Stem Cell Research

Gladstone And Stanford To Develop Induced Pluripotent Stem (IPS) Cells For Cardiac Stem Cell Treatments

Researchers from the Gladstone Institute of Cardiovascular Disease (GICD), led by Director Deepak Srivastava, MD, will collaborate with a Stanford research team led by Robert Robbins, MD, professor and chair of cardiothoracic surgery, to investigate the use of induced pluripotent stem cells (iPS cells) to repair damaged heart muscle. The research consortium will be funded by the National Heart, Lung and Blood Institute (NHLBI).

iPS cells result from the “reprogramming” of adult cells into cells closely resembling embryonic stem cells. Like ESCs, they can develop into any cell type in the body. This technology was developed by Gladstone investigator Shinya Yamanaka, MD, PhD. the 2009 Lasker Award Recipient for Biomedical Research.

"Important gaps remain in our understanding of stem and progenitor cells," said NHLBI director Elizabeth Nabel, MD. "This consortium holds great promise to expand our knowledge and uncover therapeutic applications of great public impact.”

Neural Stem Cells In Mice Affected By Gene Associated With Longevity

A gene associated with longevity in roundworms and humans has been shown to affect the function of stem cells that generate new neurons in the adult brain.  The study suggests the gene may play an important role in maintaining cognitive function during aging.

Unlike skin or intestine, the adult human brain doesn’t make a lot of new cells. But those it does are critical to learning, memory and spatial awareness. To meet these demands, the brain maintains two small caches of neural stem cells. In each cache, stem cells can self-renew and give rise to neurons and other cells known as oligodendrocytes and astrocytes. Properly balancing these functions allows the generation of new nerve cells as needed while also maintaining a robust neural stem cell pool.

“It’s intriguing to think that genes that regulate life span in invertebrates may have evolved to control stem cell pools in mammals,” said Anne Brunet, PhD, assistant professor of genetics at the Stanford University School of Medicine.

As mice and other organisms age, the pool of neural stem cells in the brain shrinks and fewer new neurons are generated. These natural changes correlate with the gradual loss of cognitive ability and sensory functions that occur as we approach the end of our lives. However, the life span of some laboratory animals can be artificially extended by mutating genes involved in metabolism, and some humans outlive their life expectancy (about 70 years for someone born in 1960) by decades. Brunet and her colleagues wanted to know why.

Small Molecule Platform For Commercial-Scale Reprogramming Announced

Fate Therapeutics, Inc. claims to have significantly improved the speed and efficiency of reprogramming adult cells into human induced-pluripotent stem cells (iPSCs) using a combination of small molecules.

The discovery, which was made by Sheng Ding, Ph.D. under a research collaboration between Fate Therapeutics and The Scripps Research Institute (TSRI), represents a more than 200-fold improvement in reprogramming efficiency and reduces the reprogramming period to two weeks as compared to methods using only the four reprogramming factors (Oct 3/4, Sox2, Klf4 and c-Myc).

This advancement has implications for the creation of "pharmaceutical grade" iPSCs, reprogrammed cells that can be produced without genetic modification at commercial scale quantity, quality and consistency.

Harvest Technologies, Thermogenesis, Cytori Therapeutics: Stem Cell Extraction, Processing And The FDA

Harvest Technologies is a private company now competing head to head with our Publicly Traded Sector Company, Thermogenesis (KOOL).  We say 'now' because, while Harvest has been in the bone marrow stem cell point of care harvesting and processing business for some time, Thermogenesis now has an entry in this market as well.

What these three companies have in common is this: Each subscribes to the notion that point of care processing and delivery of autologous stem cells and related growth factors will be superior to existing approaches and to alternative stem cell treatment solutions for certain therapeutic applications.  Each company is supporting one or more clinical tests that use the particular company's stem cell processing device, an approach that feeds the implication that a therapeutic result is tied directly to the use of the device. 

China And California Announce Collaboration To Advance Stem Cell Research toward Stem Cell Therapy

In a step taken to broaden the potential pool of expertise that can be applied toward research in a specific area, a new agreement between the California Institute for Regenerative Medicine (CIRM) and the Chinese Ministry of Science and Technology (MOST) will make it easier for researchers in both California and China to obtain joint stem cell research funding. 

Researchers in both jurisdictions will be invited to form teams that will apply jointly for funding through a process that builds upon routine CIRM and MOST procedures. For those that are approved, CIRM will fund the California researchers and MOST will fund the Chinese researchers.

“One of CIRM’s primary goals is to accelerate the field of stem cell research as a whole, and in some instances we can do this more effectively through collaborations that involve the best scientific endeavors, regardless of geography,” said Alan Trounson, President of CIRM. “China is developing a major national program in stem cells and regenerative medicine that can be effectively matched with California’s excellence in stem cell science that is rapidly evolving in academic and biotechnology settings. I would expect major developments for patients to occur through this new partnership.”

Study Gains New Insight Into Stem Cell Regenerative Process And Organism Death

Stem Cell Regenerative Medicine is the controlled differentiation of stem cells into the functionally defined cells required to mend or replace sick or damaged tissue or organs.  Our bodies do this naturally, generating rather than regenerating a complete body from a single cell, growing and maintaining the body during our early years, maintaining it during adulthood, and then somehow allowing the process to deteriorate as the body ages and finally dies.

Shedding some new light on the process of aging and death, It turns out that the loss of two proteins,  the tumor-suppressor protein p53 and the DNA-maintenance protein ATR, results in tissues deteriorating rapidly generally resulting in death.

Essentially, argued senior author Eric Brown, PhD, Assistant Professor of Cancer Biology at the University of Pennsylvania School of Medicine, the findings highlight the fact that day-to-day maintenance required to keep proliferative tissues like skin and intestines functional is about more than just regeneration, the stem cell-based process that forms the basis of tissue renewal. It's also about housekeeping, the clearing away of damaged cells.

Harvard Stem Cell Research Team Reports Major Step In Producing Induced Pluripotent Stem Cells

Finding a way to produce safe iPS cells that are the biological equivalent of embryonic stem cells is especially important because the cells can then be created from the cells of individual patients for transplantation into those patients. Once accomplished, a patient with Parkinson’s disease might be treated with neurons created from his own cells, theoretically eliminating the need for immunosuppressive drugs, or the possibility of rejection of the transplanted cells. Similarly, patient-specific iPS cells could be used to create muscle for damaged hearts, or other individualized treatments.

A team of Harvard Stem Cell Institute (HSCI) researchers has made a major advance toward producing induced pluripotent stem cells, or iPS cells, that are safe enough to use in treating diseases in patients.

“We’re halfway home, and remarkably we got halfway home with just one chemical,” said Kevin Eggan, a Harvard Stem Cell Institute principal faculty member who is the senior author of this study.

Bioengineered 'Patch' Formed To Create Heart Stem Cell Treatment

In addition to combining appropriatly selected stem cells with necessary growth factors, one of the problems in coming up with stem cell treatments has been the necessity of providing a 'structure,' or 'scaffold' to give cells and growth factors a framework that fools them into thinking they're in a natural environment for growth.  This is particularly true where organ regeneration is concerned.  While generally in the very early stages, organ regeneration remains the holy grail of stem cell research.  A fair amount of the initial effort in this regard, both by academic labs and both private and publicly traded stem cell companies, has been directed to regenerating portions of the heart, in particular that damaged by scar tissue.

To that end, Duke University bioengineers have created a novel mold of unique design to fashion a three-dimensional "patch" made up of heart muscle cells, known as cardiomyocytes. The new tissue grown in the mold exhibited the two most important attributes of heart muscle cells -– the ability to contract and the ability to conduct electrical impulses. The mold looks much like a piece of Chex cereal in which researchers varied the shape and length of the pores to control the direction and orientation of the growing cells.

As a result, Duke bioengineers believe they have taken an important first step toward growing a living "heart patch" to repair heart tissue damaged by disease.

NHLBI Awards $170 Million To Create The Progenitor Cell Biology Consortium And Fund Related Stem Cell Research

The National Heart, Lung, and Blood Institute (NHLBI), one of the National Institutes of Health, has awarded $170 million to be paid over seven years to 18 teams of research scientists to develop the high-potential field of stem and progenitor cell tools and therapies.

The awards create the NHLBI Progenitor Cell Biology Consortium, which will bring together researchers from the heart, lung, blood, and technology research fields. A seven-year project, the consortium assembles nine research hubs with multidisciplinary teams of principal investigators and an administrative coordinating center to focus on progenitor cell biology.

“This is a grand experiment,” said Irving Weissman, MD, director of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine. “By forming this consortium, the NHLBI is encouraging a dialogue between scientific groups that would otherwise be competing with one another. I am very excited, and have high hopes that this will accelerate the understanding of stem and progenitor cells to the point of medical therapies.”

Umbilical Cord Blood Found To Be Ready Source For Off-The-Shelf, Patient-Specific, Induced Pluripotent Stem cells

Umbilical cord blood cells can successfully be reprogrammed to function like embryonic stem cells, thus setting the basis for a comprehensive bank of tissue-matched, cord blood-derived induced pluripotent stem (iPS) cells for off-the-shelf applications.

Worldwide, there are already more than 400,000 cord blood units banked along with immunological information. Cells found in umbilical cord blood contain a minimal number of cell mutations and possess the immunological immaturity of newborn cells, allowing the HLA donor-recipient match to be less than perfect without the risk of immune rejection of the transplant.

Human leukocyte antigen (HLA) typing is used to match patients and donors for bone marrow or cord blood transplants. HLAs are special surface markers found on most cells in the body and help the immune system to distinguish between "self" and "non-self." Selecting common HLA haplotypes from among already banked cord blood units to create iPS cell would significantly reduce the number of cell lines needed to provide a HLA match for a large percentage of the population.

Since the first adult cells were converted into iPS cells, they have generated a lot excitement as an uncontroversial alternative to embryonic stem cells and as a potential source for patient-specific stem cells. Unfortunately, taking a patient's cells back in time is not only costly, but could be difficult when those cells are needed right away to mend injured spinal cords or treat acute diseases, and outright impossible when the effects of aging or chronic disease have irrevocably damaged the pool of somatic cells.

Researchers Turn Back Clock On Old Human Muscle, Restoring Its Ability To Repair And Rebuild Itself

Previous research in animal models has revealed that the ability of adult stem cells to do their job of repairing and replacing damaged tissue is governed by the molecular signals they get from surrounding muscle tissue.  It has also suggested that those signals change with age in ways that preclude productive tissue repair.

Prior studies have also shown that the regenerative function in old stem cells can be revived given the appropriate biochemical signals.  What was not clear until this study was whether similar rules applied for humans.  Unlike humans, laboratory animals are bred to have identical genes and are raised in similar environments. Moreover, the typical human lifespan lasts seven to eight decades, while lab mice are reaching the end of their lives by age 2.

In a new study lead by Professor Irina Conboy, faculty member in the graduate bioengineering program at the University of California, Berkeley, researchers have identified critical biochemical pathways linked to the aging of human muscle. By manipulating these pathways, they were able to turn back the clock on old human muscle, restoring its ability to repair and rebuild itself.

"Our study shows that the ability of old human muscle to be maintained and repaired by muscle stem cells can be restored to youthful vigor given the right mix of biochemical signals," said Conboy.  "This provides promising new targets for forestalling the debilitating muscle atrophy that accompanies aging, and perhaps other tissue degenerative disorders as well."

Stem Cell Treatments To Create Replacement Cartilage Grow Closer To Reality

Following up on previous research at Hopkins described below, Jennifer Elisseeff Phd, speaking this week at the 2009 World Stem Cell Summit in Baltimore, described how she and her colleagues have guided stem cells to patch up patients' damaged and deteriorating knee cartilage.

"And their function is better," she said. "They might not be star athletes, but they can go out and do something like playing doubles tennis," which their injuries had made impossible before treatment.

The hydrogel is placed in the injured cartilage in a honey-like consistency, solidified with ultraviolet light, and attached to the tissue with a "glue" the lab developed. The porous material absorbs the blood and marrow and stem cells released from micro-fractures, guiding it into the shape needed to fill the hole and providing a fertile place to grow.

In a few months, the gel degrades, leaving -- if things work out -- new cartilage formed by the stem cells.

In their first clinical trial, conducted in Europe to take advantage of lower costs and easier regulatory hurdles, Elisseeff's team treated 15 adults who had at least a two-year history of knee cartilage injuries.

One year after treatment, the cartilage defects were still 89 percent filled on average, compared with the 50 percent expected with traditional treatments. And based on ratings of pain reduction and restored function, treatments using the new biogels and stem cells did twice as well as those getting micro-fracture treatments alone.