Construction of a unidirectionally beating 3-dimensional cardiac muscle construct.
BACKGROUND
Cardiac tissue engineering aims to construct cardiac tissue with characteristics similar to those of the native tissue. Engineered cardiac tissues (ECTs) can be constructed using synthetic scaffold or liquid collagen. We report an initial study using our own newly designed cardiac muscle device to construct heart tissue. We investigated the effects of cell seeding density and collagen quantity on the formation of liquid collagen-based cardiac muscle.


METHODS
We obtained cardiac myocytes from neonatal rats mixed with collagen type I and matrix factors cast in circular molds to form circular strands. Cell densities (0.1 x 10(7) to 6 x 10(7)) and collagen quantity (0.3 to 1.0 ml/ECT) were tested. Cell gross morphology, cell orientation, spatial distribution and ultrastructure were evaluated using histologic analyses, confocal laser scanning microscopy and transmission electron microscopy.


RESULTS
Histologic analyses of ECTs revealed that cardiac cells reconstituted longitudinally oriented, cardiac bundles with morphologic features characteristic of the native tissue. Confocal and electron microscopy demonstrated that, using optimized cell density and collagen quantity, we made ECTs with characteristic features similar to those of native differentiated myocardium.


CONCLUSIONS
ECTs comparable to native cardiac tissue can be engineered under optimized conditions. This construct is a first step in the development of cardiac tissue engineered in vitro, and may be used as a basis for studies of cardiac development, drug testing and tissue replacement therapy.
Zhao
Yun-Shan
YS
Beijing Institute of Basic Medical Sciences, Beijing, PR China.
Wang
Chang-Yong
CY
Li
De-Xue
DX
Zhang
Xi-Zheng
XZ
Qiao
Yue
Y
Guo
Xi-Min
XM
Wang
Xiu-Li
XL
Dun
Cui-Mi
CM
Dong
Ling-Zhi
LZ
Song
Ying
Y
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D005260:Female; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D023421:Models, Animal; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology* / Q000637:transplantation / Q000648:ultrastructure*; D051381:Rats; D017208:Rats, Wistar; D012518:Sarcomeres / Q000648:ultrastructure; D012680:Sensitivity and Specificity; D023822:Tissue Engineering / Q000379:methods*