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Engineering vascularized skeletal muscle tissue
Shulamit Levenberg1, Jeroen Rouwkema, Mara Macdonald
1Department of Biomedical Engineering, Technion 32000, Haifa, Israel. shulamit@bm.technion.ac.il
Nature Biotechnology
|June 21, 2005
Summary
Engineering thick muscle tissue requires in vitro vascularization. This study shows that adding embryonic fibroblasts to engineered muscle constructs promotes blood vessel network formation, improving tissue survival after transplantation.
Area of Science:
- Tissue Engineering
- Regenerative Medicine
- Vascular Biology
Background:
- Engineering thick, complex tissues like muscle faces challenges in achieving adequate in vitro vascularization.
- In vitro vascularization is crucial for cell viability, structural organization, and successful implantation of engineered tissues.
- Developing methods for prevascularization can enhance the integration and function of engineered muscle constructs.
Purpose of the Study:
- To induce and stabilize endothelial vessel networks within engineered skeletal muscle tissue constructs in vitro.
- To investigate the role of embryonic fibroblasts in promoting vascularization within engineered muscle.
- To evaluate the survival and vascularization of prevascularized engineered muscle implants in vivo.
Main Methods:
- Utilized a three-dimensional multiculture system with myoblasts, embryonic fibroblasts, and endothelial cells on biodegradable polymer scaffolds.
- Analyzed conditions for vessel induction and stabilization, focusing on the impact of embryonic fibroblasts and vascular endothelial growth factor (VEGF) expression.
- Assessed the survival and vascularization of engineered muscle implants in three different in vivo models post-transplantation.
Main Results:
- Engineered skeletal muscle constructs successfully formed endothelial vessel networks.
- The addition of embryonic fibroblasts significantly increased vascular endothelial growth factor expression, promoting vessel formation and stabilization.
- Prevascularization of engineered muscle constructs led to improved vascularization, blood perfusion, and enhanced survival of the muscle tissue after transplantation in vivo.
Conclusions:
- A three-dimensional multiculture system with specific cell types and scaffolds can induce functional vascular networks in engineered muscle.
- Embryonic fibroblasts play a key role in promoting vascularization through increased VEGF expression.
- In vitro prevascularization is a viable strategy to improve the in vivo performance and survival of engineered skeletal muscle tissue.