Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone

Proceedings of the National Academy of Sciences of the United States of America - Tập 99 Số 13 - Trang 8932-8937 - 2002
Edwin M. Horwitz1, Patricia L. Gordon1, Winston K. K. Koo1, Jeffrey C. Marx1, Michael D. Neel1, René Y. McNall1, Linda Muul1, Ted J. Hofmann1
1Transplantation and Gene Therapy Program, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105; Wayne State University, 4707 St. Antoine Boulevard, Detroit, MI 48201; and Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892

Tóm tắt

Treatment with isolated allogeneic mesenchymal cells has the potential to enhance the therapeutic effects of conventional bone marrow transplantation in patients with genetic disorders affecting mesenchymal tissues, including bone, cartilage, and muscle. To demonstrate the feasibility of mesenchymal cell therapy and to gain insight into the transplant biology of these cells, we used gene-marked, donor marrow-derived mesenchymal cells to treat six children who had undergone standard bone marrow transplantation for severe osteogenesis imperfecta. Each child received two infusions of the allogeneic cells. Five of six patients showed engraftment in one or more sites, including bone, skin, and marrow stroma, and had an acceleration of growth velocity during the first 6 mo postinfusion. This improvement ranged from 60% to 94% (median, 70%) of the predicted median values for age- and sex-matched unaffected children, compared with 0% to 40% (median, 20%) over the 6 mo immediately preceding the infusions. There was no clinically significant toxicity except for an urticarial rash in one patient just after the second infusion. Failure to detect engraftment of cells expressing the neomycin phosphotransferase marker gene suggested the potential for immune attack against therapeutic cells expressing a foreign protein. Thus, allogeneic mesenchymal cells offer feasible posttransplantation therapy for osteogenesis imperfecta and likely other disorders originating in mesenchymal precursors.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 99 Số 13

8932-8937

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