Bioengineered human skeletal muscle capable of functional regeneration
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RESEARCH ARTICLE
Open Access
Bioengineered human skeletal muscle capable of functional regeneration J. W. Fleming , A. J. Capel, R. P. Rimington, P. Wheeler, A. N. Leonard, N. C. Bishop, O. G. Davies and M. P. Lewis*
Abstract Background: 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. Keywords: Skeletal muscle, Regeneration, Tissue engineering, Satellite cell
Background Skeletal muscle possesses an innate and robust capacity to regenerate following injury, with most injuries regenerating the tissue to a state indistinguishable from that prior to injury [1]. This regenerative capacity in vivo relies upon the presence of a resident stem cell population, satellite cells (SCs), which reside between the plasma membrane (sarcolemma) of muscle fibres and the encasing basement membrane [2–4]. SCs are characterised by * Correspondence: [email protected] School of Sports, Exercise and Health Sciences, Loughborough University, Loughborough LE11 3TU, UK
the unique position they occupy within the tissue, but also the expression of the stem cell transcription factor Pax7 [5]. Following injury SCs are activated and proliferate readily [6], producing committed myogenic precursor cells (MPCs) marked by the presence of MyoD exp
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