Biomedical Engineering Reference
In-Depth Information
Role of Stem Cells in Repair of the Heart
Role of Stem Cells in Cardiac Regeneration Following Injury
The ability to regenerate damaged heart tissue is present in all vertebrate species
but, for unknown reasons, humans and other mammals have “turned off” this regen-
eration function. Although multiple types of progenitor (undifferentiated stem)
cells have been identified within the mammalian heart, it displays little or no regen-
eration when damaged. In contrast, when a portion of a zebrafish's heart is removed,
it regenerates and activation of Notch signaling pathway precedes the regeneration.
A new study shows that regeneration proceeds through two coordinated stages fol-
lowing resection of the ventricular apex of the zebrafish heart: (1) a blastema is
formed, comprising of progenitor cells that express precardiac markers, undergo
differentiation, and proliferate; and (2) tissue surrounding both cardiac chambers
induces developmental markers and rapidly expands, creating a new epithelial
cover for the exposed myocardium (Lepilina et al.
2006
). A subpopulation of these
epicardial cells undergoes epithelial-to-mesenchymal transition, invades the wound,
and provides new vasculature to regenerating muscle. During regeneration, the
ligand fgf17b is induced in myocardium, while receptors fgfr2 and fgfr4 are
induced in adjacent epicardial-derived cells. When FGF signaling is experimentally
blocked by expression of a dominant-negative Fgf receptor, neovascularization
fails, prematurely arresting regeneration. These findings reveal injury responses by
myocardial and epicardial tissues that collaborate in an FGF-dependent manner to
achieve cardiac regeneration. Future studies in zebrafish could help us discover
why this regenerative ability is lacking in mammals and potential ways to stimulate
it. Discovering the key to this dormant ability could lead to new ways to treat
human hearts damaged by disease.
Cardiomyocytes Derived from Adult Skin Cells
In 2010, Prof. Robert Schwartz of the University of Houston, Texas, devised a
method for converting ordinary human skin cells into heart cells. Although adult
skin cells have been converted into stem cells previously, this method requires
fewer steps. The cells developed are similar to ESCs and ultimately can be made
into early stage heart cells derived from a patient's own skin. These then could be
implanted and grown into fully developed functioning heart cells, reversing the
damage caused by previous heart attacks. These new cells would replace the dam-
aged cardiac tissue that weakens the heart's ability to pump, develops into scar
tissue, and causes arrhythmias. Early clinical trials using these reprogrammed cells
on actual heart patients are planned. It may be possible to grow an entirely new
heart or other organ from these reprogrammed cells.
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