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采用原弹性蛋白增强的自体基质血管成分凝胶进行骨关节炎的一步法基质血管成分治疗

One-step stromal vascular fraction therapy in osteoarthritis with tropoelastin-enhanced autologous stromal vascular fraction gel.

作者信息

Yang Junjun, Wang Xin, Zeng XueBao, Wang Rong, Ma Yanming, Fu Zhenlan, Wan Zu, Wang Zhi, Yang Liu, Chen Guangxing, Gong Xiaoyuan

机构信息

Center for Joint Surgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, China.

出版信息

Front Bioeng Biotechnol. 2024 Feb 12;12:1359212. doi: 10.3389/fbioe.2024.1359212. eCollection 2024.

Abstract

Osteoarthritis (OA) is a debilitating degenerative joint disease, leading to significant pain and disability. Despite advancements, current regenerative therapies, such as mesenchymal stem cells (MSCs), face challenges in clinical efficacy and ethical considerations. This study aimed to evaluate the therapeutic potential of stromal vascular fraction gel (SVF-gel) in comparison to available treatments like hyaluronic acid (HA) and adipose-derived stem cells (ADSCs) and to assess the enhancement of this potential by incorporating tropoelastin (TE). We conducted a comparative laboratory study, establishing an indirect co-culture system using a Transwell assay to test the effects of HA, ADSCs, SVF-gel, and TE-SVF-gel on osteoarthritic articular chondrocytes (OACs). Chondrogenic and hypertrophic markers were assessed after a 72-hour co-culture. SVF-gel was harvested from rat subcutaneous abdominal adipose tissue, with its mechanical properties characterized. Cell viability was specifically analyzed for SVF-gel and TE-SVF-gel. The therapeutic effectiveness was further investigated in a rat model of OA, examining MSCs tracking, effects on cartilage matrix synthesis, osteophyte formation, and muscle weight changes. Cell viability assays revealed that TE-SVF-gel maintained higher cell survival rates than SVF-gel. In comparison to the control, HA, and ADSCs groups, SVF-gel and TE-SVF-gel significantly upregulated the expression of chondrogenic markers COL 2, SOX-9, and ACAN and downregulated the hypertrophic marker COL 10 in OACs. The TE-SVF-gel showed further improved expression of chondrogenic markers and a greater decrease in COL 10 expression compared to SVF-gel alone. Notably, the TE-SVF-gel treated group in the OA model exhibited the most MSCs on the synovial surface, superior cartilage matrix synthesis, increased COL 2 expression, and better muscle weight recovery, despite the presence of fewer stem cells than other treatments. The findings suggest that SVF-gel, particularly when combined with TE, provides a more effective regenerative treatment for OA by enhancing the therapeutic potential of MSCs. This combination could represent an innovative strategy that overcomes limitations of current therapies, offering a new avenue for patient treatment. Further research is warranted to explore the long-term benefits and potential clinical applications of this combined approach.

摘要

骨关节炎(OA)是一种使人衰弱的退行性关节疾病,会导致严重疼痛和残疾。尽管取得了进展,但目前的再生疗法,如间充质干细胞(MSCs),在临床疗效和伦理考量方面仍面临挑战。本研究旨在评估基质血管成分凝胶(SVF - gel)与透明质酸(HA)和脂肪来源干细胞(ADSCs)等现有治疗方法相比的治疗潜力,并评估通过掺入原弹性蛋白(TE)对这种潜力的增强作用。我们进行了一项对比实验室研究,使用Transwell试验建立间接共培养系统,以测试HA、ADSCs、SVF - gel和TE - SVF - gel对骨关节炎关节软骨细胞(OACs)的影响。共培养72小时后评估软骨形成和肥大标志物。从大鼠腹部皮下脂肪组织中获取SVF - gel,并对其力学性能进行表征。专门分析了SVF - gel和TE - SVF - gel的细胞活力。在OA大鼠模型中进一步研究治疗效果,检查MSCs追踪情况、对软骨基质合成的影响、骨赘形成以及肌肉重量变化。细胞活力测定显示,TE - SVF - gel比SVF - gel维持更高的细胞存活率。与对照组、HA组和ADSCs组相比,SVF - gel和TE - SVF - gel显著上调OACs中软骨形成标志物COL 2、SOX - 9和ACAN的表达,并下调肥大标志物COL 10的表达。与单独的SVF - gel相比,TE - SVF - gel显示出软骨形成标志物表达的进一步改善和COL 10表达的更大降低。值得注意的是,尽管与其他治疗相比干细胞数量较少,但OA模型中TE - SVF - gel治疗组在滑膜表面显示出最多的MSCs、更好的软骨基质合成、COL 2表达增加以及更好的肌肉重量恢复。研究结果表明,SVF - gel,特别是与TE联合使用时,通过增强MSCs的治疗潜力为OA提供了更有效的再生治疗。这种联合可能代表一种创新策略,克服了当前疗法的局限性,为患者治疗提供了新途径。有必要进一步研究探索这种联合方法的长期益处和潜在临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3884/10895027/d5bc8d1a7c5f/fbioe-12-1359212-g001.jpg

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