Using Adult, Embryonic Stem Cells For Tissue Regeneration: New Advances
ScienceDaily (Nov. 17, 2008) - A major issue in the development of
regenerative medicine is the cell sources used to rebuild damaged tissues.
In a review of the issue published in Developmental Dynamics, researchers
state that inducing regeneration in humans from the body's own tissues by
chemical means is feasible, though many questions must be answered before
the process can reach clinical status.
Regeneration is a regulative developmental process ubiquitous across all
species. It functions throughout the life cycle to maintain or restore the
normal form and function of cells, tissues and, in some cases organs,
appendages and whole organisms. The roots, stems and leaves of plants, for
example, have extensive regenerative capacity, and entire plants can grow
from single cells or small cuttings.
The regenerative capability of most vertebrate animals, however, is
restricted to certain tissues. In the absence of injury, many cell types
such as epithelia and blood cells turn over rapidly, while others such as
hepatocytes, myofibers, osteocytes, and most neurons, have low turnover
rates or do not turn over at all. In organisms that grow throughout life,
such as fish, the total number of cells in various tissues increases
continuously, indicating that the number of new cells produced is higher
than the number of cells lost.
By contrast, the loss of normal tissue mass and/or architecture to acute
injury or disease in humans requires a more intense and qualitatively
different regenerative response that restores the tissue to its original
state. This response is called injury-induced regeneration.
A major issue for cell transplant therapies is the source of the cells to be
used. Three sources of cells can be tapped for transplant: differentiated
tissues, adult stem cells (ASCs) and derivatives of embryonic stem cells
(ESCs). Adult stem cells regenerate epithelia, brain tissue, muscle, blood
and bone. They have also been found in other tissues that normally scar
after injury, such as myocardium, spinal cord and retina tissues.
"Adult stem cell therapy has real potential to regenerate at least muscle
and bone damaged by injury or genetic disease, and cardiac stem cells may be
a way to regenerate new cardiomyocytes after myocardial infarction," says
David L. Stocum, co-author of the paper.
Progress is also being made toward the use of ESCs to derive functional
cells for treatment of diabetes and muscular dystrophy.
A procedure has been developed to direct the differentiation of human ESCs
to pancreatic islet cells, including insulin producing cells. When implanted
into mice, the cells produce human insulin in response to glucose
stimulation and protect against hyperglycemia.
"ESCs show great promise as a cell source for the regeneration of new
tissue, due to their high growth and self-renewal capacity, and their
ability to differentiate into a myriad of precursor or differentiated cell
types when directed by the appropriate set of environmental factors," says
co-author Günther K.H. Zupanc.
The recently acquired ability to reprogram adult somatic cells to ESCs in
culture ("induced pluripotent stem cells") has solved bioethical concerns
surrounding the destruction of somatic cell nuclear transfer embryos to make
personal embryonic stem cells that will not be immunorejected. The authors
state, however, that induced pluripotent stem cells raise their own
biological and bioethical issues. Biological issues include the
differentiation and survival time of reprogrammed somatic cells, and the
need to develop methods to reprogram cells without introducing exogenous
DNA. Ethical issues, including cost, the ease of reprogramming for the
purpose of conducting unethical experiments, like the derivation of human
offspring, have yet to be resolved.
The ability to reprogram adult somatic cells to ESCs in culture has led the
authors to the concept that it may be possible to use natural or synthetic
molecules to reprogram adult somatic cells in vivo to adult stem cells that
will recapitulate the development of a tissue, organ or appendage, or to
stimulate resident adult stem cells to do so. They argue that strong
regenerators, such as fish and amphibians know how to do this naturally, and
should be studied to learn what molecules are required for such stimulation
or reprogramming. The counterparts of these molecules, or synthetic small
molecules that mimic their action, could then be applied to
regeneration-deficient mammalian tissues.
Adapted from materials provided by Wiley-Blackwell, via EurekAlert!, a
service of AAAS.
Wiley-Blackwell (2008, November 17). Using Adult, Embryonic Stem Cells For
Tissue Regeneration: New Advances. ScienceDaily. Retrieved November 17,
2008, from http://www.sciencedaily.com /releases/2008/11/081106164816.htm
Rayilyn Brown
Director AZNPF
Arizona Chapter National Parkinson Foundation
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