Clinical Impact of Circulating CD34-Positive Cells on Bone Regeneration and Healing

Clinical Impact of Circulating CD34-Positive Cells on Bone Regeneration and Healing
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DOI:
10.1089/ten.teb.2013.0511
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发表时间:
2014-06-01
影响因子:
6.4
通讯作者:
Kurosaka, Masahiro
Kurosaka, Masahiro
中科院分区:
医学2区
文献类型:
--
作者:
Kuroda, Ryosuke;Matsumoto, Tomoyuki;Kurosaka, Masahiro

文献摘要

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传统的自体骨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,近年来在骨再生和修复中的注意力集中在干细胞如骨髓间充质干细胞和循环骨骼干细胞的使用上。循环干细胞由于其易于临床应用和高的成骨和血管生成潜力而受到广泛关注。在这份报告中,我们重点介绍了第一个证明原理的实验,证明了循环CD 34(+)细胞的协同特性,称为内皮和造血祖细胞丰富的人口,能够分化为内皮细胞和成骨细胞。移植循环中的CD 34(+)细胞通过血管生成/血管生成和成骨为骨折愈合提供有利的环境,最终导致骨折的功能恢复。在一系列基础研究的基础上,我们进行了自体CD 34(+)细胞移植治疗胫骨或股骨骨不连患者的1/2期临床试验,并报告了这种新疗法的安全性和有效性。本文就循环CD 34(+)细胞治疗的概念、策略及其在骨修复中的应用前景作一综述。
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.