Biomedical Engineering Reference
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to have a high potential to repair hearts in younger patients with
congenital defects.
6b.3.4
Comparison between Dissociated Cell Injection
and Cell Sheet Transplantation
Dissociated cardiac cells have been injected into the left dorsal
subcutaneous tissue of nude rats, and layered cardiac cell sheets
have been transplanted into the right dorsal subcutaneous tissue
of the same rats, and the sites of dissociated cell injection and cell
sheet transplantation are analyzed histologically and compared
[42]. A bump is formed under the skin in the case of cell injection,
whereas the cell sheet transplanted site is smooth. A cross-sectional
view of the cell-injected graft site shows a cell-dense graft surface
zone with cell-void central necrotic areas, which is a typical image
found in high-density cell implants. Terminal deoxynucleotidyl
transferase (TdT)-mediated 2´-deoxyuridine, 5´-triphosphate
(dUTP)-biotin nick-end labeling (TUNEL)-positive cells are also
detected within the injected graft. An eosinophilic cytoplasm, nuclei
deformation, and neutrophils are also detected in the necrotic tissue
in the injected cell graft site. By contrast, TUNEL-positive cells
are hardly detected in the transplanted cardiac cell sheet at any
period after transplantation. Many GJs are detected within the cell
sheet in contrast to few depositions within the cell injection site.
In vivo bioluminescence measurement also shows that cardiac cell
sheet transplantation consistently yields greater cell survival than
dissociated cell injection [54]. These results clarify the advantage of
cell sheet transplantation over dissociated cell injection.
6b.4
Therapeutic Effect of Cardiac Cell Sheet
Transplantation on Cardiovascular Disease
Three-dimensional myocardial tissue fabricated by layering cardiac
cell sheets can be easily transplanted onto a damaged heart without
suture. The transplantation of layered cardiac cell sheets onto
an infarcted rat heart induces the establishment of electrical and
functional connections between cardiac cells within implanted cell
sheets and the host heart via functional GJ formation [55]. In addition,
the transplantation of layered cardiac cell sheets provides functional
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