Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta
Open Access
- 1 March 2001
- journal article
- Published by American Society of Hematology in Blood
- Vol. 97 (5), 1227-1231
- https://doi.org/10.1182/blood.v97.5.1227
Abstract
Preclinical models have shown that transplantation of marrow mesenchymal cells has the potential to correct inherited disorders of bone, cartilage, and muscle. The report describes clinical responses of the first children to undergo allogeneic bone marrow transplantation (BMT) for severe osteogenesis imperfecta (OI), a genetic disorder characterized by defective type I collagen, osteopenia, bone fragility, severe bony deformities, and growth retardation. Five children with severe OI were enrolled in a study of BMT from human leukocyte antigen (HLA)–compatible sibling donors. Linear growth, bone mineralization, and fracture rate were taken as measures of treatment response. The 3 children with documented donor osteoblast engraftment had a median 7.5-cm increase in body length (range, 6.5-8.0 cm) 6 months after transplantation compared with 1.25 cm (range, 1.0-1.5 cm) for age-matched control patients. These patients gained 21.0 to 65.3 g total body bone mineral content by 3 months after treatment or 45% to 77% of their baseline values. With extended follow-up, the patients' growth rates either slowed or reached a plateau phase. Bone mineral content continued to increase at a rate similar to that for weight-matched healthy children, even as growth rates declined. These results suggest that BMT from HLA-compatible donors may benefit children with severe OI. Further studies are needed to determine the full potential of this strategy.Keywords
This publication has 28 references indexed in Scilit:
- Dystrophin expression in the mdx mouse restored by stem cell transplantationNature, 1999
- Multilineage Potential of Adult Human Mesenchymal Stem CellsScience, 1999
- Collagen and Bone StrengthJournal of Bone and Mineral Research, 1999
- Cyclic Administration of Pamidronate in Children with Severe Osteogenesis ImperfectaNew England Journal of Medicine, 1998
- Muscle Regeneration by Bone Marrow-Derived Myogenic ProgenitorsScience, 1998
- Osteogenesis ImperfectaRehabilitation and Prospects for Gene TherapyJAMA, 1997
- Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice.Proceedings of the National Academy of Sciences of the United States of America, 1995
- Cellular expression of bone‐related proteins during in vitro osteogenesis in rat bone marrow stromal cell culturesJournal of Cellular Physiology, 1994
- Induction of Rapid Osteoblast Differentiation in Rat Bone Marrow Stromal Cell Cultures by Dexamethasone and BMP-2Developmental Biology, 1994
- Culture‐expanded human periosteal‐derived cells exhibit osteochondral potential in vivoJournal of Orthopaedic Research, 1991