Abstract
Skeletal muscle tissue engineering constitutes an emerging therapeutic repair strategy aiming for structural and functional restoration following traumatic injury, deep burns, congenital malformation or surgical tumor removal. As for similar musculoskeletal acute and degenerative affections, allogenic progenitor cell therapy represents a promising clinical approach to synergistically supplement traditional surgical care. Preliminary studies have established the adequation of primary human fetal muscle progenitors (hFMPs) for applications in regenerative medicine. Such therapeutic cell sources combined with bioresorbable scaffolds optimally integrate in murine muscle injury models without causing immune rejection. The present work aimed at functional recovery assessment following standardized application of hFMPs in an optimized murine skeletal muscle wound model. Cryopreserved hFMPs were initiated and culture-expanded before seeding in equine collagen scaffolds. Gastrocnemius muscles of C57BL/6 mice were injured following a standardized protocol.
Highlights
Traditional reconstructive surgery remains a primary practical option for extensive and profound tissue defects, as no tangible alternative consolidated therapeutic solution is currently available for effective management of these complex clinical cases
Marker expression was reassessed after 5 years of cryopreservation and it was found that > 80 % of studied human fetal muscle progenitors (hFMPs) expressed 5.1H11 and desmin when cultured in 2D adherent monolayers or on 3D collagen scaffolds, providing capital information about cell population identity and purity evolution (Figure 3A). 2D cultures reached 90 % confluency in 14 days, whereas cell counts in the collagen scaffolds increased 6-fold in the same time
Equine collagen scaffolds were confirmed as well adapted for therapeutic cell delivery of hFMPs, as both cyto and biocompatibility were extensively studied in the context of Progenitor Biological Bandages (PBBs) clinical applications and results appear to be similar with progenitor muscle cells based on this study [19,20,21,22]
Summary
Traditional reconstructive surgery remains a primary practical option for extensive and profound tissue defects, as no tangible alternative consolidated therapeutic solution is currently available for effective management of these complex clinical cases. Congenital malformation, burn wounds or surgical tumor removal potentially cause or lead to such significant defects, drastically impacting both structure and function of cutaneous, subcutaneous and musculature tissues. As long as quantitative skeletal muscle tissue loss does not exceed intrinsic self-repair capacities, newly formed and maturating myofibers may support muscle structural regeneration processes [2,4]. Critical destructive lesions of muscle tissue drastically hinder or negate spontaneous restoration of original physiological structure and properties, leading to fibrous scarring potentially impacting and restricting contractility and general function. Significant destructive muscle injuries may be defined as volumetric muscle losses (VMLs), implying the absence by removal of tissue components such as nerves, vessels, ECM, satellite and muscle cells [6,7]. Current standards of care for VML comprise free muscle transfer (with surgical vasculature and innervation restoration) or muscular transfer flap, while protocols describing myoblast transfer therapy actively occupy translational medical research [6]
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