New advancements in the use of adult, embryonic stem cells for tissue regenerati

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New advancements in the use of adult, embryonic stem cells for tissue

regeneration

http://www.eurekalert.org/pub_releases/2008-11/w-nai110608.php

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 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.