Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta

In principle, transplantation of mesenchymal progenitor cells would attenua te or possibly correct genetic disorders of bone, cartilage and muscle, but clinical support for this concept is lacking. Here we describe the initial results of allogeneic bone marrow transplantation in three children with o steogenesis imperfecta, a genetic disorder in which osteoblasts produce def ective type I collagen, leading to osteopenia, multiple fractures, severe b ony deformities and considerably shortened stature. Three months after oste oblast engraftment (1.5-2.0% donor cells), representative specimens of trab ecular bone showed histologic changes indicative of new dense bone formatio n. All patients had increases in total body bone mineral content ranging fr om 21 to 29 grams (median, 28), compared with predicted values of 0 to 4 gr ams (median, 0) for healthy children with similar changes in weight. These improvements were associated with increases in growth velocity and reduced frequencies of bone fracture. Thus, allogeneic bone marrow transplantation can lead to engraftment of functional mesenchymal progenitor cells, indicat ing the feasibility of this strategy in the treatment of osteogenesis imper fecta and perhaps other mesenchymal stem cell disorders as well.