Biomedical Engineering Reference
In-Depth Information
8
3 × 10
cells for three weeks. Circular SkM sheet patches (thickness:
approximately 50 µm; diameter: 40 mm) were fabricated. Quadruple-
layered SkM sheets were transplanted on 5 sites for a total of 20 cell
sheets. The patient has been in good clinical condition and has shown
(1) improvement of cardiac function (ejection fraction: increased
from 26% [8 weeks after cell sheet transplantation] to 46% [at 3
months]); (2) a gradual decline of the patient's brain natriuretic
peptide levels, reaching a plateau after transplantation; (3)
discontinuation of a left ventricular-assist system; (4) no necessity
of cardiac transplantation; and (5) no symptoms of arrhythmia.
5b.3.2
Mesenchymal Stem Cell Sheet Patch
MSCs are present in adult tissues, including the bone marrow
and adipose tissue. They can also be isolated and propagated as
easily as SkMs, so there have been numerous clinical trials using
MSCs around the world. However, recently a meta-analysis of the
treatment of myocardial infarction with bone marrow stem cells
shows a small improvement in the left ventricular ejection fraction
in needle-based injection [5]. Miyahara
et al. have revealed that
the MSC sheet transplantation (1) reversed wall thinning in the
scar area, (2) improved cardiac function, and (3) prolonged animal
survival in a rat myocardial infarction model [42]. MSC sheets
also produce large amounts of angiogenesis-related cytokines
(VEGF and HGF) similar to SkM sheets, and interestingly, in vivo a
single-layer MSC sheet transplanted onto the myocardium induces
the formation of numerous new blood vessels and the tissue
thickens (to approximately 600 µm). On the other hand, in vivo
only few MSCs differentiate into cardiomyocytes. Hida et al.
have
demonstrated in vivo cardiac repair using a menstrual blood-
derived mesenchymal cell (MMCs) sheet created on fibrin polymer-
coated culture dishes [43]. Importantly, MMCs can differentiate
into beating cardiomyocytes by cocultivating with mouse cardiac
cells. MMCs exhibit a cardiomyocyte-specific action potential, and
cardiomyocytes account for approximately 30% of the MMCs in
vitro. In an in vivo study, engrafted MMCs are transdifferentiated
into cardiomyocytes within the myocardial infarction area, which
might contribute to an improvement in cardiac function.
