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

Figure 1

Properties required in mononuclear precursor cells to be useful for cell transplantation in myology. The figure makes reference to myoblasts because they are the only cells in which the three properties have been demonstrated convincingly by different independent groups and are the only ones that showed at least some of them in clinical conditions. The endogenous elements are depicted in red, and the exogenous grafted elements are in blue. After intramuscular injection (a), the grafted myoblasts are collected essentially in perimysial spaces, as observed in nonhuman primates. From there, at least some of them migrate guided by chemotactic gradients ((b), the gradient is represented in gray) towards myofibers in regeneration (c). Myofiber regeneration (c) is the consequence of myofiber necrosis, which can be complete or (more frequently in myopathies and intramuscular cell transplantation) segmental (d). These migrating myoblasts are recruited in the process of myofiber regeneration, and they fuse with the endogenous myoblasts (c). Once regeneration is completed, the incorporation of the grafted myoblasts in the process of regeneration gives rise to hybrid myofibers (e). In addition to the proteins synthesized by endogenous nuclei, hybrid myofibers produce exogenous proteins around the exogenous myonuclei (e). So far, myoblasts are the only mononuclear precursor cells that were demonstrated to posses this property in clinical conditions. Some of the grafted cells, in addition, can give raise to new satellite cells (f). Finally, the grated cells can fuse between themselves (g) to give rise to neoformed myofibers (h). Our clinical observations strongly suggest that transplanted myoblasts can form small new myofibers in humans, a property that must be improved to meet a clinical role.