In Vivo Myogenic Potential of Human CD133+ Muscle-derived Stem Cells: A Quantitative Study

Abstract

In recent years, numerous reports have identified in mouse different sources of myogenic cells distinct from satellite cells that exhibited a variable myogenic potential in vivo. Myogenic stem cells have also been described in humans, although their regenerative potential has rarely been quantified. In this study, we have investigated the myogenic potential of human muscle-derived cells based on the expression of the stem cell marker CD133 as compared to bona fide satellite cells already used in clinical trials. The efficiency of these cells to participate in muscle regeneration and contribute to the renewal of the satellite cell pool, when injected intramuscularly, has been evaluated in the Rag2(-/-) gammaC(-/-) C5(-/-) mouse in which muscle degeneration is induced by cryoinjury. We demonstrate that human muscle-derived CD133+ cells showed a much greater regenerative capacity when compared to human myoblasts. The number of fibers expressing human proteins and the number of human cells in a satellite cell position are all dramatically increased when compared to those observed after injection of human myoblasts. In addition, CD133+/CD34+ cells exhibited a better dispersion in the host muscle when compared to human myoblasts. We propose that muscle-derived CD133+ cells could be an attractive candidate for cellular therapy.

Satellite Cells and the Muscle Stem Cell Niche

“…A small subpopulation of CD133 ϩ / CD34 ϩ double positive cells can be identified in the blood and skeletal muscle interstitium (233). Similar to blood-derived CD133 ϩ cells, human muscle-derived CD133 ϩ cells manifested remarkable myogenic differentiation capacity in regenerating muscle (372). As CD133 ϩ cells can be readily isolated from the blood, manipulated in vitro and delivered through the circulation, a couple of studies have explored their application to treating Duchenne muscular dystrophy (DMD).…”

Cell Transplantation and “Stem Cell Therapy” in the Treatment of Myopathies: Many Promises in Mice, Few Realities in Humans

“…Other human-derived cells that were reported to form donor-derived satellite cells following transplantation in immunodeficient mice, with different efficiency, were muscle-derived CD133+ cells [38], muscle-derived aldehydedehydrogenase+ cells [39], and intra-arterially delivered pericytes [40].…”

“…Another possibility (more accessible to laboratories that do not have access to irradiation equipment) is cryodamage. In this case, freezing the recipient muscles combines myofiber necrosis with killing the recipient's satellite cells, and it was used in mice as a pretreatment to increase the engraftment of the implanted myogenic cells [21,22,36,38].…”

Stem Cell Based Therapy for Muscular Dystrophies: Cell Types and Environmental Factors Influencing Their Efficacy

“…Therefore, if the transplanted stem cell is located a distance away, it may not either receive the correct signals, or be able to migrate to the damaged fibers. As many of these injury regimes are very severe, for example, cryoinjury (Brimah et al, 2004;Irintchev et al, 1997;Negroni et al, 2009) or use of snake venoms (Lefaucheur & Sebille, 1995;Silva-Barbosa et al, 2005) to induce degeneration and regeneration in host muscles, they could not be used in patients. Even in dystrophin-deficient mdx nu/nu host mice, satellite cells contribute little, if any, to muscle regeneration (Boldrin et al, 2009;Collins et al, 2005) although myoblasts contribute to muscle regeneration to a greater extent ( Morgan et al, 2002;Partridge et al, 1989).…”