[Genetic basis for skeletal disease. Stem cell therapy for genetic bone disorders]

Mesenchymal stem cells (MSCs) can show osteogenic differentiation capability when implanted in vivo , as well as cultured in vitro; therefore we attempted to use allogeneic MSCs for a patient with hypophosphatasia, which is caused by mutations in tissue non-specific alkaline phosphatase (TNSALP) gene. Donor MSCs were obtained by culture expansion of fresh marrow from the patient's father. Some of the MSCs were further cultured under osteogenic conditions on a culture dish or porous hydroxyapatite ceramics, resulting in cultured osteoblasts and osteogenic constructs, respectively. After traditional bone marrow transplantation, The donor MSCs and osteoblasts were injected into the patient and the constructs were implanted subcutaneously or intraosseous lesions. The patient's respiratory condition improved and donor cells were detected in newly formed bone tissue. These findings showed the importance of allogeneic MSC transplantation for the hypophosphatasia patient.