Human Mesenchymal Stem Cells Persist, Demonstrate Site-Specific Multipotential Differentiation, and Are Present in Sites of Wound Healing and Tissue Regeneration after Transplantation into Fetal Sheep

Prenatal transplantation of stem cells is an exciting frontier for the treatment of many congenital diseases. The fetus may be an ideal recipient for stem cells, as it is immunologically immature and has rapidly proliferating cellular compartments that may support the engraftment of transplanted cells. Mesenchymal stem cells (MSC), given their ability to differentiate into multiple cell types, could potentially be used to treat diseases such as osteogenesis imperfecta, muscular dystrophy, and other mesenchymal disorders that can be diagnosed in utero. We have shown, using a human–sheep in utero xenotransplantation model, that human MSC have the ability to engraft, undergo site-specific differentiation into multiple cell types, and survive for more than 1 year in fetal lamb recipients. In addition, in this model MSC-derived cells appear to be present in increased numbers in wounded or regenerating tissues. This observation warrants further studies of the biology of MSCs following systemic or site-directed transplantation.