Stem Cell Research

Skin Cells Turned Into Neural Precusors, Bypassing Stem Cell Stage

New research has converted mouse skin cells directly into cells that become the three main parts of the nervous system. The finding is an extension of a previous study (post)  by the same group showing that mouse and human skin cells can be directly converted into functional neurons.

Importantly, the multiple successes of the direct conversion method could refute the idea that pluripotency is necessary for a cell to transform from one cell type to another. Together, the results raise the possibility that embryonic stem cell research and another technique called “induced pluripotency” could be supplanted by a more direct way of generating specific types of cells for therapy or research.

This new research is a substantial advance over the previous work in that it transforms the skin cells into neural precursor cells as opposed to neurons. While neural precursor cells can differentiate into neurons they can also become the two other main cell types in the nervous system: astrocytes and oligodendrocytes.

Therapeutically Useful Stem Cell Derivatives Need Stability

New research suggests that neural derivatives of human pluripotent stem cells frequently acquire extra material from chromosome 1q, a chromosomal defect that has been associated with some blood cell cancers and pediatric brain tumors with poor clinical outcomes. 

The good news is that the same researchers found that the abnormal neural cells detected were unable to form tumors in mice.  The new cautionary data however does suggests the necessity of additional quality controls to ensure that neural derivatives of human pluripotent stem cells are not genomically unstable, a common characteristic of cancer cells.  The research was accomplished by Natalie Lefort and colleagues, at the Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, France.

In commentary concerning the research, Neil Harrison, at the University of Sheffield, United Kingdom, noted that while the data raise safety issues relevant for the therapeutic use of these cells, the fact that the same chromosome was affected in all cases suggests that it should be possible to design screening strategies to detect and remove these cells.

Adapted from the Institute for Stem Cell therapy and Exploration of Monogenic Diseases announcement.

 

Researchers Find First Step In Strategy For Parkinson's Disease Induced Pluripotent Stem Cell Replacement Therapy

Induced pluripotent stem cells (iPSC) are a promising avenue for cell replacement therapy in neurologic diseases. For example, mouse and human iPSCs have been used to generate dopaminergic (DA) neurons that improve symptoms in rat Parkinson's disease models.

Now researchers have evaluated the growth, differentiation, and function of human-derived iPSC-derived neural progenitor cells (NPCs) in a primate model, and have elucidated their therapeutic potential.

"We developed a series of methods to induce human iPSCs to become NPCs, using a feeder-free culture method, and grafted NPCs at different stages of differentiation into the brain of a monkey PD* model," said Jun Takahashi, MD, PhD, of Kyoto University. "We developed a method to evaluate the growth and DA activity of the grafts using magnetic resonance imaging (MRI), positron emission tomography (PET), immunocytochemistry, and behavioral analyses, all of which will be useful in preclinical research."

Video: Irving Weisman On The Importance Of The Distinction Between Embryonic And Adult Stem Cells

The ethical argument concerning the use of embryonic stem cells continues to rage and may well be an issue in the upcoming 2012 election. The use of embryonic stem cells in research is continually questioned in some quarters on the premise that the growing success of adult stem cell research makes embryonic stem cell research unnecessary. In this four minute video Dr. Weissman explains what it's like to work with one type of cell versus the other and why the research distinction is important.

Irving Weissman is one of the older generation of stem cell pioneers.  He is a professor of pathology and developmental biology and the director of Stanford University School of Medicine's Institute of Stem Cell Biology and Regenerative Medicine.

 

In 1988, Dr. Weissman became the first to isolate in pure form any stem cell in any species when he isolated the hematopoietic or blood-forming stem cell in mice. He subsequently isolated the human hematopoietic stem cell, the human neuronal stem cell, and the human leukemia stem cell. 
Dr. Weissman's research encompasses the phylogeny and developmental biology of the cells that make up the blood-forming and immune systems.

Stem Cells Show Promise In Delivering Gene Therapy For Hunington's Disease

In a promising approach that might block the disease from advancing, researchers have developed a technique for using stem cells to deliver therapy that specifically targets the genetic abnormality found in Huntington's disease. Huntington's disease can be managed with medications, but currently there are no treatments for the physical, mental and behavioral decline of its victims.

"We have been able to successfully deliver inhibitory RNA sequences from stem cells directly into neurons, significantly decreasing the synthesis of the abnormal huntingtin protein," said Jan A. Nolta, Director of the UC Davis stem cell program and the UC Davis Institute for Regenerative Cures.

Human Pluripotent Stem Cells Induced To Become High Purity Vascular Smooth Muscle

Using human pluripotent stem cells, researchers have discovered a method for creating high purity vascular smooth muscle. 

Although blood and cardiac cells from human pluripotent stem cells have been created before, this is the first time that all the major types of vascular smooth muscle cells have been developed in an easily scalable manner.

In the UK, one in three of all deaths is due to cardiovascular disease. The vast majority of these are caused by atherosclerosis, a ‘furring up’ and blockage of blood vessels. For patients who are unsuitable for conventional stenting or bypass treatment, one option in the future may be to grow new blood vessels to bypass their own blocked vessels.

Video: Lawrence Goldstein -- Evidence-based Development of Stem Cell Therapies

As we move forward in clinical trials for autologous and allogeneic stem cell therapies, recognition of what we don't know and what we do is both critical and constantly changing. The integration of this expanding stem cell knowledge with the parallel expansion of our knowledge of the biochemestry and molecular biology of the human body will hopefully produce continually improving therapies. However, the acquisition of knowledge and understanding is not linear. Research in therapies can get ahead of our understanding of disease process and have. This video is a reality check on what we know of neurodegenerative disease and potential therapy as of October 2011. It is well worth watching.

Taking place at the World Stem Cell Summit, this talk is about 37 minutes long. With an emphasis on Alzheimer's disease, Dr. Goldstein does a truly excellent job of pointing out the difficulty of understanding

Factor That Translates Mechanical Work In Muscles Into Chemical Growth Signal To Muscle Stem Cells Found

We take it for granted, but the fact that our muscles grow when we work them makes them rather unique. Turns out a factor produced in working muscle fibers apparently tells surrounding muscle stem cells that it's time to multiply. In other words, this serum response factor (Srf) translates the mechanical signal of work into a chemical one.

"This signal from the muscle fiber controls stem cell behavior and participation in muscle growth," says Athanassia Sotiropoulos of Inserm in France. "It is unexpected and quite interesting."

New Research Sheds Light On Early Embryonic Stem Cell Development Through First Time Birth Of Chimeric Monkeys From Stem Cells Taken From Two Separate Embryos

Conducted to gain a better understanding of the differences between natural stem cells residing in early embryos and their cultured embryonic stem cell  counterparts, the new work also determined that stem cell functions and abilities differ between primates and rodents.

The first cels studied were those that were totipotent – cells from the early embryo that have the ability to divide and produce all of the differentiated cells in the placenta and the body of an organism. These were compared with pluripotent cells – cells derived from the later stage embryo that have the ability to produce all body parts except those necessary for reproduction.

Flexible Neural Stem Cells Found In A Single Layer At The Back Of The Human Eye

That cell layer, known as the retinal pigment epithelium (RPE), underlies and supports photoreceptors in the light-sensitive retina. Without it, photoreceptors and vision are lost. The new study shows that the RPE also harbors self-renewing stem cells that can wake up to produce actively growing cultures when placed under the right conditions. They can also be coaxed into forming other cell types.

"You can get these cells from a 99-year-old," said Dr. Sally Temple, co-founder and scientific director of the Neural Stem Cell Institute in Rensselaer, New York. "These cells are laid down in the embryo and can remain dormant for 100 years. Yet you can pull them out and put them in culture and they begin dividing. It is kind of mind boggling."

Intervention With Young Stem Cells Makes Aging Mice Live Longer And Healthier

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. Previous research has revealed stem cell dysfunction, such as poor replication and differentiation, in a variety of tissues in old age, but it's not been clear whether that loss of function contributed to the aging process or was a result of it (see previous post).

Tissue Degeneration Found In Aging Is Partially Caused By Mitochondrial Dysfunction In Stem Cells

Research models have preciously found that an accumulation of mitochondrial genome defects leads to symptoms of premature aging: thin skin, graying of hair, baldness, osteoporosis and anemia.

In a breakthrough revealing the unexpected importance of energy metabolism in regulating stem cell function and tissue maintenance, new research on the mechanisms of age-associated degeneration indicates that tissue degeneration can be caused by mitochondrial dysfunction in tissue stem cells. Stem cell function may be modified with the result that progeny cells in blood and the nervous system are dysfunctional.