Biomedical Engineering Reference
In-Depth Information
infarcted myocardium, and gene therapies using these cytokines
have already been used clinically for treating heart failure [26-30].
On the other hand, because the combination of HGF and VEGF
leads to better engraftment and angiogenesis compared to either
factor alone [31], the transplantation of cells that produce various
cytokines should be of great advantage in therapies for ischemic
tissues because of enhanced tissue survival and neovascularization.
Because SDF-1 is a ligand for CXC chemokine receptor 4 (CXCR4), the
chemokine recruits CXCR4-positive hematopoietic stem cells and
endothelial progenitor cells (EPCs) and also induces angiogenesis in
vivo via the recruitment of endothelial cells (ECs), which up-regulate
CXCR4 expression after VEGF stimulation [32-34]. It has been
confirmed that the SkM sheet patch transplantation provides much
better therapeutic effects than the needle injection of dissociated
cells. Sekiya et al. have clarified that implantation of a quintuple-
layered SkM sheet patch improved cardiac function, up-regulated
the messenger ribonucleic acids (mRNAs) for HGF and SDF-1, and
decreased fibrosis compared to transplantation of a single-layer
sheet [35]. In addition, elastic fibers are massively up-regulated in the
infarction and implanted cell sheets in the layered cell sheet group,
with expression of the elastin gene. Elastic fibers are important
in the elasticity and resilient recoil of tissues and maintenance of
the integrity of tissue architecture against repeated expansion [36,
37]. In fact, the transplantation of elastin gene-transfected cells
attenuates negative cardiac remodeling of the infarcted myocardium
of rat models [38]. Hoashi et al. have demonstrated, using the rat
model of a pressure-overloaded right ventricle, that SkM sheet patch
transplantation improved right-heart failure as well as left-heart
failure [39].
In a preclinical trial, Miyagawa et al. have performed experiments
using a chronic infarcted porcine model [40]. They confirm that
SkM sheet transplantation onto an infarcted myocardium improves
cardiac function by attenuating negative cardiac remodeling in
the ischemic myocardium. The improvement of cardiac function
is maintained for at least six months, and well-developed smooth
muscle cells are observed in the transplanted area. On the basis of
these results, clinical trials of autologous SkM sheet transplantation
in heart failure patients are now underway. A patient who was
suffering from dilated cardiomyopathy received autologous SkM
sheet patch transplantation [41]. From an approximately 10 g
piece of the skeletal muscle of the patient, SkMs were grown to
