Chaiwat Subprasom/Reuters/Corbis

Many companies around the world offer stem-cell treatments to patients with heart disease.

An analysis of clinical studies that use adult stem cells to treat heart disease has raised questions about the value of a therapy that many consider inappropriately hyped.

Early-phase clinical trials have reported that adult stem cells are effective in treating heart attack and heart failure, and many companies are moving quickly to tap into this potentially lucrative market. But a comprehensive study that looked at discrepancies in trials investigating treatments that use patients own stem cells, published this week in the journal BMJ (ref. 1), finds that only trials containing flaws, such as design or reporting errors, showed positive outcomes. Error-free trials showed no benefit at all.

The publication comes as two major clinical trials designed to conclusively test the treatments efficacy are recruiting thousands of patients.

The BMJ paper is concerning because the therapeutic approach is already being commercialized, argues stem-cell researcher Paolo Bianco at the Sapienza University of Rome. Premature trials can create unrealistic hopes for patients, and divert resources from the necessary basic studies we need to design more appropriate treatments.

Therapies that use adult stem cells typically involve collecting mesenchymal stem cells from bone marrow taken from the patients hip bone. The cells are then injected back into the patient, to help repair damaged tissue. Original claims that they differentiated into replacement cells have been rejected2, and many clinicians now believe that the cells act by releasing molecules that cause inflammation, with an attendant growth of oxygen-delivering small blood vessels, in the damaged tissue.

The approach has spawned international commercialization of various forms of the therapy, with companies offering treatments for disorders ranging from Parkinsons disease to heart failure. But the effectiveness of such therapies remains unproven.

I have a lot of hope for regenerative medicine, but our results make me fearful.

The BMJ study, led by cardiologist Darrel Francis at Imperial College London, examined 133 reports of 49 randomized clinical trials published up to April last year, involving the treatment of patients who had had a heart attack or heart failure. It included all accessible randomized studies, and looked for discrepancies in design, methodology and reporting of results.

Excerpt from:
Doubts over heart stem-cell therapy : Nature News & Comment

Karen Weintraub, Special for USA TODAY 2:49 p.m. EDT April 30, 2014

A study in "Nature" said researchers showed that they could repair damaged hearts by injecting versatile stem cells into macaque monkeys, like this one in Thailand.(Photo: Apichart Weerawong, AP)

Two new studies out today show both the incredible promise of stem cell research and its current limitations.

In one, published in the journal Nature, researchers showed that they could repair damaged hearts by injecting these versatile stem cells into macaque monkeys. Heart disease is the leading cause of death, and if the same process can work in people, it could benefit hundreds of thousands a year.

In the other study, published in Science Translational Medicine, five men were able to regrow leg muscles destroyed by accidents or military service. The researchers, from the University of Pittsburgh, inserted into the men's muscles a "scaffold" of muscle tissue from a pig. Through aggressive physical therapy right after the surgery, the men's own stem cells were encouraged to populate the scaffold and substantially rebuild their leg muscles.

Nothing had been able to help these men before, including multiple surgeries and years of physical therapy, said Stephen Badylak, the study's senior author.

"Frankly, most of these patients have been through hell," he said at a Tuesday news conference.

David Scadden, a physician and co-director of the Harvard Stem Cell Institute, said he was impressed with the rigor and promise of both studies.

It's long been a goal of stem cell research to figure out how to help the body regrow damaged tissue, he said, and both studies mark a significant step toward that goal.

Both studies also showed that stem cells respond to cells around them, he said, with the heart cells learning to beat in sync with the monkey cells and the muscle cells learning to go where they were needed. "Once the cells get to a certain point, it appears they can then follow the lead of their neighbors," he said.

Read the original post:
Stem cells used to repair animal hearts and human muscle

Thanks to a study with monkeys, the idea of using stem cells to accomplish heart repair on a clinical scale seems more realistic. Stem cells have shown promise in small-animal models, that is, in mice and rats. Still, it was unclear whether human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) could be produced in adequate numbers, and cryopreserved with sufficient viability, to even approach human application.

In a step up from small-animal models, scientists at the University of Washington used a monkey model of myocardial infarction to test how well hESC-CMs could replace damaged tissue with new heart cells and restore failing hearts to normal function. The scientists injected 1 billion heart muscle cells derived from hESC-CMs into the infarcted muscle of pigtail macaques (Macaca nemestrina). This was 10 times more of these types of cells than researchers have ever been able to generate before.

The researchers found that over subsequent weeks, the stem-cell derived heart muscle cells infiltrated into the damaged heart tissue, then matured, assembled into muscle fibers, and began to beat in synchrony with the macaque heart cells. After three months, the cells appeared to have fully integrated into the macaque heart muscle.

Before this study, it was not known if it is possible to produce sufficient numbers of these cells and successfully use them to remuscularize damaged hearts in a large animal whose heart size and physiology is similar to that of the human heart, said Charles Murry, M.D., Ph.D., professor of pathology and bioengineering, who led the research team that conducted the experiment.

The research team published its results April 30 in Nature, in an article entitled Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. In this article, the authors indicated that their work demonstrated that hESCs can be grown, differentiated into cardiomyocytes, and cryopreserved at a scale sufficient to treat a large-animal model of myocardial infarction.

With further refinements in manufacturing, the scale up to trials in human patients seems feasible, the researchers wrote. Large-animal models are important forerunners to human trials, because they impart real-world rigor to issues such as cell production, delivery, and end-point analyses, while permitting mechanistic studies not possible in patients.

On average, the transplanted stem cells regenerated 40% of the damaged heart tissue. Ultrasound studies of the macaques hearts showed that the ejection fraction, an indication of the hearts ability to pump blood, improved in some of the treated animals but not all. The researchers also found that arteries and veins from the macaques hearts grew into the new heart tissue, the first time it has been shown that blood vessels from a host animal will grow into and nurture a large stem-cell derived graft of this type.

The most concerning complications were arrhythmias that occurred in the weeks after the macaques received the stem cell injections, Dr. Murry said. None of the macaques, however, appeared to have symptoms during these episodes, which disappeared after two to three weeks as the stem cells matured and became more electrically stable.

The researchers also cautioned that in their macaque model, the infarcts they had induced were smaller than the clinically severe infarcts that might benefit most from hESC-CM therapy. The researchers added that larger infarcts, in human hearts, might manifest more arrhythmias.

Because ventricular arrhythmias can be life threatening, they need to be understood mechanistically and managed en route to safe clinical translation, the authors noted. Nevertheless, the extent of remuscularization and electromechanical coupling seen here encourages further development of human cardiomyocyte transplantation as a clinical therapy for heart failure.

Follow this link:
GEN | News Highlights:Human Stem Cells Repair Heart Damage ...

Image Caption: This image shows an implanted graft of cardiac cells derived from human stem cells (green) meshed and beat with primates' heart cells (red). Credit: Murry Lab/University of Washington

April Flowers for redOrbit.com Your Universe Online

When a heart attack occurs, the oxygen-rich blood that normally flows through is interrupted by the blockage in an artery. The longer that blood flow is restricted or cut off, the more tissue and muscle in the area dies or is scarred. The eventual result can be heart failure, especially if one heart attack is followed by another.

In 2013, Harvard Health Publications released a report taking a look at the state of stem cell research into the problem of regenerating heart tissue, and the results were mixed.

A new study from the University of Washington, however, reveals improvement in those results. The findings, published online in Nature, demonstrate that damaged heart muscles in monkeys have been restored by the use of heart cells created from human embryonic stem cells. The exciting implication, according to the research team, is that their approach should also be feasible in humans.

Before this study, it was not known if it is possible to produce sufficient numbers of these cells and successfully use them to remuscularize damaged hearts in a large animal whose heart size and physiology is similar to that of the human heart, said Dr. Charles Murry, UW professor of pathology and bioengineering and director of the UW Center for Cardiovascular Biology, in a recent statement.

Murray, who collaborated with Dr. Michael Laflamme and other colleagues at the UW Institute for Stem Cell & Regenerative Medicine, predicts clinical trials with humans within the next four years.

[ Watch the Video: Regenerating Heart Muscle Damage With Stem Cell Therapy ]

For the study, the researchers induced controlled myocardial infarctions, a type of heart attack, in anesthetized pigtail macaques, by blocking the coronary artery for 90 minutes. This is the accepted practice for studying myocardial infarction in primates.

Coronary artery disease is the primary culprit in myocardial infarctions in humans. The infarcted heart muscle, damaged by a lack of oxygen, does not grow back, leaving the heart less able to pump blood. This often leads to heart failure, the leading cause of cardiovascular death. Researchers hope to use new heart cells created from stem cells in order to restore normal function to the failing heart.

Read the original here:
Heart Muscles Repaired After Heart Attack Using Human Embryonic Stem Cells

It shows for the first time that we can do regeneration at a scale that the world has never seen before, said Dr Charles Murry, professor of pathology and bioengineering, at the University of Washington.

"Before this study, it was not known if it is possible to produce sufficient numbers of these cells and use them to re-muscularise damaged hearts in a large animal whose heart size and physiology is similar to that of the human heart."

Weve shown that (stem cells) will survive and they will organise to form new heart muscle and they will connect with the surrounding cardiac muscle cells and beat in synchrony.

The green area shows the regenerated heart muscle

Currently heart muscle cannot be repaired and people with severe heart failure must wait for a heart transplant.

In the study the team induced heart attacks, in anesthetised macaque monkeys.

Over the course of two weeks they injected one billion heart muscle cells derived from human embryonic stem cells.

The researchers found that the stem cells infiltrated into the damaged heart tissue, matured, and knitted into muscle fibers, before beginning to beat in rhythm with the macaque heart cells.

After three months, the cells had fully integrated into the heart. On average the transplanted stem cells regenerated 40 percent of the damaged heart tissue and improve the ability of the heart to pump blood.

Although the study has been carried out on macaque monkeys, the researchers at the University of Washington said "the approach should be feasible in humans".

Originally posted here:
Stem cell injections may take place of heart swaps

An implanted graft of cardiac cells derived from human stem cells (green) meshed with a monkey's own heart cells (red). Picture: Murry Lab/University of Washington/PA

Stem cell heart repair treatments could be tested on human patients within four years following a ground-breaking study of monkeys.

Scientists successfully restored damaged cardiac muscle in macaque monkeys suffering the after-effects of experimentally induced heart attacks, paving the way to clinical trials.

Researchers injected 1bn immature heart muscle cells derived from human embryonic stem cells into each animals heart.

Over several weeks, the new cells developed, assembled into muscle fibres, and began to beat in correct time. On average, 40% of the damaged heart tissue was regenerated.

It is the first time stem cell therapy for damage caused by heart attacks has been shown to work in a primate.

Lead scientist Prof Charles Murry, director of the Centre for Cardiovascular Biology at the University of Washington in Seattle, said: Before this study, it was not known if it is possible to produce sufficient numbers of these cells and successfully use them to remuscularise damaged hearts in a large animal whose heart size and physiology is similar to that of the human heart.

He expects the treatment to be ready for clinical trials in human patients within four years.

Heart attack symptoms were triggered in the monkeys by blocking the coronary artery the main artery supplying the heart with blood for 90 minutes.

In humans, the reduced blood flow caused by narrowing of the arteries has a similar effect. Lack of blood flow to the heart damages the heart muscle by depriving it of oxygen.

View original post here:
Stem cell breakthrough in treating heart attacks

Stem cells could be used to treat heart disease

6:30am Friday 2nd May 2014 in News

STEM cells taken from bone marrow could be used to treat heart disease by injecting them into damaged tissue, early results show.

Stem cells are cells in the body which have not yet specialised and can become any type.

Oxford University scientists hailed the encouraging evidence in results of 26 small clinical trails involving 1,255 people.

A year or more after treatment, just three per cent of people had died, compared with 15 per cent of people who had not had the procedure.

Hospital readmissions stood at only two in 100 for those testing out the new treatment.

Dr Enca Martin-Rendon, who carried out the study with the Cochrane Heart Review Group, said larger studies would be carried out to get more conclusive evidence.

Go here to see the original:
Stem cells could be used to treat heart disease

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.

Here is the original post:
Protein Discovery Could Boost Efficacy Of Bone Marrow Replacement Treatments

Contact Information

Available for logged-in reporters only

Newswise 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.

The findings have significant clinical implications.

Excerpt from:
Damage Control: Recovering From Radiation and Chemotherapy

Researchers at Columbia Engineering announced today that they have successfully grown fully functional human cartilage in vitro from human stem cells derived from bone marrow tissue. Their study, which demonstrates new ways to better mimic the enormous complexity of tissue development, regeneration, and disease, is published in the April 28 Early Online edition of Proceedings of the National Academy of Sciences (PNAS).

"We've been able -- for the first time -- to generate fully functional human cartilage from mesenchymal stem cells by mimicking in vitro the developmental process of mesenchymal condensation," says Gordana Vunjak-Novakovic, who led the study and is the Mikati Foundation Professor of Biomedical Engineering at Columbia Engineering and professor of medical sciences. "This could have clinical impact, as this cartilage can be used to repair a cartilage defect, or in combination with bone in a composite graft grown in lab for more complex tissue reconstruction."

For more than 20 years, researchers have unofficially called cartilage the "official tissue of tissue engineering," Vunjak-Novakovic observes. Many groups studied cartilage as an apparently simple tissue: one single cell type, no blood vessels or nerves, a tissue built for bearing loads while protecting bone ends in the joints. While there has been great success in engineering pieces of cartilage using young animal cells, no one has, until now, been able to reproduce these results using adult human stem cells from bone marrow or fat, the most practical stem cell source. Vunjak-Novakovic's team succeeded in growing cartilage with physiologic architecture and strength by radically changing the tissue-engineering approach.

The general approach to cartilage tissue engineering has been to place cells into a hydrogel and culture them in the presence of nutrients and growth factors and sometimes also mechanical loading. But using this technique with adult human stem cells has invariably produced mechanically weak cartilage. So Vunjak-Novakovic and her team, who have had a longstanding interest in skeletal tissue engineering, wondered if a method resembling the normal development of the skeleton could lead to a higher quality of cartilage.

Sarindr Bhumiratana, postdoctoral fellow in Vunjak-Novakovic's Laboratory for Stem Cells and Tissue Engineering, came up with a new approach: inducing the mesenchymal stem cells to undergo a condensation stage as they do in the body before starting to make cartilage. He discovered that this simple but major departure from how things were usually? being done resulted in a quality of human cartilage not seen before.

Gerard Ateshian, Andrew Walz Professor of Mechanical Engineering, professor of biomedical engineering, and chair of the Department of Mechanical Engineering, and his PhD student, Sevan Oungoulian, helped perform measurements showing that the lubricative property and compressive strength -- the two important functional properties -- of the tissue-engineered cartilage approached those of native cartilage. The researchers then used their method to regenerate large pieces of anatomically shaped and mechanically strong cartilage over the bone, and to repair defects in cartilage.

"Our whole approach to tissue engineering is biomimetic in nature, which means that our engineering designs are defined by biological principles," Vunjak-Novakovic notes. "This approach has been effective in improving the quality of many engineered tissues -- from bone to heart. Still, we were really surprised to see that our cartilage, grown by mimicking some aspects of biological development, was as strong as 'normal' human cartilage."

The team plans next to test whether the engineered cartilage tissue maintains its structure and long-term function when implanted into a defect.

"This is a very exciting time for tissue engineers," says Vunjak-Novakovic. "Stem cells are transforming the future of medicine, offering ways to overcome some of the human body's fundamental limitations. We bioengineers are now working with stem cell scientists and clinicians to develop technologies that will make this dream possible. This project is a wonderful example that we need to 'think as a cell' to find out how exactly to coax the cells into making a functional human tissue of a specific kind. It's emblematic of the progress being driven by the exceptional young talent we have among our postdocs and students at Columbia Engineering."

The study was funded by the National Institutes of Health (National Institute for Biomedical Imaging and Bioengineering, National Institute for Dental and Craniofacial Research, and National Institute for arthritis and musculoskeletal diseases).

More:
Engineers grow functional human cartilage in lab

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.

Follow this link:
Stem cells from some infertile men form germ cells when transplanted into mice, study finds

hide captionNew research could be promising for infertile men. Scientists were able to make immature sperm cells from skin cells. Their next challenge is to make that sperm viable.

New research could be promising for infertile men. Scientists were able to make immature sperm cells from skin cells. Their next challenge is to make that sperm viable.

Scientists reported Thursday they had figured out a way to make primitive human sperm out of skin cells, an advance that could someday help infertile men have children.

"I probably get 200 emails a year from people who are infertile, and very often the heading on the emails is: Can you help me?" says Renee Reijo Pera of Montana State University, who led the research when she was at Stanford University.

In a paper published in the journal Cell Reports, Pera and her colleagues describe what they did. They took skin cells from infertile men and manipulated them in the laboratory to become induced pluripotent stem cells, which are very similar to human embryonic stem cells. That means they have the ability to become virtually any cell in the body.

They then inserted the cells into the testes of mice, where they became very immature human sperm cells, the researchers report.

"It's much easier than we actually expected," Pera told Shots.

Other researchers caution that there's still much more research that is needed to prove these cells would actually become healthy sperm that could make a baby. But they said the report was intriguing.

"It's one step closer to being able to make sperm in a petri dish," says George Daley, a stem-cell researcher at Harvard. "So I think that's very provocative."

But others worry the techniques could be misused.

Link:
'Provocative' Research Turns Skin Cells Into Sperm

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."

A difficult process to study

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, 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.

The germ cells made from stem cells stopped differentiating in the mice before they produced mature sperm (likely because of the significant differences between the reproductive processes of humans and mice) regardless of the fertility status of the men from whom they were derived. However, the fact that the infertile men's cells could give rise to germ cells at all was a surprise.

Previous research in mice with a similar type of infertility found that although they had germ cells as newborns, these germ cells were quickly depleted. The Stanford findings suggests that the infertile men may have had at least a few functioning germ cells as newborns or infants. Although more research needs to be done, collecting and freezing some of this tissue from young boys known to have this type of infertility mutation may give them the option to have their own children later in life, the researchers said.

See more here:
Stem cells from some infertile men form germ cells when transplanted into mice

Topics: editors picks, family, relationships, science, sex

INFERTILE men could in future be offered a new form of treatment based on converting their skin cells into the sperm-making tissue that is missing in their testicles, scientists have said.

A study has found that it is possible to convert skin cells into male "germ cells" which are responsible for sperm production, using an established technique for creating embryonic-like stem cells, in a form of genetic engineering.

The research, published in the journal Cell Reports, showed that stem cells derived from human skin become active germ cells when transplanted into the testes of mice - even when the man suffers from a genetic condition where he lacks functioning germ cells in his own testes.

Although the mice had functioning human male germ cells, they did not produce human sperm, said Renee Reijo Pera, of Montana State University, who led the study.

"There is an evolutionary block that means that when germ cells from one species are transferred to another, there is not full spermatogenesis unless the species are very closely related," she added.

View post:
Skin cells provide new hope for infertile men

New York, NY (PRWEB) April 29, 2014

The Stem Cell Institute located in Panama City, Panama, welcomes special guest speaker Roberta F. Shapiro, DO, FAAPM&R to its public seminar on umbilical cord stem cell therapy on Saturday, May 17, 2014 in New York City at the New York Hilton Midtown from 1:00 pm to 4:00 pm.

Dr. Shapiro will discuss A New York Doctors Path to Panama.

Dr. Shapiro operates a private practice for physical medicine and rehabilitation in New York City. Her primary professional activities include outpatient practice focused on comprehensive treatment of acute and chronic musculoskeletal and myofascial pain syndromes using manipulation techniques, trigger point injections, tendon injections, bursae injections, nerve and motor point blocks. Secondary work at her practice focuses on the management of pediatric onset disability.

She is the founder and president of the Dayniah Fund, a non-profit charitable foundation formed to support persons with progressive debilitating diseases who are faced with catastrophic events such as surgery or illness. The Dayniah Fund educates the public about the challenges of people with disabilities and supports research on reducing the pain and suffering caused by disabling diseases and conditions.

Dr. Shapiro serves as assistant clinical professor in the Department of Rehabilitation and Regenerative Medicine at Columbia University Medical Center.

Stem Cell Institute Speakers include:

Neil Riordan PhD Clinical Trials: Umbilical Cord Mesenchymal Stem Cell Therapy for Autism and Spinal Cord Injury

Dr. Riordan is the founder of the Stem Cell Institute and Medistem Panama Inc.

Jorge Paz-Rodriguez MD Stem Cell Therapy for Autoimmune Disease: MS, Rheumatoid Arthritis and Lupus

Read the original post:
department IPS Cell Therapy IPS Cell Therapy

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).

See original here:
Sperm precursors made from stem cells of infertile men

PUBLIC RELEASE DATE:

30-Apr-2014

Contact: Leila Gray leilag@uw.edu 206-685-0381 University of Washington

Heart cells created from human embryonic stem cells successfully restored damaged heart muscles in monkeys.

The results of the experiment appear in the April 30 advanced online edition of the journal Nature in a paper titled, "Human embryonic-stem cell derived cardiomyocytes regenerate non-human primate hearts."

The findings suggest that the approach should be feasible in humans, the researchers said.

"Before this study, it was not known if it is possible to produce sufficient numbers of these cells and successfully use them to remuscularize damaged hearts in a large animal whose heart size and physiology is similar to that of the human heart," said Dr. Charles Murry, UW professor of pathology and bioengineering, who led the research team that conducted the experiment.

A physician/scientist, Murry directs the UW Center for Cardiovascular Biology and is a UW Medicine pathologist.

Murry said he expected the approach could be ready for clinical trials in humans within four years.

In the study, Murry, along with Dr. Michael Laflamme and other colleagues at the UW Institute for Stem Cell & Regenerative Medicine, experimentally induced controlled myocardial infarctions, a form of heart attack, in anesthetized pigtail macaques.

The rest is here:
Stem cell therapy regenerates heart muscle damaged from heart attacks in primates

23 hours ago Marbled Salamander, Ambystoma opacum. Location: Durham County, North Carolina, United States. Photograph by Patrick Coin, via Wikipedia.

Imagine filling a hole in your heart by regrowing the tissue. While that possibility is still being explored in people, it is a reality in salamanders. A recent discovery that newt hearts can regenerate may pave the way to new therapies in people who need to have damaged tissue replaced with healthy tissue.

Heart disease is the leading cause of deaths in the United States. Preventative measures like healthful diets and lifestyles help ward off heart problems, but if heart damage does occur, sophisticated treatments and surgical procedures often are necessary. Unfortunately, heart damage is typically irreversible, which is why researchers are seeking regenerative therapies that restore a damaged heart to its original capacity.

We have known for hundreds of years that newts and other types of salamanders regenerate limbs. If you cut off a leg or tail, it will grow back within a few weeks. Stanley Sessions, a researcher at Hartwich College in Oneonta, N.Y., wondered if this external phenomenon also took place internally. To find out, he surgically removed a piece of heart in more than two dozen newts.

"To our surprise, if you surgically remove part of the heart, (the creature) will regenerate a new heart within just six weeks or so," Sessions said. "In fact, you can remove up to half of the heart, and it will still regenerate completely!"

Before the research team dove deeper into this finding, Sessions and his three undergraduate students, Grace Mele, Jessica Rodriquez and Kayla Murphy, had to determine how a salamander could even live with a partial heart. It turns out that a clot forms at the surgical site, acting much like the cork in a wine bottle, to prevent the amphibian from bleeding to death.

What is the cork made of? In part, stem cells. Stem cells have unlimited potential for growth and can develop into cells with a specialized fate or function. Embryonic stem cells, for example, can give rise to all of the cells in the body and, thus, have promising potential for therapeutics.

As it turns out, stem cells play an important role in regeneration in newts. "We discovered that at least some of the stem cells for heart regeneration come from the blood, including the clot," Sessions explained.

This finding could have exciting implications for therapies in humans with heart damage. By finding the genes responsible for regeneration in the newt, researchers may be able to identify pathways that are similar in newts and people and could be used to induce regeneration in the human heart. In fact, a clinical trial performed just last year was the first to use stem-cell therapy to regenerate healthy tissue and repair a patient's heart.

Combining advances in medical and surgical technologies with the basic pathways of heart regeneration in newts could lead to better therapies for humans. Sessions posed this hopeful question: "Wouldn't it be great if we could find a way to activate heart stem cells to bioengineer new heart tissue so that we can actually repair damaged hearts in humans?"

See the rest here:
Stem cells aid heart regeneration in salamanders

Contact Information

Available for logged-in reporters only

Newswise New York, NYApril 30, 2014Researchers at Columbia Engineering announced today that they have successfully grown fully functional human cartilage in vitro from human stem cells derived from bone marrow tissue. Their study, which demonstrates new ways to better mimic the enormous complexity of tissue development, regeneration, and disease, is published in the April 28 Early Online edition of Proceedings of the National Academy of Sciences (PNAS).

Weve been ablefor the first timeto generate fully functional human cartilage from mesenchymal stem cells by mimicking in vitro the developmental process of mesenchymal condensation, says Gordana Vunjak-Novakovic, who led the study and is the Mikati Foundation Professor of Biomedical Engineering at Columbia Engineering and professor of medical sciences. This could have clinical impact, as this cartilage can be used to repair a cartilage defect, or in combination with bone in a composite graft grown in lab for more complex tissue reconstruction.

For more than 20 years, researchers have unofficially called cartilage the official tissue of tissue engineering, Vunjak-Novakovic observes. Many groups studied cartilage as an apparently simple tissue: one single cell type, no blood vessels or nerves, a tissue built for bearing loads while protecting bone ends in the joints. While there has been great success in engineering pieces of cartilage using young animal cells, no one has, until now, been able to reproduce these results using adult human stem cells from bone marrow or fat, the most practical stem cell source. Vunjak-Novakovics team succeeded in growing cartilage with physiologic architecture and strength by radically changing the tissue-engineering approach.

The general approach to cartilage tissue engineering has been to place cells into a hydrogel and culture them in the presence of nutrients and growth factors and sometimes also mechanical loading. But using this technique with adult human stem cells has invariably produced mechanically weak cartilage. So Vunjak-Novakovic and her team, who have had a longstanding interest in skeletal tissue engineering, wondered if a method resembling the normal development of the skeleton could lead to a higher quality of cartilage.

Sarindr Bhumiratana, postdoctoral fellow in Vunjak-Novakovics Laboratory for Stem Cells and Tissue Engineering, came up with a new approach: inducing the mesenchymal stem cells to undergo a condensation stage as they do in the body before starting to make cartilage. He discovered that this simple but major departure from how things were usually? being done resulted in a quality of human cartilage not seen before.

Gerard Ateshian, Andrew Walz Professor of Mechanical Engineering, professor of biomedical engineering, and chair of the Department of Mechanical Engineering, and his PhD student, Sevan Oungoulian, helped perform measurements showing that the lubricative property and compressive strengththe two important functional propertiesof the tissue-engineered cartilage approached those of native cartilage. The researchers then used their method to regenerate large pieces of anatomically shaped and mechanically strong cartilage over the bone, and to repair defects in cartilage.

Our whole approach to tissue engineering is biomimetic in nature, which means that our engineering designs are defined by biological principles, Vunjak-Novakovic notes. This approach has been effective in improving the quality of many engineered tissuesfrom bone to heart. Still, we were really surprised to see that our cartilage, grown by mimicking some aspects of biological development, was as strong as normal human cartilage.

The team plans next to test whether the engineered cartilage tissue maintains its structure and long-term function when implanted into a defect.

The rest is here:
Columbia Engineers Grow Functional Human Cartilage in Lab

Written by Lidia Dinkova on April 30, 2014

After 15 years of University of Miami research on a unique adult bone marrow-derived stem cell and on a process that leaves the cell in a relatively pure form, the university and its tissue bank have partnered with a Marietta, GA, biomedical company to make the stem cell called the MIAMI cell commercially available in July.

Vivex Biomedical Inc. invested in the research and development of the cell and licensed the technology from UM for orthopedic use, said company President and CEO Tracy S. Anderson. Vivex has contracted with the universitys tissue bank to develop the cell for commercial use. The company will pay an undisclosed royalty to UM from sales.

Dr. H. Thomas Temple, professor of orthopedics, vice chair of orthopedic surgery and director of the University of Miami Tissue Bank, said South Florida is a viable market for the MIAMI cell.

Just in bone [regeneration] alone theres an enormous market, and then if you take into consideration all the joint dysfunction that occurs with aging we have a significantly aged population, he said. If you think about the number of trauma cases we have down here where patients have open fractures, I think this has enormous potential.

Not a lot of companies, Dr. Temple said, are keen on investing in stem cells.

A lot of big companies dont want to take the risk on stem cells because they dont understand it, and theyre making a lot of money on other things, he said. The university doesnt have the financial resources to do the development work. They [UM] do a great job of investigating and researching these things, but the development side takes a lot of capital. In order to have a successful product, not only does it have to be really good, you have to have a successful market, so they [Vivex] bring in the distribution.

The marrow-isolated adult multi-lineage inducible cell, or MIAMI cell, is unique on two fronts. Its highly inducible and potent partially because it shares genes with embryonic stem cells, and the process used to isolate it allows for the infusion of a purer MIAMI cell concentration.

Generally in other processes, when stem cells are infused, they come with other cells that may be synergistic but more likely antagonistic, Dr. Temple said.

Its a small percentage of that actual layer that are actually stem cells. It may be effective, but this is different, he said. When we provide the cells, we can tell you that 95% of them are really MIAMI cells. Once theyre thawed, 97% to 98% of them are viable. Its really the process that makes them different.

Continue reading here:
UM research lands stem cell deal