Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine , Kobe, Japan .
Tissue Eng Part B Rev. 2014 Jun;20(3):190-9. doi: 10.1089/ten.TEB.2013.0511. Epub 2014 Feb 10.
Failures in fracture healing after conventional autologous and allogenic bone grafting are mainly due to poor vascularization. To meet the clinical demand, recent attentions in the regeneration and repair of bone have been focused on the use of stem cells such as bone marrow mesenchymal stem cells and circulating skeletal stem cells. Circulating stem cells are currently paid a lot of attention due to their ease of clinical setting and high potential for osteogenesis and angiogenesis. In this report, we focus on the first proof-of-principle experiments demonstrating the collaborative characteristics of circulating CD34(+) cells, known as endothelial and hematopoietic progenitor cell-rich population, which are capable to differentiate into both endothelial cells and osteoblasts. Transplantation of circulating CD34(+) cells provides a favorable environment for fracture healing via angiogenesis/vasculogenesis and osteogenesis, finally leading to functional recovery from fracture. Based on a series of basic studies, we performed a phase 1/2 clinical trial of autologous CD34(+) cell transplantation in patients with tibial or femoral nonunions and reported the safety and efficacy of this novel therapy. In this review, the current concepts and strategies in circulating CD34(+) cell-based therapy and its potential applications for bone repair will be highlighted.
传统自体和同种异体骨移植后骨折愈合失败主要是由于血管化不良。为了满足临床需求，最近人们对骨髓间充质干细胞和循环骨骼干细胞等干细胞在骨再生和修复中的应用给予了关注。由于循环干细胞易于临床设置和具有很强的成骨和成血管潜力，因此目前受到了广泛关注。在本报告中，我们重点介绍了第一个原理验证实验，该实验证明了循环 CD34(+)细胞（称为富含内皮细胞和造血祖细胞的群体）的协同特征，这些细胞能够分化为内皮细胞和成骨细胞。循环 CD34(+)细胞的移植通过血管生成/血管生成和成骨作用为骨折愈合提供了有利的环境，最终导致骨折的功能恢复。基于一系列基础研究，我们在胫骨或股骨骨不连患者中进行了自体 CD34(+)细胞移植的 1/2 期临床试验，并报告了这种新疗法的安全性和有效性。在这篇综述中，我们将重点介绍基于循环 CD34(+)细胞的治疗的当前概念和策略及其在骨修复中的潜在应用。
