Skeletal muscle-derived Human Mesenchymal Stem Cells: influence of different culture conditions on proliferative and myogenic capabilities

Abstract

Skeletal muscle tissue is characterized by restrained self-regenerative capabilities, being ineffective in relation to trauma extension both in time span (e.g. chronic diseases) and in size (e.g. large trauma). For these reasons, tissue engineering and/or cellular therapies represent a valuable solution in the cases where the physiological healing process failed. Satellite cells, the putative skeletal muscle stem cells, have been the first solution explored to remedy the insufficient self-regeneration capacity. Nevertheless, some limitation related to donor age, muscle condition, expansion hitch and myogenic potentiality maintenance have limited their use as therapeutic tool. To overcome this hindrance, different stem cells population with myogenic capabilities have been investigated to evaluate their real potentiality for therapeutic approaches, but, as of today, the perfect cell candidate has not been identified yet.In this work, we analyze the characteristics of skeletal muscle-derived human Mesenchymal Stem Cells (hMSCs), showing the maintenance/increment of myogenic activity upon differential culture conditions. In particular, we investigate the influence of a commercial enriched growth medium (Cyto-Grow), and of a medium enriched with either human-derived serum (H.S.) or Platelet-rich Plasma (PrP), in order to set up a culture protocol useful for employing this cell population in clinical therapeutic strategies. The presented results reveal the remarkable effects of H.S. in the enhancement of hMSC proliferation and myogenic differentiation.

Distinct human skeletal muscle-derived CD90 progenitor subsets for myo-fibro-adipogenic disease modeling and treatment in multiplexed conditions

“…Although primary cells deliver more relevant outcomes than cell lines, derivation of cultured primary cells from different donors or various muscle types selected for biopsy might increase the variability of experimental outcomes, as they respond differently to culture inductions. Additionally, the characteristics of primary cells change with each subsequent passage (Goloviznina et al, 2020;Testa et al, 2020). Combined, our studies address these experimental challenges and present a novel human muscle progenitor-based platform that allows examination of the potential therapeutic effects of a candidate drug in an environment of multiplexed signals.…”

“…The remarkable capacity of skeletal muscle to regenerate following injury can be severely impaired due to massive muscle wasting caused by repetitive trauma, tendon tears, and chronic injury (Testa et al, 2020;Subhash et al, 2022). Rotator cuff (RC) disorders are characterized by prolonged damage to shoulder tendons and muscles.…”

“…Often, the expression of distinctive markers that typify distinguished tissue incorporated cell subsets rapidly changes in cultures post cell isolation. For example, the mesodermal precursors, perivascular adventitial cells, lose the expression of CD34 in cultures (Corselli et al, 2012) while CD56 + myogenic progenitors acquire high expression of CD90 at passage 0 (Testa et al, 2020). We therefore tested an alternative strategy for identifying different cell populations that can be utilized as platforms for drug testing in cultures to complement pre-clinical animal studies.…”