Biomedical Engineering Reference
In-Depth Information
fabricated and that their characteristics were similar to those of native tissues. Transplanta‐
tion of these cell sheets induced corneal surface reconstruction in rabbits. For patients who
suffer from unilateral limbal stem deficiency, corneal epithelial cell sheets can be cultured
from autologous limbal stem cells. When the objective is to repair the bilateral corneal stem
cell deficiency, autologous oral mucosal epithelial cells are utilized to create oral mucosal
epithelial cell sheets. The cell sheets contain both cell-to-cell junctions and extracellular ma‐
trix proteins, and can be transplanted without the use of any carrier substrates or sutures.
Therefore, oral mucosal epithelial sheets were examined as an alternative cell source to ex‐
pand the possibilities of autologous transplantation. Autologous transplantation to rabbit
corneal surfaces successfully reconstructed the corneal surface and restored transparency.
Four weeks after the transplantation, epithelial stratification was similar to that of normal
corneal epithelia, although the keratin expression profile retained characteristics of the oral
mucosal epithelium.
2.2.2. Cardiac regeneration
To enhance the function of cardiac tissue, neonatal rat cardiomyocyte sheets were fabricated
and examined (Shimizu et al., 2002). When 4 sheets were layered, spontaneous beating of
the engineered constructs was observed. When they were transplanted subcutaneously,
heart tissue-like structures and neovascularization within the contractile tissues were ob‐
served. The long-term survival of pulsatile cardiac grafts was confirmed for more than one
year in rats (Shimizu et al., 2006a). Another study was performed to create thick tissue in
rats (Shimizu et al., 2006b). However, the thickness limit for the layered cell sheets of subcu‐
taneous tissue was ~80 µm (3 layers). To overcome this limitation, several transplantations
of triple-layer grafts were performed, resulting in an approximately 1 mm-thick myocardi‐
um with a well-organized microvascular network. Other types of cell sheets were also exam‐
ined to improve cardiac function. Adipose-derived mesenchymal stem cells in mice
(Miyahara et al., 2006) and skeletal myoblasts in dogs, rats, and hamsters (Hata et al., 2006;
Hoashi et al., 2009; Kondoh et al., 2006) were transplanted as cell sheets, demonstrating the
efficacy of the method for cardiac repair.
2.2.3. Cartilage regeneration
Chondrocyte sheets applicable to cartilage regeneration were prepared using cell sheet man‐
ufacturing technique that takes advantage of temperature responsive culture dishes. The
layered chondrocyte sheets were able to maintain the phenotype of cartilage and could be
attached to sites that exhibited cartilage damage. The cell sheets act as a barrier for prevent‐
ing the loss of proteoglycan from these sites and for protection against catabolic factors in
the joints of rabbits (Kaneshiro et al., 2006).
2.2.4. Esophageal regeneration
With the recent development of endoscopic submucosal dissection (ESD), large esophageal
cancers can be removed using a single procedure. However, complications, such as postop‐
erative inflammation and stenosis, frequently occur after an aggressive ESD procedure,
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