New Perspectives in Regeneration

Steward MM, Sridhar A, Meyer JS, Melissa M. Steward, Akshayalakshmi Sridhar, Jason S. Meyer, Steward, Melissa M., Sridhar, Akshayalakshmi, Meyer, Jason S.

Regeneration of the nervous system requires either the repair or replacement of nerve cells that have been damaged by injury or disease. While lower organisms possess extensive capacity for neural regeneration, evolutionarily higher organisms including humans are limited in their ability to regenerate nerve cells, posing significant issues for the treatment of injury and disease of the nervous system. This chapter focuses on current approaches for neural regeneration, with a discussion of traditional methods to enhance neural regeneration as well as emerging concepts within the field such as stem cells and cellular reprogramming. Stem cells are defined by their ability to self-renew as well as their ability to differentiate into multiple cell types, and hence can serve as a source for cell replacement of damaged neurons. Traditionally, adult stem cells isolated from the hippocampus and subventricular zone have served as a source of neural stem cells for replacement purposes. With the advancement of pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs), new and exciting approaches for neural cell replacement are being developed. Furthermore, with increased understanding of the human genome and epigenetics, scientists have been successful in the direct genetic reprogramming of somatic cells to a neuronal fate, bypassing the intermediary pluripotent stage. Such breakthroughs have accelerated the timing of production of mature neuronal cell types from a patient-specific somatic cell source such as skin fibroblasts or mononuclear blood cells. While extensive hurdles remain to the translational application of such stem cell and reprogramming strategies, these approaches have revolutionized the field of regenerative biology and have provided innovative approaches for the potential regeneration of the nervous system.