Abstract
MSC have been used in diverse animal disease models to investigate their regenerative capacity. Although the clinical outcome was often encouraging, the mode of action of the cells remains unresolved. Differentiation of MSC into cell types of their target organs was only rarely shown, with the exception of the musculoskeletal system. Thus, the effect of the cells on the clinical outcome in several disease models of tissue degeneration must be independent of trans-differentiation and caused by indirect or paracrine effects. Furthermore, tracking of the cells in vivo revealed that only a small proportion of the cells home and persists in the target sites, and that most of the cells are not detectable after 7∼14 days post transplantation. It seems that MSC can deliver a profound clinical effect without trans-differentiation, without homing to target organs in significant numbers and despite the cell's disappearance within short periods of time. These finding also suggest that the full potency of MSC has not yet been exploited in the current applications. Here we will provide an overview of the different routes used for cell delivery and the fate of the cells after transplantation. The effects on clinical outcome are discussed with respect to the role cell entrapment in non-target organs may play for the observed clinical effects.