The present study tested the hypotheses that i) transforming growth
factor beta 1 (TGF-β1) enhances differentiation of rat bone marrow mesenchymal stem
cells (MSCs) towards the cardiomyogenic phenotype and ii)
intramyocardial implantation of the TGF-β1-treated MSCs improves cardiac function in
heart failure rats. MSCs were treated with different concentrations of TGF-β1 for 72
h, and then morphological characteristics, surface antigens and mRNA expression of
several transcription factors were assessed. Intramyocardial implantation of these
TGF-β1-treated MSCs to infarcted heart was also investigated. MSCs were initially
spindle-shaped with irregular processes. On day 28 after TGF-β1 treatment, MSCs
showed fusiform shape, orientating parallel with one another, and were connected with
adjoining cells forming myotube-like structures. Immunofluorescence revealed the
expression of cardiomyocyte-specific proteins, α-sarcomeric actin and troponin T, in
these cells. The mRNA expression of GATA4 and
Nkx2.5 genes was slightly increased on day 7, enhanced on day 14
and decreased on day 28 while α-MHC gene was not expressed on day 7,
but expressed slightly on day 14 and enhanced on day 28. Transmission electron
microscopy showed that the induced cells had myofilaments, z line-like substances,
desmosomes, and gap junctions, in contrast with control cells. Furthermore,
intramyocardial implantation of TGF-β1-treated MSCs to infarcted heart reduced scar
area and increased the number of muscle cells. This structure regeneration was
concomitant with the improvement of cardiac function, evidenced by decreased left
ventricular end-diastolic pressure, increased left ventricular systolic pressure and
increased maximal positive pressure development rate. Taken together, these results
indicate that intramyocardial implantation of differentiated MSCs enhanced by TGF-β1
improved cardiac function in heart failure rats.
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