Biomedical Engineering Reference
In-Depth Information
Mesenchymal stem cells express proteins involved in ECM synthesis,
such as collagens, MMP, serine proteases, and serine protease
inhibitors [23], and suppress the proliferation of cardiac fibroblasts
and collagen synthesis [24]. Transplantation of these cells reverted
elevated expression of collagen type I, collagen type III, TIMP-1, and
TGF
in a rat model of myocardial infraction [25], suggesting that
transplanted mesenchymal stem cells contribute to suppression
of cardiac remodeling in an injured heart by directly regulating
the expression of ECM proteins in the host heart. In addition,
transplanted mesenchymal stem cells appear not to trigger host
immune responses, and allogenically transplanted cells survive in
the host without immunosuppressants [26], indicating their anti-
inflammatory effects. Onishi et al. reported that transplantation
of mesenchymal stem cells resulted in improvement of cardiac
function, accompanied by suppression of increases in CD68-positive
inflammatory cells and expression of MCP-1 in a rat model of acute
myocarditis [27].
b
2a.5
Skeletal Myoblasts
Skeletal myoblasts are considered to have therapeutic potential
because they can be prepared from the host sources to allow
autologous transplantation, they are ischemia resistant, and they
are able to differentiate into nonmyocytes. Skeletal myoblasts do not
differentiate into cardiomyocytes in vivo [28] and cannot support
the myocardium for synchronous contraction, because connexin
activity, which enables electrical coupling with surrounding
cardiomyocytes, is absent in these cells. On the other hand, several
studies have provided evidence that transplantation of these cells
suppresses fibrosis and apoptosis and promotes angiogenesis,
thereby ameliorating cardiac dysfunction caused by ischemic
and nonischemic insult [29-31] and indicating the importance
of paracrine effects. Various angiogenic factors such as VEGF,
placental growth factor (PIGF), angiogenin, angiopoietin, HGF, and
PDGF-BB, as well as antifibrotic factors such as MMP2, MMP9, and
MMP10, have been found in the supernatants of human skeletal
myoblast culture [32], suggesting the involvement of these factors
in myocardial repair. The Myoblast Autologous Grafting in Ischemic
Cardiomyopathy (MAGIC) trial, which investigated cases of depressed
