Tiam Mana Saffari

166 CHAPTER 8 STEM CELL SOURCES Stem cells can be categorized as embryonic stem cells or adult stem cells according to their development stage, which relates to their differentiation potential. Embryonic stem cells In 1998, Thomson et al. described the isolation of pluripotent cell lines from the inner cell mass of human blastocyst-stage embryos 50 . Following this discovery, stem cells have been harvested from several fetal as well as adult tissues (Figure 2). Embryonic stem cells (ESC) are undifferentiated cells, capable of self-renewal and have superior differentiation potential and long-term proliferation capacity compared to adult stem cells. ESCs have the ability of in vivo myelination since they can differentiate into neurons and glial cells of the central and peripheral nervous system. In humans, the use of ESCs in neural tissue engineering is primarily inhibited by the ethical controversy of the use and destruction of a human embryo. Additional limitations include ESC’s immunogenicity and carcinogenic potential including teratoma formation which limits clinical translation. Differentiation of ESCs into specialized neural cell lines remains challenging and protocols have only been established for a few cell lines 4,51-54 . Neural stem cells Neural stem cells (NSCs) are naturally capable of differentiating into neurons or glial cells and play a role during neurogenesis in the development of the brain and spinal cord, which almost exclusively occurs during embryogenesis. In human adults, NSCs are located in the subventricular zone and hippocampus and have a limited role in the regeneration of central nervous system injuries 53,55,56 . While several basic science studies suggest enhancement of nerve regeneration following NSC administration to the injury site after both acute and chronic PNI 53,57,58 , commercially available NSCs have been reported to be associated with the formation of neuroblastoma after implantation 59 . Additional limitations to application in humans include the technical difficulties associated with cell harvest and the need to direct differentiation of specialized neural cell lines. The application of NSCs could greatly benefit clinical practice if these limitations can be overcome 58 .