Adult stems cells, possessing the ability to grow, migrate, proliferate, and transdifferentiate into various specific phenotypes including, neuronal or glial cell types, constitute a great asset for biomedical applications involving peripheral nerve regeneration. Adult stem cell plasticity, in particular their ability to undergo transdifferentiation, is sensitive to various cellto- cell interactions and external stimuli involving the interactions with physical, mechanical and chemical cues within their microenvironment. Various studies have employed different techniques for transdifferentiating adult stem cells from distinct sources into specific lineages (e.g., glial cells and neurons). These techniques include using chemical and/or electrical induction as well as cell-to-cell synergetic effects via co-culture along with the use of various 3D conduit/scaffold designs. Such scaffolds consist of unique natural and/or synthetic materials that possess controllable physical/mechanical properties that can mimic the natural extracellular matrix environment of the cells. However, the current limitations regarding the final fate of implanted transdifferentiated stem cell populations, non-scalable transdifferentiation protocols, and design of a conduit/scaffold that mimics the complex extracellular matrix microenvironment have required development of new strategies for the effective transdifferentiation of stem cells and their implantation. In this progress report, we present a comprehensive review of recent advances in the transdifferentiation of adult stem cells into particularly Schwann cells or neurons via different approaches (chemical and/or electrical stimuli or co-culture with different cells) along with multifunctional conduit/scaffolds materials and designs. We also included potential cellular mechanisms and signaling pathways associated with stem cell differentiation. We conclude the discussion with some of the challenges that still need to be overcome in the field and provide an outlook toward future research directions.
Available at: http://works.bepress.com/donald-sakaguchi/33/