Synergistic effect of high-intensity interval training and stem cell transplantation with amniotic membrane scaffold on
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Synergistic effect of high‑intensity interval training and stem cell transplantation with amniotic membrane scaffold on repair and rehabilitation after volumetric muscle loss injury Mohammad Reza Izadi1 · Abdolhamid Habibi1 · Zahra Khodabandeh2 · Masood Nikbakht1 Received: 18 May 2019 / Accepted: 14 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Despite the high regenerative capacity of skeletal muscle, volumetric muscle loss (VML) is an irrecoverable injury. One therapeutic approach is the implantation of engineered biologic scaffolds enriched with stem cells. The objective of this study is to investigate the synergistic effect of high-intensity interval training (HIIT) and stem cell transplantation with an amniotic membrane scaffold on innervation, vascularization and muscle function after VML injury. A VML injury was surgically created in the tibialis anterior (TA) muscle in rats. The animals were randomly assigned to three groups: untreated negative control group (untreated), decellularized human amniotic membrane bio-scaffold group (dHAM) and dHAM seeded with adipose-derived stem cells, which differentiate into skeletal muscle cells (dHAM-ADSCs). Then, each group was divided into sedentary and HIIT subgroups. The exercise training protocol consisted of treadmill running for 8 weeks. The animals underwent in vivo functional muscle tests to evaluate maximal isometric contractile force. Regenerated TA muscles were harvested for molecular analyses and explanted tissues were analyzed with histological methods. The main finding was that HIIT promoted muscle regeneration, innervation and vascularization in regenerated areas in HIIT treatment subgroups, especially in the dHAM-ADSC subgroup. In parallel with innervation, maximal isometric force also increased in vivo. HIIT upregulated neurotrophic factor gene expression in skeletal muscle. The amniotic membrane bio-scaffold seeded with differentiated ADSC, in conjunction with exercise training, improved vascular perfusion and innervation and enhanced the functional and morphological healing process after VML injury. The implications of these findings are of potential importance for future efforts to develop engineered biological scaffolds and for the use of interval training programs in rehabilitation after VML injury. Keywords Biologic scaffold · Skeletal muscle regeneration · Neurotrophic factor · Innervation · Tissue engineering
Introduction Volumetric muscle loss (VML) is defined as the surgical or traumatic loss of a major part of a skeletal muscle, resulting in an irrecoverable injury. The replacement of myofibers with fibrotic tissue in the injured area impairs muscle structure and function (Liu et al. 2018; Wu et al. 2012). After injury, long-term dysfunction causes permanent disability * Mohammad Reza Izadi m‑[email protected] 1
Faculty of Physical Education and Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
Stem Cells Technology Research Center, Shiraz University of Medi
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