Biomedical Engineering Reference
In-Depth Information
Focus of Stem Cell Research and Its Implication upon
Neurological Stem Cell Therapy: Mapping the Molecular
Scenario in Order to Engineer Repaired Brain Tissue
In order to be able to understand how to optimize the use of stem cells in clinical
arena and brain tissue engineering scientists focused their research to the funda-
mentals—e.g., the chain of molecular events that regulate the decision of adult
stem cells to perpetuate self-renewal or differentiate into more defined and/or
mature cells.
Signaling Pathways that Maintain Stem Cells
in an Undifferentiated State
The ability to maintain mammalian tissues throughout adult life depends on the
persistence of stem cells. They are maintained in numerous adult tissues by self-
renewal (dividing to make more stem cells), raising the question of whether this
process is regulated by mechanisms that are conserved between tissues. A growing
evidence that stem cells gone awry in their efforts to repair tissue damage could help
explain why long-term irritation, such as from alcohol or heartburn, can create a
breeding ground for certain cancers. It is too early to jump into generalization, but
accumulated data could be summarized as follows:
Hedgehog and Wnt stem-cell repair mechanism
Two key chemical signals, called Hedgehog and Wnt (“wint”) that are active in
the stem cells that repair damaged tissue, have also recently and unexpectedly
been found in certain hard-to-treat cancers, supporting an old idea that some
cancers may start from normal stem cells that have somehow gone bad. Normal
stem-cell self-renewal is a tightly regulated process, so the question is how and
whether such regulation is circumvented in cancer.
Wnt
The place to start looking is the activity and regulation of Hedgehog and Wnt,
which are best known for their roles in embryonic development, because recent
studies show that they are key regulators of self-renewal in at least some of the
body's normal tissue stem cells and are active in numerous cancer types ( 22- 24 ) .
If these stem cells are the starting point of some cancers, multiple genetic and
other changes may be required to trap the stem cell during chronic irritation, and
perhaps many more changes to get the rapid growth of cancer. We need to figure
out what those changes might be. Hedgehog activity has been found in certain
cancers of the lung, brain, stomach, esophagus, skin, pancreas, bladder, muscle,
and prostate ( 24 ). Similarly, Wnt activity has been tied to certain cancers of the
colon, liver, blood, bone, and lung. In experiments at Hopkins and elsewhere,
blocking Hedgehog and Wnt in laboratory-grown cancer cells and in animals has
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