Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone
Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone
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DOI：
10.1073/pnas.132252399
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发表时间：
2002-06-25
影响因子：
11.1
通讯作者：
Hofmann, T
中科院分区：
文献类型：
--
作者：
Horwitz, EM;Gordon, PL;Hofmann, T
用分离的同种异体间充质细胞治疗有可能增强传统骨髓移植在患有影响间充质组织（包括骨、软骨和肌肉）的遗传性疾病的患者中的治疗效果。为了证明间充质细胞治疗的可行性，并深入了解这些细胞的移植生物学，我们使用基因标记的供体骨髓间充质细胞治疗6名因严重成骨障碍而接受标准骨髓移植的儿童。每个孩子都接受了两次同种异体细胞的输注。6例患者中有5例显示在一个或多个部位（包括骨、皮肤和骨髓基质）植入，并且在输注后的前6个月内生长速度加快。对于年龄和性别匹配的未受影响儿童，这种改善范围为预测中值的60%至94%（中位数，70%），而在输注前6个月内为0%至40%（中位数，20%）。除1例患者在第二次输注后出现荨麻疹外，无临床显著毒性。未能检测到表达新霉素磷酸转移酶标记基因的细胞的植入，表明对表达外源蛋白的治疗性细胞的免疫攻击的潜力。因此，同种异体间充质细胞提供了可行的移植后治疗成骨不全和可能的其他疾病起源于间充质前体。
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.