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通过关节腔内移植循环间充质干细胞缓解骨关节炎

Alleviation of osteoarthritis by intra-articular transplantation of circulating mesenchymal stem cells.

作者信息

Lin Weiping, Yang Zhengmeng, Shi Liu, Wang Haixing, Pan Qi, Zhang Xiaoting, Zhang Peng, Lin Sien, Li Gang

机构信息

Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, PR China; Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, PR China.

Institute of Translational and Medical Research and Development Center, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China.

出版信息

Biochem Biophys Res Commun. 2022 Dec 25;636(Pt 1):25-32. doi: 10.1016/j.bbrc.2022.10.064. Epub 2022 Oct 21.

Abstract

This study aimed to evaluate the efficacy of intra-articular delivery of peripheral blood derived mesenchymal stromal cells (PB-MSCs) on the progression of trauma-induced osteoarthritis (OA) in mice. Adult male C57BL/6J mice subjected to destabilization of the medial meniscus surgeries (DMM) were randomly divided into four groups: sham surgery group; vehicle control group (treated with saline), PBMSC-treated group, or adipose tissue derived MSCs (AD-MSC)-treated group (n = 4 per group). PB-MSCs and AD-MSCs were harvested and cultured following previously established protocols, and pre-labeled with BrdU for 48 h before transplantation. PB-MSCs or AD-MSCs (5 × 10 cells/mouse; passage 3-5) were intra-articular injected into the right knee joints thrice post-surgery. The mice were euthanized at 8 weeks post-surgery and knee joint samples were collected for micro-CT and histological examinations. PB-MSCs administration significantly reduced subchondral bone volume comparing to the vehicle control group. Safranin O staining showed that PB-MSCs treatment ameliorated degeneration of articular cartilage, which was comparable to AD-MSCs treatment. The expression of catabolic marker MMP13 was significantly reduced in articular cartilage of the PB-MSCs treated group comparing to that of the vehicle control group. Co-expression of BrdU and Sox9 indicated that injected PB-MSCs differentiated in chondrocytes in situ, along with reduced levels of IL-6 within peripheral sera of PB-MSCs- and AD-MSCs-treated mice. Therefore, administration of PB-MSCs or AD-MSCs attenuated trauma-induced OA progression through inhibiting cartilage degradation and inflammation. PB-MSCs are ideal cell source for treating cartilage-associated diseases.

摘要

本研究旨在评估关节腔内注射外周血源性间充质基质细胞(PB-MSCs)对小鼠创伤性骨关节炎(OA)进展的疗效。成年雄性C57BL/6J小鼠接受内侧半月板不稳定手术(DMM)后,随机分为四组:假手术组;载体对照组(用生理盐水处理)、PBMSC处理组或脂肪组织源性间充质干细胞(AD-MSC)处理组(每组n = 4)。按照先前建立的方案收获并培养PB-MSCs和AD-MSCs,并在移植前用BrdU预标记48小时。术后三次将PB-MSCs或AD-MSCs(5×10个细胞/小鼠;传代3-5)关节腔内注射到右膝关节。在术后8周对小鼠实施安乐死,并收集膝关节样本进行显微CT和组织学检查。与载体对照组相比,PB-MSCs给药显著降低了软骨下骨体积。番红O染色显示,PB-MSCs治疗改善了关节软骨退变,与AD-MSCs治疗相当。与载体对照组相比,PB-MSCs处理组关节软骨中分解代谢标志物MMP13的表达显著降低。BrdU和Sox9的共表达表明,注射的PB-MSCs在原位分化为软骨细胞,同时PB-MSCs和AD-MSCs处理的小鼠外周血清中IL-6水平降低。因此,PB-MSCs或AD-MSCs的给药通过抑制软骨降解和炎症减轻了创伤性OA的进展。PB-MSCs是治疗软骨相关疾病的理想细胞来源。

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