Mesenchymal Stem Cell Engraftment in Bone Following In Utero Transplantation in a Patient with Severe Osteogenesis Imperfecta.

The purpose of the present study was to evaluate the ability of allogeneic fetal mesenchymal stem cells (MSCs) to engraft and differentiate after in utero transplantation. A female fetus with multiple intrauterine fractures, diagnosed as severe osteogenesis imperfecta, was transplanted with HLA-mismatched male fetal MSCs in the 32nd week of gestation. At nine months of age, whole Y genome FISH staining of a bone marrow biopsy showed a median of 7.4% Y-positive cells (range 6.8–16.6%). In slides stained for osteocalcin or osteopontin, a centromeric XY-specific probe revealed 0.3% of XY-positive cells. Bone histology showed regularly arranged and configured bone trabeculae. Patient lymphocyte proliferation against donor MSCs was not observed in in vitro co-culture experiments performed after MSC injection. Complementary bisphosphonate treatment was begun at four months. During the first two years of life three fractures were noted. At two years of corrected age, psychomotor development was normal, and growth followed the same channel, −5SD. Our findings show that allogeneic fetal mesenchymal stem cells can engraft and differentiate into bone in a human fetus even when the recipient is immunocompetent and HLA-incompatible.