Biomedical Engineering Reference
In-Depth Information
proliferation and secretion of suitable matrix. The proliferated cells com-
municate and specialize to form different types of cells, each for specifi c
function, using their secreted matrix to help in their function and commu-
nication. In wound healing, the body tries to mimic what happens during
normal development. It attempts to replace the damaged tissues taking
advantage of the temporary extracellular matrix consisting of fi brin-
fi bronectin meshwork which is formed during the fi rst hemorrhagic phase.
This matrix facilitates migration of different cell types that proliferate to
regenerate or repair the defect. The initial infl ammatory reaction helps in
the healing process through its mediators which attract appropriate cells
that perceive and correctly respond to the matrix signals.
6.4
The Paradigm Shift in Tissue Engineering:
Biomimetic Approaches to Stimulate Endogenous
Repair and Regeneration
6.4.1
Harnessing Endogenous Repair via Mesenchymal
Stem Cells
Mesenchymal stem cells have long been defi ned by their self-renewal
and multipotential differentiation properties. The growing consensus is
that mesenchymal stem cells and pericytes sharing a panel of common
markers are actually one and the same [66]. The present theory is that
pericytes are released from broken or infl amed blood vessels at the site
of tissue damage to become mesenchymal stem cells (MSC). The latter
are then activated by the injury releasing a myriad of bioactive molecules
which fi rst modulate the immune response and then secrete trophic fac-
tors thereby creating a regenerative microenvironment [67].
In light of recent evidence from MSC therapy studies for cardiovas-
cular disease it seems unlikely that they directly contribute to replen-
ishing differentiated cell populations. Indeed, MSC engraftment in the
heart has been shown to be quite low as is their transdifferentiation post-
transplantation into cardiomyocytes [68]. This has led to the belief that
the positive role of MSC is rather via immunomodulatory and remodeling
effects. Bone marrow-derived MSC can secrete trophic factors that induce
activation and proliferation of cardiac progenitor cells thus mediating
cardiovascular regeneration. This will probably lead to next generation
MSC-based therapeutics that exploit the MSC secretome. Analysis of the
in vitro secreting profi le of MSC has since shown that they secrete a vari-
ety of cytokines that are anti-apoptotic, immunosuppressive, proliferation
enhancing, and angiogenesis modulating [69].
Bone marrow derived stromal cells (BMC) have also been shown to stim-
ulate arteriogenesis through paracrine mechanisms [70]. Evidence shows
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