Dual roles of mesenchymal stem cells in spinal cord injury: Cell replacement therapy and as a model system to understand axonal repair

Mesenchymal stem cells (MSC) are pluripotent cells that differentiate into cells of mesodermal origin and transdifferentiate into ectodermal and endodermal cell types. MSC can transdifferentiate with high efficiency to functional neurons, microglia and oligodendrocytes. MSC and neurons can respond to environmental cues such as cytokines, which also affect the development to neural cells. Since cytokines and other inflammatory mediators are also expected at sites of spinal cord injury (SCI), simple implantation of MSC and/or their differentiated cells might be premature unless the basic science precedes translational science. This is particularly true since an individual's immune response might be unique. Similar argument could be made for embryonic stem cells (ESC). The unstable behavior of ESC to form tumors, as well as rapid generation of mixed cell types makes MSC desirable stem cells for translational science. This review discusses varied interdisciplinary approaches by which MSC can be applied to SCI repair, including bioengineering approach. The mechanism by which microenvironmental factors such as inflammatory mediators can affect stem cell therapies is also discussed. In addition to the potential of direct application of stem cells or their differentiated cells, MSC can be used as models to understand axonal repair, which could lead to the development of new drugs for SCI. The model could test novel factors to repair neurons. Any identified factor could be delivered directly or by gene therapy. The co-culture method is significant to long-term investigation for rapid screening of compounds, with simultaneous understanding of repair mechanisms of axotomized neurons. The model could be translated in parallel with other stem cell therapies for SCI repair. We also discuss the potential of stem cell therapies for other neurodegenerative diseases.