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

TLDR

Treatment with isolated allogeneic mesenchymal cells may enhance the therapeutic effects of conventional bone marrow transplantation in patients with genetic disorders of mesenchymal tissues such as bone, cartilage, and muscle. The study aimed to demonstrate the feasibility of mesenchymal cell therapy and to explore its transplant biology by administering gene‑marked donor marrow‑derived mesenchymal cells to 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 children showed engraftment of donor mesenchymal cells in bone, skin, or marrow stroma and experienced a 60–94% increase in growth velocity compared with the preceding six months, with no major toxicity except a rash, while the lack of engraftment of neomycin phosphotransferase‑marked cells suggests possible immune rejection, supporting the feasibility of allogeneic mesenchymal cell therapy for osteogenesis imperfecta and related disorders.

Abstract

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.