A key dilemma in stem-cell-based therapy for autism treatment is whether endogenous or exogenous MSC administration is the best way of stem cell delivery. Endogenous strategy could be limited by the availability of MSCs. Exogenous MSCs could show low rate of engraftment to provide cellular replacement. It is unclear if differentiated
cells are able to develop functional interconnections with the intrinsic cells of the recipient host [49]. Controversy, few exogenous MSCs are able to exert paracrine activity. Indeed, exogenously applied MSCs have been shown to
home to injured tissues and repair them by producing chemokines, or by cell or nuclear fusion with host cells [71]. On the other hand, exogenous culture-expandedMSCs could
address endogenous MSCs in order to activate them and guide intrinsic repair [72]. In addition, exogenous delivery bypasses surgical intervention on the autistic child.