Stem Cells for the Treatment of Skeletal Muscle Injury

Abstract

Skeletal muscle injuries are extremely common, accounting for up to 35-55% of all sports injuries and quite possibly impacting all musculoskeletal traumas. These injuries result in the formation of fibrosis that may lead to development of painful contractures, increases their risk for repeat injuries, and limits their ability to return to a baseline or pre-injury level of function. The development of successful therapies for these injuries must consider the pathophysiology of these musculoskeletal conditions. We discuss the direct use of muscle-derived stem cells and some key cell population dynamics, as well as the use of clinically applicable modalities which may enhance the local supply of stem cells to the zone of injury by promoting angiogenesis.

MRI of Muscle Injuries

“…Scar formation may inhibit innervation of regenerating muscle tissue and reduce muscle contractility and range of motion (Quintero et al 2009). The developing scar is the weakest point for recurrent tears up to 12 days post injury.…”

Return to sport after muscle injury

“…The occurrence of fibrosis causes pain and mechanical stiffness, limiting the contractile force of the muscle tissue and decreasing the patient's range of motion [19]. Recently, the cytokine TGF-ß has been implicated in the accumulation of fibrotic tissue within muscle after skeletal muscle injuries [20].…”

“…Muscle-derived stem cells have been proposed as a treatment for skeletal muscle injury [19]. In a controlled laboratory study, MDSC were injected into injured tibialis anterior muscles of mice at several time points after muscle contusion injury [57].…”

Biologic scaffolds for musculotendinous tissue repair

“…A number of other myogenic stem cell populations have also been identified which are distinct from satellite cells, although the precise origin, identity and location of these cells remain speculative. These include myogenic progenitor cells characterized as CD56+, CD34-, CD144-, CD45-and CD146-; myo-endothelial cells characterized as CD56+, CD34+, CD144+, CD45-and CD146-; perivascular progenitor cells characterized as CD56-, CD34-, CD144-, CD45-and CD146+; and a muscle-derived side population (MDSP) that has similar properties to hematopoietic stem cells in the bone marrow (Crisan et al, 2009;Deasy et al, 2004;Huard, 2008;Kallestad and McLoon, 2010;Lecourt et al, 2010;Peault et al, 2007;Qu-Petersen et al, 2002;Quintero et al, 2009;Ten Broek et al, 2010;Usas and Huard, 2007;Wu et al, 2010). The number of MDSCs increases rapidly following muscle trauma (Jackson et al, 2011;Nesti et al, 2008).…”

“…Furthermore, some fibroblasts differentiate into contractile myofibroblasts, which contribute to wound contraction. There is intense interest, and controversy, regarding the contribution of stem and progenitor cell populations, such as bone marrow derived cells, to tissue repair either through differentiation or by secretion of paracrine factors that affect surrounding cells (Quintero et al, 2009;Sun et al, 2009;Tedesco et al, 2010;Ten Broek et al, 2010). …”