OBJECTIVE: We previously showed that
autologous myoblast sheets constructed with tissue-engineering techniques improved the function of the
impaired heart. In this study, we evaluated the effects of layered
myoblast sheets to clarify whether increasing the number of sheets provides improvement of
cardiac function. METHODS:
Myoblast sheets were constructed in dishes that release confluent cells from the dish surface via temperature reduction. Sixty
infarcted Lewis rats underwent
implantation of
myoblast sheets on the
infarcted area. There were 4 groups (n = 15 in each group): S1: one layer, S3: three layers, S5: five layers, and a sham group. We examined
cardiac function by
echocardiography and catheterization,
mRNA expression by real time
reverse-transcriptase polymerase chain reaction, and
histology. RESULTS: The
ejection fraction and end-systolic pressure-volume relationship in the S5 and S3 groups were significantly improved. End-diastolic area was significantly reduced in the S5 group. The
mRNAs for
hepatocyte growth factor,
vascular endothelial growth factor, and stromal cell-derived factor-1 were all up-regulated in dose-dependent fashion. On
histologic examination,
fibrosis was most decreased in S5, and vascular
density was increased. Cellular
hypertrophy was
attenuated in both the S5 and S3 groups.
Elastic fibers were massively up-regulated in the
infarction and implanted sheets in the S5 and S3 groups, with expression of the
elastin gene. CONCLUSIONS:
Implantation of three- and five-layered
myoblast sheets yields favorable results, with better improvement of
cardiac function, induction of
angiogenesis, more
elastic fibers, and less
fibrosis. Thus, layered
myoblast sheets, in optimal numbers, may
attenuate adverse
cardiac remodeling of the
infarcted heart.
