Integrin α10β1-Selected Mesenchymal Stem Cells Reduce Pain and Cartilage Degradation and Increase Immunomodulation in an Equine Osteoarthritis Model.

IF 2.7 4区 医学 Q1 ORTHOPEDICS
CARTILAGE Pub Date : 2025-06-01 Epub Date: 2023-11-21 DOI:10.1177/19476035231209402
Camilla Andersen, Stine Jacobsen, Kristina Uvebrant, John F Griffin, Lucienne Angela Vonk, Marie Walters, Lise Charlotte Berg, Evy Lundgren-Åkerlund, Casper Lindegaard
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引用次数: 0

Abstract

ObjectiveIntegrin α10β1-selected mesenchymal stem cells (integrin α10-MSCs) have previously shown potential in treating cartilage damage and osteoarthritis (OA) in vitro and in animal models in vivo. The aim of this study was to further investigate disease-modifying effects of integrin α10-MSCs.DesignOA was surgically induced in 17 horses. Eighteen days after surgery, horses received 2 × 107 integrin α10-MSCs intra-articularly or were left untreated. Lameness and response to carpal flexion was assessed weekly along with synovial fluid (SF) analysis. On day 52 after treatment, horses were euthanized, and carpi were evaluated by computed tomography (CT), MRI, histology, and for macroscopic pathology and integrin α10-MSCs were traced in the joint tissues.ResultsLameness and response to carpal flexion significantly improved over time following integrin α10-MSC treatment. Treated horses had milder macroscopic cartilage pathology and lower cartilage histology scores than the untreated group. Prostaglandin E2 and interleukin-10 increased in the SF after integrin α10-MSC injection. Integrin α10-MSCs were found in SF from treated horses up to day 17 after treatment, and in the articular cartilage and subchondral bone from 5 of 8 treated horses after euthanasia at 52 days after treatment. The integrin α10-MSC injection did not cause joint flare.ConclusionThis study demonstrates that intra-articular (IA) injection of integrin α10-MSCs appears to be safe, alleviate pathological changes in the joint, and improve joint function in an equine post-traumatic osteoarthritis (PTOA) model. The results suggest that integrin α10-MSCs hold promise as a disease-modifying osteoarthritis drug (DMOAD).

整合素α10β1-选择间充质干细胞在马骨关节炎模型中减轻疼痛和软骨退化并增加免疫调节。
目的:整合素α10β1选择间充质干细胞(Integrin α10-MSCs)先前在体外和体内动物模型中显示出治疗软骨损伤和骨关节炎(OA)的潜力。本研究旨在进一步探讨整合素α - 10- mscs的疾病调节作用。设计:17匹马手术诱导OA。术后18天,马关节内注射2 × 107整合素α - 10- mscs或不给予治疗。跛行和对腕屈曲的反应每周进行评估,并进行滑液(SF)分析。治疗后第52天对马实施安乐死,采用CT、MRI、组织学和宏观病理学对其腕关节进行评估,并在关节组织中追踪整合素α - 10- mscs。结果:整合素α10-MSC治疗后,跛行和腕屈曲反应随时间的推移显着改善。与未治疗组相比,治疗组的肉眼软骨病理较轻,软骨组织学评分较低。注射整合素α10-MSC后SF中前列腺素E2和白细胞介素10升高。整联素α10-MSCs存在于治疗后第17天的治疗马的SF中,在治疗后52天安乐死后8匹治疗马中有5匹的关节软骨和软骨下骨中。注射整合素α10-MSC未引起关节耀斑。结论:本研究表明,在马创伤后骨关节炎(PTOA)模型中,关节内注射整合素α10-MSCs是安全的,可以减轻关节的病理改变,改善关节功能。结果表明,整合素α - 10- mscs有望成为一种疾病改善性骨关节炎药物。
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来源期刊
CARTILAGE
CARTILAGE ORTHOPEDICS-
CiteScore
6.90
自引率
7.10%
发文量
80
期刊介绍: CARTILAGE publishes articles related to the musculoskeletal system with particular attention to cartilage repair, development, function, degeneration, transplantation, and rehabilitation. The journal is a forum for the exchange of ideas for the many types of researchers and clinicians involved in cartilage biology and repair. A primary objective of CARTILAGE is to foster the cross-fertilization of the findings between clinical and basic sciences throughout the various disciplines involved in cartilage repair. The journal publishes full length original manuscripts on all types of cartilage including articular, nasal, auricular, tracheal/bronchial, and intervertebral disc fibrocartilage. Manuscripts on clinical and laboratory research are welcome. Review articles, editorials, and letters are also encouraged. The ICRS envisages CARTILAGE as a forum for the exchange of knowledge among clinicians, scientists, patients, and researchers. The International Cartilage Repair Society (ICRS) is dedicated to promotion, encouragement, and distribution of fundamental and applied research of cartilage in order to permit a better knowledge of function and dysfunction of articular cartilage and its repair.
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