TAG: "Stem cells"

New reprogramming method makes better stem cells


Findings provide insights into basic biology of stem cells.

Scanning electron micrograph of cultured human neuron from induced pluripotent stem cell. (Image courtesy of Mark Ellisman and Thomas Deerinck, UC San Diego)

A team of researchers from the UC San Diego School of Medicine, Oregon Health & Science University (OHSU), and Salk Institute for Biological Studies has shown for the first time that stem cells created using different methods produce differing cells. The findings, published in today’s (July 2) online issue of Nature, provide new insights into the basic biology of stem cells and could ultimately lead to improved stem cell therapies.

Capable of developing into any cell type, pluripotent stem cells offer great promise as the basis for emerging cell transplantation therapies that address a wide array of diseases and conditions, from diabetes and Alzheimer’s disease to cancer and spinal cord injuries. In theory, stem cells could be created and programmed to replace ailing or absent cells for every organ in the human body.

The gold standard is human embryonic stem cells (ES cells) cultured from discarded embryos generated by in vitro fertilization, but their use has long been limited by ethical and logistical considerations. Scientists have instead turned to two other methods to create stem cells: Somatic cell nuclear transfer (SCNT), in which genetic material from an adult cell is transferred into an empty egg cell, and induced pluripotent stem cells (iPS cells), in which adult cells are reverted back to a stem cell state by artificially turning on targeted genes.

Until now, no one had directly and closely compared the stem cells acquired using these two methods. The scientists found they produced measurably different results. “The nuclear transfer ES cells are much more similar to real ES cells than the iPS cells,” said co-senior author Louise Laurent, Ph.D., assistant professor in the Department of Reproductive Medicine at UC San Diego. “They are more completely reprogrammed and have fewer alterations in gene expression and DNA methylation levels that are attributable to the reprogramming process itself.”

Read more

For more health news, visit UC Health, subscribe by email or follow us on Flipboard.

CATEGORY: NewsComments Off

Heart muscle can regenerate itself in very limited amounts


UCLA researchers are first to directly measure division of cardiomyocytes.

Reza Ardehali, UCLA

Researchers from UCLA’s Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research are the first to directly measure the division of heart muscle cells, proving that while such division is very rare, it does occur.

The study, conducted by assistant professor of cardiology Dr. Reza Ardehali and colleagues, resolves a recent controversy over whether the heart muscle has the power to regenerate itself. The findings are also important for future research that could lead to the regeneration of heart tissue to repair damage caused by disease or heart attack.

The findings were published May 29 in Proceedings of the National Academy of Sciences.

Read more

For more health news, visit UC Health, subscribe by email or follow us on Flipboard.

CATEGORY: NewsComments Off

Link identified between stem cell regulation, development of lung cancer


UCLA findings could lead to new personalized treatments for lung cancer.

UCLA researchers led by Dr. Brigitte Gomperts have discovered the inner workings of the process thought to be the first stage in the development of lung cancer. Their study explains how factors that regulate the growth of adult stem cells that repair tissue in the lungs can lead to the formation of precancerous lesions.

Findings from the three-year study could eventually lead to new personalized treatments for lung cancer, which is responsible for an estimated 29 percent of U.S. cancer deaths, making it the deadliest form of the disease.

The study was published online today (June 19) in the journal Stem Cell. Gomperts, a member of the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and the UCLA Jonsson Comprehensive Cancer Center, collaborated with Manash Paul and Bharti Bisht, postdoctoral scholars and co-lead authors of the study.

Read more

For more health news, visit UC Health, subscribe by email or follow us on Flipboard.

CATEGORY: NewsComments Off

Stem cell therapy shows promise for MS in mouse model


Scientists at UC Irvine, Scripps Research Institute, University of Utah lead project.

Thomas Lane

Mice crippled by an autoimmune disease similar to multiple sclerosis regained the ability to walk and run after a team of researchers led by scientists at UC Irvine, the Scripps Research Institute and University of Utah implanted human stem cells into their injured spinal cords.

The mice started walking a couple of weeks after implantation, and they completely recovered over the next several months, according to the researchers.

Thomas Lane, an immunologist at the University of Utah who started the work when he was at UC Irvine, had never seen anything like it.

“We’ve been studying mouse stem cells for a long time, but we never saw the clinical improvement that occurred,” said Lane, who had received a $4.8 million grant from the California Institute for Regenerative Medicine to support the work.

The mice’s dramatic recovery, which is reported online ahead of print by the journal Stem Cell Reports, could lead to new ways to treat multiple sclerosis in humans. “This is a great step forward in the development of new therapies for stopping disease progression and promoting repair for MS patients,” said co-author Craig Walsh, a UC Irvine immunologist.

View original article

CATEGORY: NewsComments Off

$4M from Broad Foundation will support UCLA research


Two new gifts will benefit faculty in stem cell science and digestive diseases.

Two new gifts from The Eli and Edythe Broad Foundation to UCLA totaling $4 million will fund research in stem cell science and digestive diseases and support the recruitment of key faculty at two renowned research centers.

The gifts bring to $30 million The Broad Foundation’s total support of faculty recruitment and basic and translational research at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA and at the Center for Inflammatory Bowel Diseases at UCLA’s Division of Digestive Diseases.

A $2 million gift to the Broad Stem Cell Research Center adds to The Broad Foundation’s original 2007 gift of $20 million, which has supported faculty and research and launched the Innovation Award program, which furthers cutting-edge research at the center by giving UCLA stem cell scientists “seed funding” for their research projects. The new gift will enable the continuation of the award program, which has yielded a 10-to-1 return on investment with grantees securing additional funding from other agencies, including the National Institutes of Health and more than $200 million in total grants from the California Institute for Regenerative Medicine, the state’s stem cell agency.

“The Broads’ generous support has been essential to the development of new therapies that are currently in, or very near, clinical trials for treating blindness, sickle cell disease and cancer,” said Dr. Owen Witte, director of the Broad Stem Cell Research Center. “The Broad Stem Cell Research Center’s work, supported by critical philanthropic and other resources, is quickly being translated from basic scientific discoveries into new cellular therapies that will change the practice of medicine and offer future treatment options for diseases thought to be incurable, such as muscular dystrophy, autism and AIDS.”

The $2 million gift to the Division of Digestive Diseases builds on nearly $6 million in previous commitments from The Broad Foundation since 2003.

The gifts have enabled the division to develop a comprehensive research and clinical enterprise focused on inflammatory bowel disease, one of only a few such centers in the world.  Earning a multifold return for The Broad Foundation’s initial investments, these grants have enabled investigators to secure $11 million in funding from pharmaceutical companies, the National Institutes of Health and nonprofit foundations.

In addition, The Broad Foundation’s Broad Medical Research Program has provided more than $600,000 in grants to UCLA researchers over the past decade for the study of inflammatory bowel disease.

The new gift will support the Center for Inflammatory Bowel Diseases and research led by Dr. Charalabos “Harry” Pothoulakis, the center’s director. Pothoulakis’ team conducts research aimed at identifying the molecular mechanisms involved in the development of this group of chronic debilitating diseases, for which there is no cure.

The researchers have led the way in revealing how neuropeptides and hormones contribute to inflammatory bowel diseases and the roles of obesity and fat tissue in their development. The team has created a unique human fat cell and fat tissue biobank, and its investigations hold great promise for the development of new drug treatments for Crohn’s disease and ulcerative colitis.

Read more

For more health news, visit UC Health, subscribe by email or follow us on Flipboard.

CATEGORY: NewsComments Off

Damage control: Recovering from radiation and chemotherapy


UC San Diego protein discovery could boost efficacy of bone marrow replacement treatments.

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.

Researchers at the UC 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, Ph.D., 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.”

Read more

For more health news, visit UC Health, subscribe by email or follow us on Flipboard.

CATEGORY: NewsComments Off

Recipe for poor wound healing: bacterial infection plus stress


UC Davis finding may lead to stem cell treatments for chronic wounds.

The stress hormone epinephrine – the source of the “fight-or-flight” response – also heightens stresses at the cellular level, inhibiting wound healing and promoting a state of chronic inflammation that prohibits the body’s stem cells from migrating to a wound to encourage skin regeneration, UC Davis researchers have found.

The research, published in the April issue of the scientific journal Stem Cells Translational Medicine, is the first to show that epinephrine cross-activates other cellular pathways that feed off each other, generating inflammatory proteins in an exaggerated response that impedes wound healing. The research has important implications for the development of new treatments for chronic nonhealing wounds, conditions that affect more than 5 million Americans.

“We have discovered that the pathways activated by the ‘fight-or-flight’ hormone epinephrine and those activated by the presence of bacteria in wounds communicate with one another synergistically, greatly promoting inflammation,” said Mohan R. Dasu, lead author of the study and an associate researcher in the UC Davis Department of Dermatology. “The combination of stress and infection is a recipe for chronic infection.”

Chronic infections are a major global health problem, with annual costs in the United States alone estimated to be more than $23 billion. Nonhealing wounds are particularly common in patients with diabetes, who often develop sores in the foot or leg that become chronic despite intensive antibiotic treatment and sometimes require amputation.

While chronic wounds are traditionally treated primarily with antibiotics, the findings open the way for enhancing therapy with agents that counteract stress hormones. Recent case studies have reported that topical treatment with beta blockers – agents that block adrenergic receptors – have improved chronic skin wounds, although until now, these outcomes have not been well explained.

“Everyone knows that stress is harmful to the body,” said Roslyn Isseroff, professor of dermatology at UC Davis and principal investigator of the study. “Our findings provide a framework for systematically developing new therapeutic strategies that could selectively regulate inflammatory responses in nonhealing wounds.” Isseroff is also chief of the dermatology service at the UC Davis-affiliated Department of Veterans Affairs Northern California Health Care System where she directs a multispecialty wound clinic.

Read more

For more health news, visit UC Health, subscribe by email or follow us on Flipboard.

CATEGORY: NewsComments Off

Cancer stem cells linked to drug resistance


Discovery of previously undefined molecular pathway is step toward novel clinical trial.

David Cheresh, UC San Diego

Most drugs used to treat lung, breast and pancreatic cancers also promote drug resistance and ultimately spur tumor growth. Researchers at the UC San Diego School of Medicine have discovered a molecule, or biomarker, called CD61 on the surface of drug-resistant tumors that appears responsible for inducing tumor metastasis by enhancing the stem cell-like properties of cancer cells.

The findings, published in today’s (April 20) online issue of Nature Cell Biology, may point to new therapeutic opportunities for reversing drug resistance in a range of cancers, including those in the lung, pancreas and breast.

“There are a number of drugs that patients respond to during their initial cancer treatment, but relapse occurs when cancer cells become drug-resistant,” said David Cheresh, Ph.D., Distinguished Professor of Pathology and UC San Diego Moores Cancer Center associate director for innovation and industry alliances. “We looked at the cells before and after they became resistant and asked, ‘What has changed in the cells?’”

Read more

For more health news, visit UC Health, subscribe by email or follow us on Flipboard.

CATEGORY: NewsComments Off

Bone marrow stem cells show promise in stroke treatment


UC Irvine analysis reveals that they trigger repair mechanisms, limit inflammation.

Steven Cramer, UC Irvine

Stem cells culled from bone marrow may prove beneficial in stroke recovery, scientists at UC Irvine’s Sue & Bill Gross Stem Cell Research Center have learned.

In an analysis of published research, neurologist Dr. Steven Cramer and biomedical engineer Weian Zhao identified 46 studies that examined the use of mesenchymal stromal cells – a type of multipotent adult stem cells mostly processed from bone marrow – in animal models of stroke. They found MSCs to be significantly better than control therapy in 44 of the studies.

Importantly, the effects of these cells on functional recovery were robust regardless of the dosage, the time the MSCs were administered relative to stroke onset or the method of administration. (The cells helped even if given a month after the event and whether introduced directly into the brain or injected via a blood vessel.)

“Stroke remains a major cause of disability, and we are encouraged that the preclinical evidence shows [MSCs’] efficacy with ischemic stroke,” said Cramer, a professor of neurology and leading stroke expert. “MSCs are of particular interest because they come from bone marrow, which is readily available, and are relatively easy to culture. In addition, they already have demonstrated value when used to treat other human diseases.”

He noted that MSCs do not differentiate into neural cells. Normally, they transform into a variety of cell types, such as bone, cartilage and fat cells. “But they do their magic as an inducible pharmacy on wheels and as good immune system modulators, not as cells that directly replace lost brain parts,” he said.

In an earlier report focused on MSC mechanisms of action, Cramer and Zhao reviewed the means by which MSCs promote brain repair after stroke. The cells are attracted to injury sites and, in response to signals released by these damaged areas, begin releasing a wide range of molecules. In this way, MSCs orchestrate numerous activities: blood vessel creation to enhance circulation, protection of cells starting to die, growth of brain cells, etc. At the same time, when MSCs are able to reach the bloodstream, they settle in parts of the body that control the immune system and foster an environment more conducive to brain repair.

“We conclude that MSCs have consistently improved multiple outcome measures, with very large effect sizes, in a high number of animal studies and, therefore, that these findings should be the foundation of further studies on the use of MSCs in the treatment of ischemic stroke in humans,” said Cramer, who is also clinical director of the Sue & Bill Gross Stem Cell Research Center.

The analysis appears in the April 8 issue of Neurology. Quynh Vu, Kate Xie and Mark Eckert of UC Irvine contributed to the project, which received support from UC Irvine’s Institute for Clinical & Translational Science through the National Center for Research Resources (grant 5M011 RR-00827-29) and the National Institutes of Health (grants K24HD074722 and R01 NS059909).

View original article

For more health news, visit UC Health, subscribe by email or follow us on Flipboard.

CATEGORY: NewsComments Off

$6.5M gift establishes UC San Diego lab for regenerative ophthalmology


New lab at Shiley Eye Center will investigate advances to reverse vision loss, blindness.

A $6.5 million gift from a grateful patient will create the Richard C. Atkinson Laboratory for Regenerative Ophthalmology in the department of ophthalmology at the UC San Diego Shiley Eye Center. The new lab will investigate cell replacement therapies, tissue engineering and other biomedical advances to reverse vision loss and blindness. Work conducted at the lab will utilize novel stem cell approaches that are consistent with the vision of the newly created Sanford Clinical Stem Cell Center at UC San Diego, which was announced in late 2013.

“This significant gift will provide UC San Diego the foundation for innovation as researchers at the Shiley Eye Center employ a multidisciplinary approach that integrates ophthalmology, vision research, bioengineering, neurosciences and stem cell biology,” said UC San Diego Chancellor Pradeep K. Khosla.

The donor chose to name the laboratory in honor of Richard Atkinson, former University of California president and UC San Diego chancellor, for his lasting impact not only on UC San Diego, but also on the entire UC system. A professor emeritus of cognitive science and psychology, Atkinson served as president of the UC system from 1995 to 2003. Before becoming president, he served for 15 years as chancellor of UC San Diego. He is a former director of the National Science Foundation.

The UC San Diego department of ophthalmology at the Shiley Eye Center is the only academic eye center in the region offering the most advanced treatments across all areas of eye care. World-class clinicians, surgeons, scientists and staff are dedicated to excellence and providing the best possible patient care to prevent, treat and cure eye diseases. The center’s research is at the forefront of developing new methods for diagnosis and treatment of eye diseases and disorders.

Read more

For more health news, visit UC Health, subscribe by email or follow us on Flipboard.

CATEGORY: NewsComments Off

Stem cell findings may offer answers for some bladder defects, diseases


UC Davis discovery opens up opportunities using pluripotent cells.

Eric Kurzrock, UC Davis

For the first time, scientists have succeeded in coaxing laboratory cultures of human stem cells to develop into the specialized, unique cells needed to repair a patient’s defective or diseased bladder.

The breakthrough, developed at the UC Davis Institute for Regenerative Cures and published today (March 21) in the scientific journal Stem Cells Translational Medicine, is significant because it provides a pathway to regenerate replacement bladder tissue for patients whose bladders are too small or do not function properly, such as children with spina bifida and adults with spinal cord injuries or bladder cancer.

“Our goal is to use human stem cells to regenerate tissue in the lab that can be transplanted into patients to augment or replace their malfunctioning bladders,” said Eric Kurzrock, professor and chief of the division of pediatric urologic surgery at UC Davis Children’s Hospital and lead scientist of the study, which is titled “Induction of Human Embryonic and Induced Pluripotent Stem Cells into Urothelium.”

To develop the bladder cells, Kurzrock and his UC Davis colleagues investigated two categories of human stem cells. In their key experiments, they used induced pluripotent stem cells (iPS cells), which were derived from lab cultures of human skin cells and umbilical blood cells that had been genetically reprogrammed to convert to an embryonic stem cell-like state.

If additional research demonstrates that grafts of bladder tissue grown from human stem cells will be safe and effective for patient care, Kurzrock said that the source of the grafts would be iPS cells derived from a patient’s own skin or umbilical cord blood cells. This type of tissue would be optimal, he said, because it lowers the risk of immunological rejection that typifies most transplants.

In their investigation, Kurzrock and his colleagues developed a protocol to prod the pluripotent cells into becoming bladder cells. Their procedure was efficient and, most importantly, the cells proliferated over a long period of time – a critical element in any tissue engineering application.

“What’s exciting about this discovery is that it also opens up an array of opportunities using pluripotent cells,” said Jan Nolta, professor and director of the UC Davis Stem Cell program and a co-author on the new study. “When we can reliably direct and differentiate pluripotent stem cells, we have more options to develop new and effective regenerative medicine therapies. The protocols we used to create bladder tissue also provide insight into other types of tissue regeneration.”

Read more

For more health news, visit UC Health, subscribe by email or follow us on Flipboard.

CATEGORY: NewsComments Off

Grant supports research on the cause of childhood leukemia


UC Santa Cruz research could help enable the design of targeted cancer drugs.

Camilla Forsberg, UC Santa Cruz

Biomedical research at UC Santa Cruz has the potential to change how the most common type of childhood cancer is treated. A new grant from the nonprofit Alex’s Lemonade Stand Foundation will help UCSC researcher Camilla Forsberg advance her work to identify the root cause of acute lymphocytic leukemia (ALL) in infants and children.

Approximately 2,900 children and teens are diagnosed with ALL each year in the United States. Most are ages 2 to 3 years when diagnosed.

Forsberg, associate professor of biomolecular engineering in the Jack Baskin School of Engineering, and co-director for the UCSC Institute for the Biology of Stem Cells, is one of 16 researchers nationwide who have been awarded the foundation’s Innovations Awards. The two-year, $250,000 awards provide critical and significant seed funding for experienced investigators with novel and promising approaches to finding causes and cures for childhood cancers.

“Understanding the cause of this disease will enable the design of drugs that specifically eliminate cancer cells,” said Forsberg, “without causing damage to the body’s healthy cells while curing children with cancer.”

Avoiding treatment side effects is particularly important in children, as their growing bodies are much less able to tolerate standard chemotherapy. The idea of specific drug targeting is based on the success with the drug Gleevec in treating patients with chronic myelogenous leukemia.

Leukemia is a cancer that starts in early blood-forming cells. In a healthy child, the bone marrow makes blood stem cells (immature cells) that become mature blood cells over time. Cancer researchers like Forsberg are seeking a better understanding of what causes blood-forming stem cells to start behaving abnormally.

Read more

For more health news, visit UC Health, subscribe by email or follow us on Flipboard.

CATEGORY: NewsComments Off