Chen You-Rong, Yan Xin, Yuan Fu-Zhen, Ye Jing, Xu Bing-Bing, Zhou Zhu-Xing, Mao Zi-Mu, Guan Jian, Song Yi-Fan, Sun Ze-Wen, Wang Xin-Jie, Chen Ze-Yi, Wang Ding-Yu, Fan Bao-Shi, Yang Meng, Song Shi-Tang, Jiang Dong, Yu Jia-Kuo
Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China.
School of Clinical Medicine, Weifang Medical University, Weifang, China.
Front Pharmacol. 2020 Apr 3;11:404. doi: 10.3389/fphar.2020.00404. eCollection 2020.
Peripheral blood (PB) is a potential source of chondrogenic progenitor cells that can be used for cartilage repair and regeneration. However, the cell types, isolation and implantation methods, seeding dosage, ultimate therapeutic effect, and safety remain unclear.
PubMed, Embase, and the Web of Science databases were systematically searched for relevant reports published from January 1990 to December 2019. Original articles that used PB as a source of stem cells to repair cartilage were selected for analysis.
A total of 18 studies were included. Eight human studies used autologous nonculture-expanded PB-derived stem cells (PBSCs) as seed cells with the blood cell separation isolation method, and 10 animal studies used autologous, allogenic or xenogeneic culture-expanded PB-derived mesenchymal stem cells (PB-MSCs), or nonculture-expanded PBSCs as seed cells. Four human and three animal studies surgically implanted cells, while the remaining studies implanted cells by single or repeated intra-articular injections. 121 of 130 patients (in 8 human clinical studies), and 230 of 278 animals (in 6 veterinary clinical studies) using PBSCs for cartilage repair achieved significant clinical improvement. All reviewed articles indicated that using PB as a source of seed cells enhances cartilage repair without serious adverse events.
Autologous nonculture-expanded PBSCs are currently the most commonly used cells among all stem cell types derived from PB. Allogeneic, autologous, and xenogeneic PB-MSCs are more widely used in animal studies and are potential seed cell types for future applications. Improving the mobilization and purification technology, and shortening the culture cycle of culture-expanded PB-MSCs will obviously promote the researchers' interest. The use of PBSCs for cartilage repair and regeneration are safe. PBSCs considerably warrant further investigations due to their superiority and safety in clinical settings and positive effects despite limited evidence in humans.
外周血（PB）是软骨形成祖细胞的一个潜在来源，可用于软骨修复和再生。然而，细胞类型、分离和植入方法、接种剂量、最终治疗效果及安全性仍不明确。
系统检索PubMed、Embase和Web of Science数据库中1990年1月至2019年12月发表的相关报告。选取以PB作为干细胞来源修复软骨的原始文章进行分析。
共纳入18项研究。8项人体研究使用自体非培养扩增的PB来源干细胞（PBSCs）作为种子细胞，采用血细胞分离法进行分离；10项动物研究使用自体、异体或异种培养扩增的PB来源间充质干细胞（PB-MSCs）或非培养扩增的PBSCs作为种子细胞。4项人体研究和3项动物研究通过手术植入细胞，其余研究通过单次或反复关节内注射植入细胞。在8项人体临床研究中，130例患者中有121例使用PBSCs进行软骨修复取得了显著的临床改善；在6项兽医临床研究中，278只动物中有230只取得了显著改善。所有纳入综述的文章均表明，使用PB作为种子细胞来源可增强软骨修复，且无严重不良事件发生。
自体非培养扩增的PBSCs是目前PB来源的所有干细胞类型中最常用的细胞。异体、自体和异种PB-MSCs在动物研究中应用更为广泛，是未来潜在的种子细胞类型。改进动员和纯化技术，缩短培养扩增PB-MSCs的培养周期将显著提高研究人员的兴趣。使用PBSCs进行软骨修复和再生是安全的。尽管在人体中的证据有限，但PBSCs因其在临床环境中的优势、安全性和积极效果，非常值得进一步研究。
