said he was no longer sure of the premise of the data he used to establish the experiments and that the studies should be withdrawn for review, public broadcaster NHK reported on March 10.

The probe is a setback for Japan as it tries to push into stem-cell science following Shinya Yamanakas 2012 Nobel Prize. Japan aims to cement its leadership in the field of research, and has pushed through bills that fast-track regulatory approval for cell-based products.

Researchers led by Obokata at the Riken Center for Developmental Biology shocked the cells with a dose of sublethal stress such as mechanical force to trigger a transformation. Obokata worked with institutions including Charles Vacantis laboratory at Brigham and Womens Hospital, Harvard Medical School.

In an embryos early stages, stem cells are pluripotent, meaning they can become any type of tissue in the body. As the embryo develops, the cells begin to specialize, or differentiate, into units for the bodys different structures.

There are several ways to regenerate pluripotent stem cells, including one that uses embryos and one that reprograms matured cells by inserting genes. Last year, Japans Health Ministry cleared the way for the worlds first clinical trial with stem cells made using a separate technique established by Yamanaka, the Nobel Prize winner from Kyoto University.

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Riken Apologizes for Errors in Two Stem Cell Studies

Riken Considers Retracting Two Stem-Cell Studies

Research that outlined a simpler, quicker way of making stem cells may be retracted after one of the scientists involved expressed doubts about the basis for the experiments.

Japans Riken research center is investigating two studies published in the journal Nature in January and is considering options including retracting them, the government-funded organization said in a statement on its website today. Riken will give a briefing on the probe March 14.

Teruhiko Wakayama, who worked on the research at the University of Yamanashi in Japan, said in an interview with public broadcaster NHK yesterday that he was no longer sure of the premise of the data he used to establish the experiments and that the studies should be withdrawn for review. The comments underscore the pressure researchers face amid Japans push into stem-cell science following Shinya Yamanakas 2012 Nobel Prize.

Its a disappointment for the community when such high profile papers may possibly be retracted, said Nissim Benvenisty, director of the stem-cell unit at the Hebrew University in Jerusalem, in an interview. Its reassuring that the investigators in this institute are themselves taking the initiative to look into what might have gone wrong.

The studies found that ordinary cells taken from newborn mice could be transformed into stem cells, the versatile building blocks of the body, without adding genes. Researchers led by Haruko Obokata at the Riken Center for Developmental Biology shocked the cells with a dose of sublethal stress such as mechanical force to trigger a transformation.

The study surprised me when it came out because it contradicted the common sense that we have acquired so far in the field, Benvenisty said. At the same time, this is the beauty of the scientific world, that editors allow publications of papers that contradict common sense to allow novel data to be discussed and understood.

Obokata worked with Wakayama and institutions including Charles Vacantis laboratory at Brigham and Womens Hospital, Harvard Medical School.

Rikens media relations department couldnt immediately be reached. An e-mail to Obokata wasnt immediately answered.

Im not sure what Riken will decide to do, Wakayama said in an e-mail responding to a request for comments.

Japans Prime Minister Shinzo Abe aims to cement the countrys leadership in the field of research and has pushed through bills that fast-track regulatory approval for cell-based products and set new research guidelines. Last year, Japans Health Ministry cleared the way for the worlds first clinical trial with stem cells made using a separate technique fromYamanaka, the Nobel Prize winner from Kyoto University.

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Riken Considers Retracting Two Stem-Cell Studies