TY - JOUR
T1 - Engineering vascularized skeletal muscle tissue
AU - Levenberg, Shulamit
AU - Rouwkema, Jeroen
AU - Macdonald, Mara
AU - Garfein, Evan S.
AU - Kohane, Daniel S.
AU - Darland, Diane C.
AU - Marini, Robert
AU - Van Blitterswijk, Clemens A.
AU - Mulligan, Richard C.
AU - D'Amore, Patricia A.
AU - Langer, Robert
N1 - Funding Information:
The authors thank the MIT division of comparative medicine for excellent assistance in tissue embedding and processing, Adam Kapur for help with data analysis, and Justin S. Golub for help with RT-PCR assays. We would like to thank Joseph Itskovitz-Eldor for assistance and cooperation in conducting this research. This work was supported by National Institutes of Health grants HL60435 (R.L. and S.L.) and EY05318 (P.A.D. and D.C.D.).
PY - 2005
Y1 - 2005
N2 - One of the major obstacles in engineering thick, complex tissues such as muscle is the need to vascularize the tissue in vitro. Vascularization in vitro could maintain cell viability during tissue growth, induce structural organization and promote vascularization upon implantation. Here we describe the induction of endothelial vessel networks in engineered skeletal muscle tissue constructs using a three-dimensional multiculture system consisting of myoblasts, embryonic fibroblasts and endothelial cells coseeded on highly porous, biodegradable polymer scaffolds. Analysis of the conditions for induction and stabilization of the vessels in vitro showed that addition of embryonic fibroblasts increased the levels of vascular endothelial growth factor expression in the construct and promoted formation and stabilization of the endothelial vessels. We studied the survival and vascularization of the engineered muscle implants in vivo in three different models. Prevascularization improved the vascularization, blood perfusion and survival of the muscle tissue constructs after transplantation.
AB - One of the major obstacles in engineering thick, complex tissues such as muscle is the need to vascularize the tissue in vitro. Vascularization in vitro could maintain cell viability during tissue growth, induce structural organization and promote vascularization upon implantation. Here we describe the induction of endothelial vessel networks in engineered skeletal muscle tissue constructs using a three-dimensional multiculture system consisting of myoblasts, embryonic fibroblasts and endothelial cells coseeded on highly porous, biodegradable polymer scaffolds. Analysis of the conditions for induction and stabilization of the vessels in vitro showed that addition of embryonic fibroblasts increased the levels of vascular endothelial growth factor expression in the construct and promoted formation and stabilization of the endothelial vessels. We studied the survival and vascularization of the engineered muscle implants in vivo in three different models. Prevascularization improved the vascularization, blood perfusion and survival of the muscle tissue constructs after transplantation.
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U2 - 10.1038/nbt1109
DO - 10.1038/nbt1109
M3 - Article
C2 - 15965465
AN - SCOPUS:24944477341
SN - 1087-0156
VL - 23
SP - 879
EP - 884
JO - Nature biotechnology
JF - Nature biotechnology
IS - 7
ER -