Successful Transplant of Patient-Derived Stem Cells Into Mice With Muscular Dystrophy

Source: University College London
Date: 28 June 2012

Summary:

Stem cells from patients with a rare form of muscular dystrophy have been successfully transplanted into mice affected by the same form of dystrophy, according to a new study published today in Science Translational Medicine.

For the first time, scientists have turned muscular dystrophy patients’ fibroblast cells (common cells found in connective tissue) into stem cells and then differentiated them into muscle precursor cells. The muscle cells were then genetically modified and transplanted into mice. The new technique could be used in the future for treating patients with limb-girdle muscular dystrophy (a rare form in which the shoulders and hips are primarily affected) and, possibly, other forms of muscular dystrophies.

In this study, scientists focused on genetically modifying a type of cell called a mesoangioblast, which is derived from blood vessels and has been shown in previous studies to have potential in treating muscular dystrophy. However, the authors found that they could not get a sufficient number of mesoangioblasts from patients with limb-girdle muscular dystrophy because the muscles of the patients were depleted of these cells.

Instead, scientists in this study “reprogrammed” adult cells from patients with limb-girdle muscular dystrophy into stem cells and were able to induce them to differentiate into mesoangioblast-like cells. After these ‘progenitor’ cells were genetically corrected using a viral vector, they were injected into mice with muscular dystrophy, where they homed-in on damaged muscle fibres.

The researchers also showed that when the same muscle progenitor cells were derived from mice the transplanted cells strengthened damaged muscle and enabled the dystrophic mice to run for longer on a treadmill than dystrophic mice that did not receive the cells.

Scientists trigger muscle stem cells to divide

Source: Stanford University School of Medicine
Date: February 22, 2012

Summary:

A tiny piece of RNA plays a key role in determining when muscle stem cells from mice activate and start to divide, according to researchers at the Stanford University School of Medicine. The finding may help scientists learn how to prepare human muscle stem cells for use in therapies for conditions such as muscular dystrophy and aging by controlling their activation state.

It’s the first time that a small regulatory RNA, called a microRNA, has been implicated in the maintenance of the adult stem cell resting, or quiescent, state. The research is published Feb. 23 in Nature. Postdoctoral scholar Tom Cheung, PhD, is the first author of the study.

Researchers develop method of directing stem cells to increase bone formation and bone strength

Source: University of California - Davis
Date: February 6, 2012

Summary:

A research team led by UC Davis Health System scientists has developed a novel technique to enhance bone growth by using a molecule which, when injected into the bloodstream, directs the body's stem cells to travel to the surface of bones. Once these cells are guided to the bone surface by this molecule, the stem cells differentiate into bone-forming cells and synthesize proteins to enhance bone growth. The study, which was published online today in Nature Medicine, used a mouse model of osteoporosis to demonstrate a unique treatment approach that increases bone density and prevents bone loss associated with aging and estrogen deficiency.

A Shot of Young Stem Cells Made Rapidly Aging Mice Live Longer and Healthier, Pitt Team Says

Source: University of Pittsburgh School of Medicine
Date: January 3, 2012

Summary:

PITTSBURGH – Mice bred to age too quickly seemed to have sipped from the fountain of youth after scientists at the University of Pittsburgh School of Medicine injected them with stem cell-like progenitor cells derived from the muscle of young, healthy animals. Instead of becoming infirm and dying early as untreated mice did, animals that got the stem/progenitor cells improved their health and lived two to three times longer than expected, according to findings published in the Jan. 3 edition of Nature Communications.

ABC News, MSNBC, The Daily Mail and the Pittsburgh Tribune-Review carried news stories today on this development.

Research could help people with declining sense of smell

Source: University of California - Berkeley
Date: December 7, 2011

Summary:

University of California, Berkeley, neuroscientists have discovered a genetic trigger that makes the nose renew its smell sensors, providing hope for new therapies for people who have lost their sense of smell due to trauma or old age. The gene tells olfactory stem cells ‑ the adult tissue stem cells in the nose ‑ to mature into the sensory neurons that detect odors and relay that information to the brain. The discovery may also help scientists harness olfactory stem cells and stem cells found in other sensory systems more generally, to recover sensory function following injury or degenerative disease, scientists said. The findings are published in the Dec. 8 issue of the journal Neuron.

Cystic fibrosis-associated changes in lung stem cells may contribute to disease progression

Source: University of Iowa
Date: July 25, 2011

Summary:

Researchers at the University of Iowa's Roy J. and Lucille A. Carver College of Medicine have discovered that in cystic fibrosis (CF) patients, the airway glands are depleted of a specific population of airway stem cells that participate in airway repair following injury. Their results are published in the July 18 issue of Journal of Clinical Investigation.

First patients treated in new human embryonic stem cell study

Source: Washington Post
Posted: July 14, 2011 08:30 AM ET

Summary:

The Washington Post reports researchers have treated the first two patients in the second government-authorized attempt to evaluate a therapy created using human embryonic stem cells to treat Stargardt Macular Dystrophy, a progressive form of blindness:

Researchers have treated the first two patients in the second government-authorized attempt to evaluate a therapy created using human embryonic stem cells in the United States. A team led by Steven Schwartz at UCLA administered about 50,000 cells Tuesday into one eye of a volunteer suffering from Stargardt Macular Dystrophy, a progressive form of blindness that usually begins in childhood, and another with Dry Age-Related Macular Degeneration, the leading cause of blindness in the developed world, Advanced Cell Technology, which is sponsoring the study, announced Thursday.

ACT Announces First Patients Undergo Embryonic Stem Cell Transplantation Treatment for Stargardt's Disease and Macular Degeneration

Source: Advanced Cell Technology, Inc.
Date: July 14, 2011

Summary:

MARLBOROUGH, Mass. -- Advanced Cell Technology, Inc., a leader in the field of regenerative medicine, today announced the dosing of the first patients in each of its two Phase 1/2 clinical trials for Stargardt's macular dystrophy and dry age-related macular degeneration (dry AMD) using retinal pigment epithelial (RPE) cells derived from human embryonic stem cells (hESCs). The patients were treated Tuesday (July 12) by Steven Schwartz, M.D., Ahmanson Professor of Ophthalmology at the David Geffen School of Medicine at UCLA and retina division chief at UCLA's Jules Stein Eye Institute. Robert Lanza, M.D., chief scientific officer of ACT, attended the procedures. Both patients successfully underwent the outpatient transplantation surgeries and are recovering uneventfully.

Scientists Discover Switch To Speed Up Stem Cell Production To Facilitate Development Of Treatments For Diseases

Source: Agency for Science, Technology and Research (A*STAR)
Date: May 18, 2011

Summary:

A team of scientists from Genome Institute of Singapore (GIS) of the Agency for Science, Technology and Research (A*STAR) have shown how proteins involved in controlling genes work together to carry out their functions in stem cells and demonstrated for the very first time, how they can change interaction partners to make other types of cells. The work highlighted the collaborative nature of modern biology in which techniques and knowledge from bioinformatics analysis, structural biology, biochemistry and stem cell molecular biology were used together to find the specific amino acid within the protein that facilitated the molecular switch between stem cells and other types of cells. This discovery, published in the journal Stem Cells, has implications for generating stem cells more efficiently for biomedical applications and could help facilitate the development of treatments for diseases such as diabetes, Parkinson's disease, and Huntington's disease.

Study identifies stem cell-related changes that may contribute to age-related cognitive decline

Source: Cold Spring Harbor Laboratory
Date: May 5, 2011

Summary:

Cold Spring Harbor, N.Y. – A new study from Cold Spring Harbor Laboratory (CSHL) offers an explanation for why our brains produce fewer and fewer neurons with age, a phenomenon thought to underlie age-related cognitive decline. The study, published as the cover story in the May 6 issue of Cell Stem Cell, suggests that this drop in production is due to the shrinking cache of adult stem cells in our brains. The new neurons are critical for some facets of memory—for instance, when similar events need to be memorized as separate episodes—and for the response to anti-depressant therapies and repair after brain injury.

Uncovering the trail behind growing too old, too soon. Human model of rare genetic disease reveals new clues to ageing process

Source: Agency for Science, Technology and Research (A*STAR)
Date: January 24, 2011

Summary:

Scientists from A*STAR’s Institute of Medical Biology (IMB) in Singapore and the University of Hong Kong’s Department of Medicine have produced the world's first human cell model of progeria, a disease resulting in severe premature ageing in one in four to eight million children worldwide. This model has allowed them to make new discoveries concerning the mechanism by which progeria works. Their findings were published this month in the prestigious scientific journal, Cell Stem Cell [1].

Led by IMB’s Profs Alan Colman and Colin Stewart, the team used a novel technique of deriving induced pluripotent stem (iPS) cells from cells of human progeria patients[2]. This human progeria model allows the group to trace and analyse the distinctive characteristics of progeria as it progresses in human cells. Previously, only mouse models of the disease were available.

The researchers used their iPS cells to identify two types of cells - mesenchymal stem cells (MSCs) and vascular smooth muscle cells (VSMCs) – that were particularly adversely affected by progeria. This means that a young patient with progeria would typically have fewer MSCs and VSMCs than other children. MSCs were found to be very sensitive to a low oxygen environment and their losses could delay renewal of the various tissues they gave rise to, thus exacerbating the patient’s symptoms of ageing. The same effect on VSMCs could explain why their number was reduced in the patient’s heart vessels.

Advanced Cell Technology Receives FDA Clearance For Clinical Trials Using Embryonic Stem Cells to Treat Age-Related Macular Degeneration

Source: Advanced Cell Technology, Inc.
Date: January 3, 2011

Summary:

MARLBOROUGH, MA – Advanced Cell Technology, Inc., a leader in the field of regenerative medicine, announced today that the US Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application to treat Dry Age-Related Macular Degeneration (AMD) using retinal pigment epithelial (RPE) cells derived from human embryonic stem cells (hESCs). ACT is now permitted to initiate a Phase I/II multicenter clinical trial to treat patients with Dry AMD, the most common form of macular degeneration in the world. There are currently no treatments available for this prevalent disease of an aging global population. Dry AMD, representing a substantial global market opportunity and afflicts between 10-15 million Americans.

Medical News Today, The Los Angeles Times, Agence France Presse (AFP) and Bloomberg News carried news stories about the trial today.

Human Protein Improves Muscle Function of Muscular Dystrophy Mice

Source: Brown University
Date: December 27, 2010

Summary:

PROVIDENCE, R.I. [Brown University] — A novel potential therapy based on a natural human protein significantly slows muscle damage and improves function in mice who have the same genetic mutation as boys with the most common form of muscular dystrophy, according to a paper published online Dec. 27 in the Proceedings of the National Academy of Sciences.

Study of genetic disease reveals new path to cell reprogramming

Source: Harvard University
Date: November 21, 2010

Summary:

As debilitating as disease can be, sometimes it acts as a teacher. Researchers at Harvard Medical School and the Harvard School of Dental Medicine have found that by mimicking a rare genetic disorder in a dish they can rewind the internal clock of a mature cell and drive it back into an adult stem-cell stage. This new “stem cell” can then branch out into a variety of differentiated cell types, both in culture and in animal models. These findings appear online in Nature Medicine on Nov. 21.

Stem Cell Transplants in Mice Produce Lifelong Enhancement of Muscle Mass

Source: University of Colorado at Boulder
Date: November 10, 2010

Summary;

A University of Colorado at Boulder-led study shows that specific types of stem cells transplanted into the leg muscles of mice prevented the loss of muscle function and mass that normally occurs with aging, a finding with potential uses in treating humans with chronic, degenerative muscle diseases.

The experiments showed that when young host mice with limb muscle injuries were injected with muscle stem cells from young donor mice, the cells not only repaired the injury within days, they caused the treated muscle to double in mass and sustain itself through the lifetime of the transplanted mice. The study is published in the Nov. 10 issue of Science Translational Medicine.

News stories based on this news release were published in today's Daily Telegraph and Press Association.

Stem Cells Used to Treat Children With Life-Threatening, Blistering Skin Disease

Source: University of Minnesota
Date: August 12, 2010

Summary:

University of Minnesota Physician-researchers have demonstrated that a lethal skin disease can be successfully treated with stem cell therapy. Medical School researchers John E. Wagner, M.D., and Jakub Tolar, M.D., Ph.D., in collaboration with researchers in Portland, Oregon, the United Kingdom, and Japan have for the first time used stem cells from bone marrow to repair the skin of patients with a fatal skin disease called recessive dystrophic epidermolysis bullosa, or RDEB. This is the first time researchers have shown that bone marrow stem cells can home to the skin and upper gastrointestinal tract and alter the natural course of the disease. The results are published in the New England Journal of Medicine.

Below is a summary of media coverage of about this development:

Los Angeles Times, August 11, 2010, 1:59 p.m. PDT: "Stem cell therapy appears successful in treating rare, deadly skin disease":

Stem cell therapies hold enormous promise. But, so far, there are few confirmed stem cell treatments beyond traditional bone marrow transplantation. Researchers reported Wednesday, however, that they have been able to use stem cells to treat a rare, often-fatal skin disease in children. The results of the experimental therapy suggest that stem cells from bone marrow can travel to injured skin cells and repair damage to those cells.

Agence France Presse (AFP), August 11, 2010, 5:04 pm ET: "Doctors use bone marrow stem cells to treat skin disorder":

In what is believed to be a medical first, researchers have used stem cells from bone marrow to repair the skin of young patients with a painful and usually deadly skin disease, a study published Wednesday says. Researchers led by University of Minnesota doctors John Wagner and Jakub Tolar in 2007 began treating children with a rare genetic skin disorder, called recessive dystrophic epidermolysis bullosa (RDEB), with bone marrow stem cells that had been found in lab tests to repair skin in mice.

Reuters, August 11, 2010 5:27 pm EDT: "Stem cells may hold key for fatal skin disease":

High-risk bone marrow transplants partially cured five children with a potentially deadly genetic defect in which proteins that hold layers of skin together are absent, U.S. researchers said Wednesday. But one other child died from side effects of a drug used to prepare for a transplant and a second died from a post-transplant infection.

People with recessive dystrophic epidermolysis bullosa, or RDEB, are plagued by painful blisters on the skin, mouth and throat, caused by the slightest trauma that can expose the body to infection and, in some cases, an aggressive form of cancer. With the new treatment, "there was improved healing, fewer blisters, and their quality of life was positively affected. They could do things they couldn't do before, like ride a bicycle or go on a trampoline," said Dr. John Wagner of the University of Minnesota, who worked on the study.

It was published in the New England Journal of Medicine.

Minneapolis Star-Tribune, August 11, 2010 - 8:37 PM CDT: "U doctors find treatment for painful, lethal skin disease":

Two years ago, doctors at the University of Minnesota took an enormous risk by putting a little boy with a terrible skin disease through a bone marrow transplant. For that boy, Nate Liao, it worked out, and he is healthier now. Thursday, in a study published in the New England Journal of Medicine, the researchers are for the first time making public their results treating seven other children with the same genetic disease. In it, they acknowledge just how risky the procedure is: Two of the seven, including the older brother of the first patient, died as a result of the treatment. But in the others it worked -- a leap forward for a devastating and painful genetic disease for which there is no other treatment and a potentially significant advance for the use of adult stem cells.

HealthDay News, August 11, 2010: "Stem Cell Treatment May Offer Hope Against Fatal Skin Disorder":

A debilitating and usually fatal skin disorder may be treated by bone marrow stem cell transplant, a new study finds. The results may have implications for the treatment of other skin diseases and also for the potential of stem cells in bone marrow to turn into other cell types, according to the study published in the Aug. 12 issue of the New England Journal of Medicine.

Stanford Develops New Method To Grow Adult Stem Cells

Source: KGO AM 810 - San Francisco, CA
Date: July 15, 2010

Stanford researchers have come up with a better petri dish. KGO's Jenna Lane explains it's a special surface for growing stem cells.

Scientists develop new way to grow adult stem cells in culture

Source: Stanford University Medical Center
Date: July 15, 2010

Summary:

STANFORD, Calif. — Researchers at the Stanford University School of Medicine have developed a technique they believe will help scientists overcome a major hurdle to the use of adult stem cells for treating muscular dystrophy and other muscle-wasting disorders that accompany aging or disease: They've found that growing muscle stem cells on a specially developed synthetic matrix that mimics the elasticity of real muscle allows them to maintain their self-renewing properties.

Adult stem cells already exist in the body, and are important in regenerating tissues like blood, muscles and neurons in the brain. But scientists have struggled to produce them in quantities needed for therapies because the cells differentiate and lose their "stemness" as soon as they're placed in a tissue culture dish. This new method of growing the cells creates a way to study the behavior of many types of adult stem cells in culture and may revolutionize the ability to produce these cells for future therapies, say the researchers. The research will be published online July 15 in Science Express.

Mechanism that may trigger degenerative disease identified

Source: Penn State University
Date: June 25, 2010

Summary:

A mechanism that regulates stem-cell differentiation in mice testes suggests a similar process that may trigger degenerative disease in humans, according to researchers at Penn State University. Research involved manipulating a protein called STAT3 that signals stem cells to decide whether to differentiate into a specialized type of cell or self-renew and remain stem cells. By manipulating STAT3, researchers identified a key regulator of spermatogonial stem cell self-renewal. Every time a stem cell divides, it produces two new cells. The findings were published in the June online issue of Biology of Reproduction.

Researchers create retina from human embryonic stem cells

Source: University of California - Irvine
Date: May 26, 2010

Summary:

UC Irvine scientists have created an eight-layer, early stage retina from human embryonic stem cells, the first three-dimensional tissue structure to be made from stem cells. It also marks the first step toward the development of transplant-ready retinas to treat eye disorders such as retinitis pigmentosa and macular degeneration that affect millions.

In the study, researchers utilized the differentiation technique to create the multiple cell types necessary for the retina. The greatest challenge, Keirstead said, was in the engineering. To mimic early stage retinal development, the researchers needed to build microscopic gradients for solutions in which to bathe the stem cells to initiate specific differentiation paths. The UCI researchers are testing the early-stage retinas in animal models to learn how much they improve vision. Positive results would lead to human clinical trials.

The study appears online in the Journal of Neuroscience Methods.