Clinical outcomes of autologous adipose-derived mesenchymal stem cell combined with high tibial osteotomy for knee osteoarthritis are correlated with stem cell stemness and senescence

作者：Houyi Sun, Haoxin Zhai, Kaifei Han, Heran Ma, Yi Tan, Shihao Li, Zhicheng Liu, Lei Cheng, Qunshan Lu, Libo Zhou, Peilai Liu · 发表于：Journal of Translational Medicine · 年份：2024 · DOI：10.1186/s12967-024-05814-3 · 被引用次数：19 · 研究领域：Mesenchymal stem cell research、Osteoarthritis Treatment and Mechanisms、Periodontal Regeneration and Treatments

BACKGROUND: Mesenchymal stem cells (MSCs) have been proposed to treat osteoarthritis (OA) for many years. However, clinical outcomes have been inconsistent due to biological variation between patients, differences in tissue source and preparation of the MSCs, and type of donor (e.g. allogenic versus autologous). Here, we test the hypothesis that inconsistent clinical outcomes are related to variations in the stemness and senescence of the injected autologous adipose-derived (AD) MSCs. METHODS: In the prospective randomized trial, 45 knee OA patients were divided into two groups: Group 1 (n = 22) patients treated with high tibial osteotomy (HTO) alone and Group 2 (n = 23) patients treated with HTO followed by intra-articular injection of autologous AD-MSCs (HTO + AD-MSCs). MRI and X-ray were performed pre-operation and 12 months post-operation. WOMAC and VAS score were collected four times, every 6 months over a 24-month follow-up. We observed the proliferation and stemness of AD-MSCs selected from the 5 patients showing the most improvement and from the 5 patients with the least improvement, and completed further in vitro experiments including beta-galactosidase activity, reactive oxygen species and bioinformatic analysis. RESULTS: The results showed that patients treated with HTO + AD-MSCs had a significant reduction in knee OA severity as compared to patients treated with HTO alone. Moreover, we discovered that proliferation and colony forming efficiency of AD-MSCs selected...