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Bioengineered human skeletal muscle capable of functional regeneration
journal contribution
posted on 2020-10-30, 12:02 authored by Jacob Fleming, Andrew CapelAndrew Capel, Rowan Rimington, Patrick WheelerPatrick Wheeler, Amber Leonard, Nicolette BishopNicolette Bishop, Owen DaviesOwen Davies, Mark LewisMark LewisBackground: Skeletal muscle (SkM) regenerates following injury, replacing damaged tissue with high fidelity. However, in serious injuries, non-regenerative defects leave patients with loss of function, increased re-injury risk and often chronic pain. Progress in treating these non-regenerative defects has been slow, with advances only occurring where a comprehensive understanding of regeneration has been gained. Tissue engineering has allowed the development of bioengineered models of SkM which regenerate following injury to support research in regenerative physiology. To date, however, no studies have utilised human myogenic precursor cells (hMPCs) to closely mimic functional human regenerative physiology.
Results: Here we address some of the difficulties associated with cell number and hMPC mitogenicity using magnetic association cell sorting (MACS), for the marker CD56, and media supplementation with fibroblast growth factor 2 (FGF-2) and B-27 supplement. Cell sorting allowed extended expansion of myogenic cells and supplementation was shown to improve myogenesis within engineered tissues and force generation at maturity. In addition, these engineered human SkM regenerated following barium chloride (BaCl2) injury. Following injury, reductions in function (87.5%) and myotube number (33.3%) were observed, followed by a proliferative phase with increased MyoD+ cells and a subsequent recovery of function and myotube number. An expansion of the Pax7+ cell population was observed across recovery suggesting an ability to generate Pax7+ cells within the tissue, similar to the self-renewal of satellite cells seen in vivo.
Conclusions: This work outlines an engineered human SkM capable of functional regeneration following injury, built upon an open source system adding to the pre-clinical testing toolbox to improve the understanding of basic regenerative physiology.
Funding
DTP 2016-2017 Loughborough University
Engineering and Physical Sciences Research Council
Find out more...History
School
- Sport, Exercise and Health Sciences
Published in
BMC BiologyVolume
18Issue
1Pages
16Publisher
BioMed Central Ltd. Part of Springer Nature.Version
- VoR (Version of Record)
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© The Author(s)Acceptance date
2020-09-30Publication date
2020-10-20Copyright date
2020eISSN
1741-7007Publisher version
Language
- en
Location
EnglandDepositor
Deposit date: 30 October 2020Article number
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