The role of endothelial cells in myofiber differentiation and the vascularization and innervation of bioengineered muscle tissue in vivo.
Musculoskeletal disorders are a major cause of disability and effective treatments are currently lacking. Tissue engineering affords the possibility of new therapies utilizing cells and biomaterials for the recovery of muscle volume and function. A major consideration in skeletal muscle engineering is the integration of a functional vasculature within the regenerating tissue. In this study we employed fluorescent cell labels to track the location and differentiation of co-cultured cells in vivo and in vitro. We first utilized a co-culture of fluorescently labeled endothelial cells (ECs) and muscle progenitor cells (MPCs) to investigate the ability of ECs to enhance muscle tissue formation and vascularization in an in vivo model of bioengineered muscle. Scaffolds that had been seeded with both MPCs and ECs showed significantly greater vascularization, tissue formation and enhanced innervation as compared to scaffolds seeded with MPCs alone. Subsequently, we performed in vitro experiments using a 3-cell type system (ECs, MPCs, and pericytes (PCs)) to demonstrate the utility of fluorescent cell labeling for monitoring cell growth and differentiation. The growth and differentiation of individual cell types was determined using live cell fluorescent microscopy demonstrating the utility of fluorescent labels to monitor tissue organization in real time.
Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Tracy L
TL
Criswell
Benjamin T
BT
Corona
Zhan
Z
Wang
Yu
Y
Zhou
Guoguang
G
Niu
Yong
Y
Xu
George J
GJ
Christ
Shay
S
Soker
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D020007:Implants, Experimental; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000187:drug effects; D009132:Muscles / Q000098:blood supply* / Q000187:drug effects / Q000294:innervation*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D034421:Sus scrofa; D023822:Tissue Engineering / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A