Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep

Mesenchymal stem cells are multipotent cells that can be isolated from adul t bone marrow and can be induced in vitro and in vivo to differentiate into a variety of mesenchymal tissues, including bone, cartilage, tendon, fat, bone marrow stroma, and muscle(1,2). Despite their potential clinical utili ty for cellular and gene therapy, the fate of mesenchymal stem cells after systemic administration is mostly unknown. To address this, we transplanted a well-characterized human mesenchymal stem cell population(3) into fetal sheep early in gestation, before and after the expected development of immu nologic competence. In this xenogeneic system, human mesenchymal stem cells engrafted and:persisted in multiple tissues for as long as 13 months after transplantation. Transplanted human cells underwent site-specific differen tiation into chondrocytes, adipocytes, myocytes and cardiomyocytes, bone ma rrow stromal cells and thymic stroma. Unexpectedly, there was long-term eng raftment even when cells were transplanted after the expected development o f immunocompetence. Thus, mesenchymal stem cells maintain their multipotent ial capacity after transplantation, and seem to have unique immunologic cha racteristics that allow persistence in-a xenogeneic environment. Our data s upport the possibility of the transplantability of mesenchymal stem cells a nd their potential utility in tissue engineering, and cellular and gene the rapy applications.