Stem cell plasticity: from transdifferentiation to macrophage fusion

Abstract

The past 5 years have witnessed an explosion of interest in using adult-derived stem cells for cell and gene therapy. This has been driven by a number of findings, in particular, the possibility that some adult stem cells can differentiate into non-autologous cell types, and also the discovery of multipotential stem cells in adult bone marrow. These discoveries suggested a quasi-alchemical nature of cells derived from adult organs, thus raising new and exciting therapeutic possibilities. Recent data, however, argue against the whole idea of stem cell 'plasticity', and bring into question the therapeutic strategies based upon this concept. Here, we will review the current state of knowledge in the field and discuss some of the clinical implications.

Figure 1

Model for the mechanism of bone marrow‐derived myogenesis. HSC from bone marrow produce circulating myeloid cells. In response to muscle injury, these cells are recruited to the site of damage and function as inflammatory cells. Amidst a regenerative and active fusogenic milieu, a very small number of infiltrating cells randomly become incorporated into a growing mature myofibre. The scheme also emphasizes the differences between bone marrow‐derived and traditional myogenesis. Whereas the latter occurs through genetically specified mononuclear muscle stem cell intermediates and mediates robust levels of contribution, the former does not involve a tissue‐specific stem cell and achieves insignificant levels of engraftment.