Biomedical Engineering Reference
In-Depth Information
the electrical cell-cell connections within the cardiac cell sheet are
completely conserved even just after detachment. The mild cell
recovery method by only a temperature decrease can preserve
(1) ion channels, which are closely related to the generation of
cardiomyocyte-action potentials, on cardiomyocytes within the
cardiac cell sheet and (2) functional cell-cell junction including
gap junctions (GJs), which are essential for electrical couplings
between cardiomyocytes, among cardiomyocytes within the cell
sheet. An electrical coupling of two cardiac cell sheets is rapidly
established at approximately 40 min after layering via functional
GJ formation. Connexin 43 (Cx43) is detected on a nonoverlapping
cell membrane as well as at cell-cell interfaces within a detached
cardiac cell sheet. The preservation of Cx43, which is thought to be a
GJ precursor, on the nonoverlapping cell membrane must be related
to rapid GJ formation between layered cardiac cell sheets, because
GJs are formed by only docking of two GJ precursors without the
transcription of Cx43 ribonucleic acids (RNAs), the translation
and maturation of Cx43 proteins, vesicular transport, etc. [44]. In
addition, a deposited ECM on a cardiac cell sheet may also promote
the intimate attachment between layered cell sheets and accelerate
the docking of GJ precursors. Preservation of GJ precursors and the
ECM on a cardiac cell sheet is recognized to be important in the rapid
and complete electrical coupling of layered cell sheets. Scaffold-free
cell sheet engineering has advantages in the rapid formation of GJs
and electrical coupling within 3D myocardial tissue. Thus, electrically
communicative 3D myocardial tissue can be easily fabricated by
layering cardiac cell sheets, and the fabricated 3D myocardial tissue
beats spontaneously, synchronously, and macroscopically [45].
6b.3
In vivo Transplantation of Layered Cardiac
Cell Sheets
6b.3.1
Rapid Neovascularization after Cardiac Cell Sheet
Transplantation
Layered cardiac cell sheets can be easily and reproductively adhered
to host tissues without suture [42, 45, 46]. When a layered cardiac
cell sheet is transplanted into the subcutaneous tissue of athymic
rats, at day 1 after the transplantation, numerous erythrocyte
