Pericytes for the treatment of orthopedic conditions.

Pericytes for the treatment of orthopedic conditions.
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DOI:
10.1016/j.pharmthera.2016.08.003
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发表时间:
2017-03
影响因子:
13.5
通讯作者:
Soo C
Soo C
中科院分区:
医学1区
文献类型:
--
作者:
James AW;Hindle P;Murray IR;West CC;Tawonsawatruk T;Shen J;Asatrian G;Zhang X;Nguyen V;Simpson AH;Ting K;Péault B;Soo C

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周细胞和其他血管周围干细胞在骨科和组织工程中越来越受到关注。长期以来,周细胞被认为是血管生成和血压的简单调节因子,现在被认为具有 MSC(间充质干细胞)特征,包括多潜能、自我更新、免疫调节功能以及在组织修复中的多种作用。周细胞以特征性细胞表面标志物表达为代表(包括 αSMA、CD146、PDGFRβ、NG2、RGS5 等)。虽然没有单独的标记物对周细胞具有绝对特异性,但这些标记物总的来说似乎可以选择性地识别 MSC 样周细胞。周细胞的纯化最清楚地描述为 CD146+CD34−CD45− 细胞群。周细胞和其他血管周围干细胞群已应用于多种骨科应用,包括异位和原位模型。在啮齿动物模型中,纯化细胞的应用加速了颅骨修复、诱导脊柱融合并防止纤维不愈合。周细胞通过直接和间接机制诱导这些效应。就其旁分泌作用而言,已知周细胞在体外和移植后都会产生和分泌高水平的多种生长和分化因子。以下综述将涵盖迄今为止有关周细胞在骨和软骨工程中的应用的现有研究。此外,还将思考该领域的进一步问题,包括周细胞和培养源性 MSC 之间的表型和功能重叠,以及周细胞作为分化因子的有效产生者以加速组织修复的概念。
Pericytes and other perivascular stem cells are of growing interest in orthopedics and tissue engineering. Long regarded as simple regulators of angiogenesis and blood pressure, pericytes are now recognized to have MSC (mesenchymal stem cell) characteristics, including multipotentiality, self-renewal, immunoregulatory functions, and diverse roles in tissue repair. Pericytes are typified by characteristic cell surface marker expression (including αSMA, CD146, PDGFRβ, NG2, RGS5, among others). Although alone no marker is absolutely specific for pericytes, collectively these markers appear to selectively identify an MSC-like pericyte. The purification of pericytes is most well described as a CD146+CD34−CD45− cell population. Pericytes and other perivascular stem cell populations have been applied in diverse orthopedic applications, including both ectopic and orthotopic models. Application of purified cells has sped calvarial repair, induced spine fusion, and prevented fibrous non-union in rodent models. Pericytes induce these effects via both direct and indirect mechanisms. In terms of their paracrine effects, pericytes are known to produce and secrete high levels of a number of growth and differentiation factors both in vitro and after transplantation. The following review will cover existing studies to date regarding pericyte application for bone and cartilage engineering. In addition, further questions in the field will be pondered, including the phenotypic and functional overlap between pericytes and culture-derived MSC, and the concept of pericytes as efficient producers of differentiation factors to speed tissue repair.
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