title: The effect of in vitro formation of acetylcholine receptor (AChR) clusters in engineered muscle fibers on subsequent innervation of constructs in vivo.
abstract: Timely innervation of muscle tissue is critical in the recovery of function, and this time-sensitive process relies heavily on the host tissue microenvironment after implantation. However, restoration of muscle tissue mass and function has been a challenge. We investigated whether pre-forming acetylcholine receptor (AChR) clusters on engineered muscle fibers using an AChR cluster-inducing factor (agrin) prior to implantation would facilitate established contacts between implanted muscle tissues and nerves and result in rapid innervation of engineered muscle in vivo. We showed that agrin treatment significantly increased the formation of AChR clusters on culture differentiated myotubes (C2C12), enhanced contacts with nerves in vitro and in vivo, and increased angiogenesis. Pre-fabrication of AChR clusters on engineered skeletal muscle using a released neurotrophic factor can accelerate innervations following implantation in vivo. This technique has considerable potential for enhancing muscle tissue function.
authors: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
authors: In Kap
authors: IK
authors: Ko
authors: Bu-Kyu
authors: BK
authors: Lee
authors: Sang Jin
authors: SJ
authors: Lee
authors: Karl-Erik
authors: KE
authors: Andersson
authors: Anthony
authors: A
authors: Atala
authors: James J
authors: JJ
authors: Yoo
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D018171:Agrin / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D018929:Cell Culture Techniques; D002642:Chick Embryo; D021621:Imaging, Three-Dimensional; D008297:Male; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011923:Rats, Nude; D011950:Receptors, Cholinergic / Q000378:metabolism*; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D018171:Agrin; D011950:Receptors, Cholinergic; D000109:Acetylcholine; D002118:Calcium