Tiam Mana Saffari

168 CHAPTER 8 tissue, bone, muscle, and cartilage 61 and serve as targets for genetic modification. Depending on the appropriate stimuli and environmental conditions, MSCs have shown to express plasticity and transdifferentiation and can be differentiated into non-mesenchymal lineages, such as neurons, astrocytes, Schwann-cell like cells and myelinating cells of the peripheral nervous system to enhance nerve regeneration 4,12,53,62 . Bone marrow-derived and adipose-derived MSCs are the most commonly used stem cells for PNI. Bone marrow-derived mesenchymal stem cells Bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into non- mesodermal lineages such as neurons, astrocytes, and Schwann-like cells under appropriate environmental conditions 62 . Consequently, BMSCs may enhance neurite outgrowth and express neurotrophic factors (NGF, BDNF, glial cell line-derived neurotrophic factor (GDNF), and ciliary neurotrophic factor) as well as extracellular matrix components including collagen, fibronectin, and laminin. Administration of BMSCs to nerves contributes to enhanced angiogenesis 52,63-66 . A number of studies in rodent models have found that BMSC application to conduits and acellular nerve grafts resulted in superior functional outcomes in nerve regeneration compared to untreated grafts 51,53 . BMSCs demonstrated dose-dependent enhancement of the extent of myelination, thickness of myelin sheath, and axonal thickness in a rat sciatic nerve model 67 . When cultured, BMSCs lack immune recognition and have immunosuppressive action, which may overcome induced immune rejection after allogenic transplantation 52,68 . Although BMSCs are more easily harvested than ESCs and NSCs and have minimal ethical use issues, BMSCs have inferior proliferation capacity and differentiation potential. The harvesting procedure is invasive and painful for donors and the quantity of stem cells obtained is lower compared to other sources 12,53 . Adipose-derived mesenchymal stem cells Adipose-derived mesenchymal stem cells (ADSCs) can easily be harvested from abundant adipose tissue with minimally invasive procedures such as liposuction. Compared to BMSCs, ADSCs show superior stem cell fraction, proliferation, and differentiation potential. ADSCs can be differentiated into a Schwann cell-like phenotype, sharing functional and morphological characteristics, and similar effectivity levels as autologous Schwann cells. It is postulated that ADSCs facilitate endogenous Schwann cell recruitment by expressing growth factors such as NGF, VEGF,