Provocative New Theory Redefines Concept of Stem Cells and How They Work, According to Editor of Leading Journal, Stem Cells and Development
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[Source: Source: Mary Ann Liebert, Inc.]
Tuesday September 6, 3:35 pm ET
NEW ROCHELLE, N.Y.--(BUSINESS WIRE)--Sept. 6, 2005--Stem cells, both embryonic and adult, may not, as previously believed, regenerate damaged tissues simply by producing youthful, multipotent cells, but may instead have a more complex, poorly understood function that calls into question the way they provide therapeutic utility, according to an editorial in the August 2005 issue (Volume 14, Number 4) of Stem Cells and Development, a peer-reviewed journal published by Mary Ann Liebert, Inc. (www.liebertpub.com). The editorial is available free online at www.liebertpub.com/scd.
Recent reports from credible investigators must be addressed as they "bring into question the potential utility of stem cell therapy, both embryonic and adult," writes journal Editor-in-Chief, Denis English, Ph.D., Professor of Neurosurgery and Director of Cell Biology of the Center of Excellence for Aging and Brain Repair Research of the University of South Florida College of Medicine in Tampa. Dr. English notes that stem cells show therapeutic promise for heart, brain and pulmonary disease, but asserts that recent studies from Indiana University, Stanford, and other centers bring into question the issue of "transdifferentiation," wherein one cell differentiates into a different cell. The concept of transdifferentiation, now besieged, has long been held out as the fundamental hypothesis at the basis of the therapeutic promise of stems cells. Reports that transdifferentiation does not occur call into question the promise of stem cell therapy. These reports must be taken seriously and cannot readily be dismissed, according to Dr. English. "Therefore they must be addressed," he says.
Dr. English notes that stem cell therapy indeed is promising. "Differentiation of stem cells appears to be more complex than first thought and involves both the limitation as well as the activation of new protein expression," he asserts. If these therapeutic results do not result from transdifferentiation, or "plasticity," then the stem cells must act in a manner that has not been previously recognized. Reports in Stem Cells and Development suggest another theory, which contends that instead of an individual stem cell giving rise to new tissues, a more complex "stem system" may be needed for tissue repair and regeneration.
Further questioning the accepted function of stem cells is a paper by George Plopper, Ph.D. and colleagues from the esteemed Rensselaer Polytechnic Institute. Dr. Plopper's data show that the differentiation of stem cells into other functional cell types depends on the inhibition or decrease in expression levels, rather than the addition of newly expressed proteins, as had been widely thought.
At least two consequences are apparent from these reports, according to Dr. English. Most reports of the failure of stem cells to transdifferentiate are based on the absence of finding new proteins in regenerated tissue. Dr. Plopper's report suggests that stem cell differentiation involves focusing of protein expression rather than expansion of expression. If this is the case, absence of observation of new protein expression is not evidence for the absence of differentiation. Dr. Plopper's state of the art manuscript shows that stem cells express more proteins than their progeny, and other reports demonstrate that excess proteins can inhibit the ability of cells to differentiate. Thus, in contrast to what was previously thought, stem cell differentiation apparently involves limitations of protein expression rather than the expression of new proteins, bestowing upon the cells derived from stem cells new functional and morphological properties.
An alternative hypothesis is put forth by Dr. Paul Sanberg and colleagues in the October issue of the journal. This group holds that stem cells protect neural damage by stopping the cascade of events that lead to progressive brain and spinal cord disease after the initial injury. Dr. Sanberg and associates propose that stem cells exert their effects not by regenerating new neural tissue, but by dampening the inflammatory response; a response that can certainly impede healing. In the August issue of the journal, investigators from Dr. Sanberg's group show for the first time the amelioration of pathology of chronic brain disease by stem cell therapy and attribute the protective effects of cord blood derived stem cells to inhibition of the inflammatory response.
Stem Cells and Development is an authoritative peer-reviewed journal published bimonthly in print and online. The Journal is dedicated to communication and objective analysis of developments in the biology, characteristics, and therapeutic utility of stem cells. A complete table of contents and free sample issue may be viewed online at www.liebertpub.com/scd.
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