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Evaluation of adipose-derived stem cells for tissue-engineered muscle repair construct-mediated repair of a murine model of volumetric muscle loss injury

Authors Kesireddy V

Received 17 December 2015

Accepted for publication 18 February 2016

Published 8 April 2016 Volume 2016:11 Pages 1461—1473

DOI https://doi.org/10.2147/IJN.S101955

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lucy Goodman

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Thomas J Webster

Venu Kesireddy1,2

1Wake Forest Institute for Regenerative Medicine, Wake Forest University Baptist Medical Center, Winston Salem, NC, USA; 2Center for Craniofacial Research, School of Dentistry, University of Texas Health Science Center at Houston, Houston, TX, USA

Abstract:
Volumetric muscle loss (VML) can occur from congenital defects, muscle wasting diseases, civilian or military injuries, and as a result of surgical removal of muscle tissue (eg, cancer), all of which can lead to irrevocable functional and cosmetic defects. Current tissue engineering strategies to repair VML often employ muscle-derived progenitor cells (MDCs) as one component. However, there are some inherent limitations in their in vitro culture expansion. Thus, this study explores the potential of adipose-derived stem cells (ADSCs) as an alternative cell source to MDCs for tissue engineering of skeletal muscle. A reproducible VML injury model in murine latissimus dorsi muscle was used to evaluate tissue-engineered muscle repair (TEMR) constructs incorporating MDCs or ADSCs. Importantly, histological analysis revealed that ADSC-seeded constructs displayed regeneration potential that was comparable to those seeded with MDCs 2 months postrepair. Furthermore, morphological analysis of retrieved constructs demonstrated signs of neotissue formation, including cell fusion, fiber formation, and scaffold remodeling. Immunohistochemistry demonstrated positive staining for both structural and functional proteins. Positive staining for vascular structures indicated the potential for long-term neotissue survival and integration with existing musculature. Qualitative observation of lentivirus-Cherry-labeled donor cells by immunohistochemistry indicates that participation of ADSCs in new hybrid myofiber formation incorporating donor cells was relatively low, compared to donor MDCs. However, ADSCs appear to participate in vascularization. In summary, I have demonstrated that TEMR constructs generated with ADSCs displayed skeletal muscle regeneration potential comparable to TEMR–MDC constructs as previously reported.

Keywords: skeletal muscle regeneration, muscle-derived progenitor cells, immunomodulation, paracrine signaling

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