Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta
Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta
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DOI：
10.1038/6529
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发表时间：
1999-03-01
期刊：
影响因子：
82.9
通讯作者：
Brenner, MK
中科院分区：
文献类型：
--
作者：
Horwitz, EM;Prockop, DJ;Brenner, MK
原则上，间充质祖细胞的移植将减轻或可能纠正骨、软骨和肌肉的遗传疾病，但缺乏对这一概念的临床支持。在这里，我们描述了异基因骨髓移植的初步结果，在三个儿童成骨不全，遗传性疾病，其中成骨细胞产生有缺陷的I型胶原蛋白，导致骨量减少，多发性骨折，严重的骨畸形和相当短的身材。成骨细胞植入后3个月（1.5-2.0%供体细胞），骨小梁的代表性标本显示组织学变化，表明新的致密骨形成。所有患者的全身骨矿物质含量增加了21至29克（中位数为28），而体重变化相似的健康儿童的预测值为0至4克（中位数为0）。这些改善与生长速度的增加和骨折频率的降低有关。因此，同种异体骨髓移植可以导致功能性间充质祖细胞的植入，表明这种策略在治疗成骨障碍和其他间充质干细胞疾病中的可行性。
In principle, transplantation of mesenchymal progenitor cells would attenuate or possibly correct genetic disorders of bone, cartilage and muscle, but clinical support for this concept is lacking. Here we describe the initial results of allogeneic bone marrow transplantation in three children with osteogenesis imperfecta, a genetic disorder in which osteoblasts produce defective type I collagen, leading to osteopenia, multiple fractures, severe bony deformities and considerably shortened stature. Three months after osteoblast engraftment (1.5-2.0% donor cells), representative specimens of trabecular bone showed histologic changes indicative of new dense bone formation. All patients had increases in total body bone mineral content ranging from 21 to 29 grams (median, 28), compared with predicted values of 0 to 4 grams (median, 0) for healthy children with similar changes in weight. These improvements were associated with increases in growth velocity and reduced frequencies of bone fracture. Thus, allogeneic bone marrow transplantation can lead to engraftment of functional mesenchymal progenitor cells, indicating the feasibility of this strategy in the treatment of osteogenesis imperfecta and perhaps other mesenchymal stem cell disorders as well.