Mesenchymal stem cells as mediators of neural differentiation.
Mesenchymal stem cells (MSCs) represent a promising source of material for autologous cell transplantation therapies, in particular, their potential use for the treatment of damaged nervous tissue. Much of the work in this area has focused on the transplantation of MSCs into animal models of neurological disorders, including stroke and spinal cord injury. Although numerous studies have reported significant functional improvements in these systems, the exact mechanism(s) by which MSCs elicit recovery remains largely undefined. While it has been proposed that 'trans'-differentiation and/or cell fusion events underly MSC-mediated neural repair, there is considerable doubt that the low frequency of these phenomena is sufficient to account for the observed levels of recovery. Furthermore, in vitro studies call into question the ability of MSCs to produce authentic neural derivatives. In this review we focus on recent evidence indicating that transplanted MSCs promote endogenous repair of neurologically damaged areas via the release of soluble trophic factors and cytokines. Through the modern analysis of MSC-conditioned media it is becoming possible to gain new insight into the release and interplay of these soluble factors and their neurogenic effects. Ultimately this understanding may lead to the rational design of new therapies for the treatment of neurological and neurodegenerative disorders.
Hardy
Steven A
SA
ReInnervate Ltd., Durham, UK.
Maltman
Daniel J
DJ
Przyborski
Stefan A
SA
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002459:Cell Fusion; D054338:Cell Transdifferentiation / Q000502:physiology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000378:metabolism; D009422:Nervous System Diseases / Q000628:therapy; D009474:Neurons / Q000502:physiology*
D017077:Culture Media, Conditioned; D009414:Nerve Growth Factors