Gamradt Seth C, Lieberman Jay R
Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Ann Biomed Eng. 2004 Jan;32(1):136-47. doi: 10.1023/b:abme.0000007798.78548.b8.
Orthopaedic surgeons are often faced with difficult bone loss problems. Conventional bone grafting is usually accomplished with autogenous iliac crest bone graft that provides osteogenic cells, osteoinductive growth factors, and an osteoconductive matrix. Cadaveric bone allograft and bone graft substitutes are inferior to autogenous bone graft because they fail to supply osteogenic cells or a significant amount of osteoinductive growth factors. Recombinant growth factors such as bone morphogenetic protein-2 and osteogenic protein-1 are currently in clinical use but these proteins require supraphysiologic dosing and considerable expense while failing to provide a sustained osteoinductive signal at the implantation site. Mesenchymal stem cells capable of differentiating into mesodermal tissues have been isolated and expanded in culture from several different sources including bone marrow, adipose tissue, and muscle. In the presence of appropriate growth factors these cells can differentiate into osteoblast lineage cells that will form bone in vitro and in vivo. Recent attention has focused on genetic modification of mesenchymal stem cells to both produce and respond to osteogenic growth factors with the goal of developing a tissue engineering strategy for bone repair. This review examines the current potential and limitations of these cellular systems for bone repair.
骨科医生常常面临棘手的骨缺损问题。传统的骨移植通常采用自体髂嵴骨移植，其能提供成骨细胞、骨诱导生长因子和骨传导基质。尸体同种异体骨移植和骨移植替代物不如自体骨移植，因为它们无法提供成骨细胞或大量的骨诱导生长因子。重组生长因子如骨形态发生蛋白-2和成骨蛋白-1目前正在临床使用，但这些蛋白质需要超生理剂量且费用高昂，同时无法在植入部位提供持续的骨诱导信号。能够分化为中胚层组织的间充质干细胞已从包括骨髓、脂肪组织和肌肉在内的几种不同来源中分离出来并在培养中扩增。在适当的生长因子存在下，这些细胞可分化为成骨细胞系细胞，在体外和体内形成骨。最近的研究重点是对间充质干细胞进行基因改造，使其既能产生又能响应成骨生长因子，目的是开发一种用于骨修复的组织工程策略。这篇综述探讨了这些细胞系统在骨修复方面当前的潜力和局限性。
