“9.61x6.69” b2815 Tissue Engineering and NanotheranosticsEngineering Approaches for Creating Skeletal Muscle 93.3. Mesenchymal Stem Cells
The MSCs are resident stem cells in many tissues of the body, and are
best known for their ability to differentiate into osteogenic, adipo-
genic, and chondrogenic lineages.^32 Several criteria for the identifica-
tion of MSCs have been identified by the International Society for
Cellular Therapy.^33 These criteria include adherence to plastic during
culture and the ability to differentiate into osteoblasts, adipocytes,
and chondrocytes.^33 In addition, the cells must be CD105, CD73 and
CD90 positive but CD45, CD34, CD14 or CD11b, CD79alpha,
CD19 and HLA-DR negative.^33 More recently, MSCs have been
shown to support muscle cell growth, and can differentiate and fuse
to form multinucleated myofibers.^34 There is increasing evidence that
MSCs are involved in the upkeep of various tissues, especially through
the release of growth factors and regulation of the behavior of mono-
potent tissue stem cells.^35 MSCs are also known to play a role in
modulating the immune response through various mechanisms
including contact inhibition of T-cells and B-cells.^39 During angio-
genesis, MSCs act as pericytes, playing a significant role in stabilizing
the stalks of new vessels.^40 They can be easily isolated from bone and
adipose tissue, and expand easily in vitro. All of these aspects make
these cells attractive for tissue engineering of skeletal muscle, espe-
cially since immunogenicity and lack of vascularization are issues that
continue to plague the field. Recent attempts to utilize MSCs for
restoring muscle tissue have shown great promise, although the
descriptions for the mechanism of healing varies between some tests
that find MSCs directly contributing to the myofiber population, and
other tests that show MSCs only seeming to support growth through
secretion of growth factors.^41 Although MSCs can differentiate into
myoblast lineages in vitro, doubt has been casted on the ability of the
in vivo environment to also induce such a change.^42 In vitro differen-
tiation of MSCs can be accomplished through growth in media
designed for skeletal muscle or culture media conditioned by skeletal
muscle cells.^43 While these techniques have been shown to cause
differentiation, more work is needed to fully replicate the adult
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