Biomedical Engineering Reference
In-Depth Information
sphere-forming cells [42], but their interrelations are not totally
clear. Because of their cardiomyogenic potential, transplanted
cardiac stem/progenitor cells are expected eventually to replace a
damaged/lost myocardium. Indeed, it has already been reported
that cardiac stem/progenitor cells, injected directly into the heart
tissue, differentiated into cardiomyocytes [37, 42]. We prepared
sheets of Sca-1-positive cardiac progenitor cells (CPCs) derived from
murine hearts by using culture dishes coated with a temperature-
responsive polymer and tested them for transplantation in a murine
model of myocardial infarction [43]. Results showed significantly
greater improvement in left ventricular systolic performance
four weeks after transplantation in mice that received CPC sheets
compared to control mice (no transplantation) and showed that
the number of cardiomyocytes differentiated from CPC sheets was
sufficient to replace approximately 5% of cardiomyocytes in a
murine heart. However, amelioration of cardiac dysfunction cannot
be explained solely by these findings. Since increases in capillary
density and suppression of fibrosis were confirmed in damaged sites
after transplantation of CPCs, the involvement of factors produced
by the transplanted cells was suggested. Comprehensive analysis
by cytokine antibody array revealed that the culture supernatants
of CPCs contained significantly higher levels of sVCAM-1 than those
of control cells. Also, sVCAM-1 expression remained high in mice
that had received CPCs but not in control mice. Furthermore, the
culture supernatants of CPCs were shown to have angiogenic effects,
suppress cardiomyocyte death, and promote migration of the CPCs
themselves in vivo. When expression of the sVCAM-1 receptor
a
b
1
integrin was suppressed after transplantation of the CPC sheets,
the effects of transplantation, including improvement in cardiac
function, enhanced angiogenesis, and suppression of fibrosis, were
diminished and the engraftment of CPCs was suppressed. Taken
together, it is considered that transplantation of CPCs improves
cardiac function in a complex manner, promoting angiogenesis,
suppressing fibrosis, protecting cardiomyocytes, and promoting cell
migration and survival. Recently, multiple groups have reported that
human CPCs secrete proteins such as VEGF, HGF, IGF-1, and TIMP-1
[44, 45]. VEGF and HGF are most likely to play a role in angiogenesis.
It was reported that HGF and IGF-1 injected directly into the border
zone of myocardial infarct promoted migration, proliferation, and
differentiation of endogenous cardiac stem cells [46], suggesting
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