Mesenchymal Stromal Cells and Their Secretome: New Therapeutic Perspectives for Skeletal Muscle Regeneration

Abstract

Mesenchymal stromal cells (MSCs) are multipotent cells found in different tissues: bone marrow, peripheral blood, adipose tissues, skeletal muscle, perinatal tissues, and dental pulp. MSCs are able to self-renew and to differentiate into multiple lineages, and they have been extensively used for cell therapy mostly owing to their anti-fibrotic and immunoregulatory properties that have been suggested to be at the basis for their regenerative capability. MSCs exert their effects by releasing a variety of biologically active molecules such as growth factors, chemokines, and cytokines, either as soluble proteins or enclosed in extracellular vesicles (EVs). Analyses of MSC-derived secretome and in particular studies on EVs are attracting great attention from a medical point of view due to their ability to mimic all the therapeutic effects produced by the MSCs (i.e., endogenous tissue repair and regulation of the immune system). MSC-EVs could be advantageous compared with the parental cells because of their specific cargo containing mRNAs, miRNAs, and proteins that can be biologically transferred to recipient cells. MSC-EV storage, transfer, and production are easier; and their administration is also safer than MSC therapy. The skeletal muscle is a very adaptive tissue, but its regenerative potential is altered during acute and chronic conditions. Recent works demonstrate that both MSCs and their secretome are able to help myofiber regeneration enhancing myogenesis and, interestingly, can be manipulated as a novel strategy for therapeutic interventions in muscular diseases like muscular dystrophies or atrophy. In particular, MSC-EVs represent promising candidates for cell free-based muscle regeneration. In this review, we aim to give a complete picture of the therapeutic properties and advantages of MSCs and their products (MSC-derived EVs and secreted factors) relevant for skeletal muscle regeneration in main muscular diseases.

The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration

“…Mice with reduced muscle miRNAs (eliminated Dicer activity, specifically in muscles) showed decreased skeletal muscle mass and increased myoblast apoptosis, as well as abnormal myofiber morphology [ 95 ]. miRNAs circulating in the blood are sensitive to RNase and the oxidative extracellular environment [ 11 , 96 ]; thus, they are normally bound to proteins or protected by exosomes [ 97 , 98 ].…”

Insight in Hypoxia-Mimetic Agents as Potential Tools for Mesenchymal Stem Cell Priming in Regenerative Medicine

“…Practical methods for differentiating murine iPSC-derived cardiomyocytes, combining hypoxia and bioreactor controlling culture conditions, have already been described [ 158 ]. Extracellular vesicles (EVs) are attracting the attention of researchers because of their ability to mimic all the therapeutic effects induced by the MSCs (e.g., anti-inflammatory, proangiogenic, or antifibrotic) [ 159 ]. Thus, MSC-derived EVs can modulate tissue response to a broad spectrum of injuries [ 160 ] and are considered a substitute for cell-based therapies.…”

The Functions and Mechanisms of Low-Level Laser Therapy in Tendon Repair (Review)

“…While MSCs have considerable benefits in musculoskeletal disorders, there is still a certain risk of infection during the healing process. The effectiveness of MSCs have mostly been verified through animal studies; hence, we still require a wealth of in vivo trials to demonstrate the effectiveness of ASCs therapy ( Sandona et al, 2021 ).…”