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评估同种异体骨髓来源和脐带血来源的间充质干细胞在马模型中预防骨关节炎发展的效果。

Evaluation of Allogeneic Bone-Marrow-Derived and Umbilical Cord Blood-Derived Mesenchymal Stem Cells to Prevent the Development of Osteoarthritis in An Equine Model.

作者信息

Bertoni Lélia, Jacquet-Guibon Sandrine, Branly Thomas, Desancé Mélanie, Legendre Florence, Melin Martine, Rivory Pascaline, Hartmann Daniel-Jean, Schmutz Amandine, Denoix Jean-Marie, Demoor Magali, Audigié Fabrice, Galéra Philippe

机构信息

Center of Imaging and Research on Locomotor Affections on Equines (CIRALE), Unit Under Contract 957 Equine Biomechanics and Locomotor Disorders (USC 957 BPLC), French National Research Institute for Agriculture Food and Environment (INRAE), Ecole Nationale Vétérinaire d'Alfort, F-94700 Maisons-Alfort, France.

BIOTARGEN, UNICAEN, Normandie Université, 14000 Caen, France.

出版信息

Int J Mol Sci. 2021 Mar 2;22(5):2499. doi: 10.3390/ijms22052499.

DOI:10.3390/ijms22052499
PMID:33801461
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7958841/
Abstract

Osteoarthritis (OA) is a significant cause of pain in both humans and horses with a high socio-economic impact. The horse is recognized as a pertinent model for human OA. In both species, regenerative therapy with allogeneic mesenchymal stem cells (MSCs) appears to be a promising treatment but, to date, no in vivo studies have attempted to compare the effects of different cell sources on the same individuals. The objective of this study is to evaluate the ability of a single blinded intra-articular injection of allogeneic bone-marrow (BM) derived MSCs and umbilical cord blood (UCB) derived MSC to limit the development of OA-associated pathological changes compared to placebo in a post-traumatic OA model applied to all four fetlock joints of eight horses. The effect of the tissue source (BM vs. UCB) is also assessed on the same individuals. Observations were carried out using clinical, radiographic, ultrasonographic, and magnetic resonance imaging methods as well as biochemical analysis of synovial fluid and postmortem microscopic and macroscopic evaluations of the joints until Week 12. A significant reduction in the progression of OA-associated changes measured with imaging techniques, especially radiography, was observed after injection of bone-marrow derived mesenchymal stem cells (BM-MSCs) compared to contralateral placebo injections. These results indicate that allogeneic BM-MSCs are a promising treatment for OA in horses and reinforce the importance of continuing research to validate these results and find innovative strategies that will optimize the therapeutic potential of these cells. However, they should be considered with caution given the low number of units per group.

摘要

骨关节炎(OA)是导致人类和马匹疼痛的重要原因,具有很高的社会经济影响。马被认为是人类OA的相关模型。在这两个物种中,同种异体间充质干细胞(MSCs)的再生疗法似乎是一种有前景的治疗方法,但迄今为止,尚无体内研究试图比较不同细胞来源对同一动物个体的影响。本研究的目的是评估在应用于八匹马的四个跗关节的创伤后OA模型中,与安慰剂相比,单次盲法关节内注射同种异体骨髓(BM)来源的MSCs和脐带血(UCB)来源的MSCs限制OA相关病理变化发展的能力。还在同一动物个体上评估了组织来源(BM与UCB)的影响。使用临床、放射学、超声学和磁共振成像方法以及滑液的生化分析和关节的死后微观和宏观评估进行观察,直至第12周。与对侧安慰剂注射相比,注射骨髓来源的间充质干细胞(BM-MSCs)后,用成像技术尤其是放射学测量的OA相关变化的进展显著降低。这些结果表明,同种异体BM-MSCs是治疗马OA的一种有前景的方法,并强化了继续开展研究以验证这些结果并找到优化这些细胞治疗潜力的创新策略的重要性。然而,鉴于每组的单位数量较少,应谨慎考虑这些结果。

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