Yun Young-Joo, Kim Yeasol, Kim Tae Woo, Bae Kee Jeong, Jo Chris Hyunchul
Department of Orthopedic Surgery, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Stem Cells Int. 2025 Jul 10;2025:8681205. doi: 10.1155/sci/8681205. eCollection 2025.
Aging, linked to reduced tendon healing and higher injury susceptibility, is associated to the high incidence of rotator cuff (RC) tears in the elderly. Even after RC repair, disordered neofibrovascular scar tissue often occurs, lowering mechanical strength, and tendon-derived cell (TDC) senescence has been suggested as one of the causes. Age reduces the efficacy of mesenchymal stem cell (MSC) therapy for tendon regeneration. However, certain biomaterial exposure may increase MSC differentiation and paracrine effects. We aimed to develop and evaluate an optimal tenon-MSC complex (TSC) for tendon regeneration and investigate its efficacy and antisenescence mechanisms in aged and degenerated TDCs. We proposed a novel method to isolate a maximum quantity of tenon with col6-rich pericellular matrix (PCM) per gram of tendon, utilizing 2% collagenase. In a fibrin 3D gel culture system, rejuvenated METn (TSC) had higher tenogenic marker expression, collagen fiber quantity, and quality than MSC-only or METc (TDC-MSC complex). METn could repair DNA damage and improve cellular metabolism in senescent TDCs by releasing antisenescence factors. TDCs, which overcomes senescence by the METn_CM treatment, also produced a higher quality tendon matrix. In conclusion, this study demonstrates that rejuvenated and functional TSC significantly enhances tendon regeneration by countering senescence in aged and degenerated TDCs, offering a safe approach to enhance the therapeutic potential of autologous senescent MSCs from the elderly.
衰老与肌腱愈合能力下降和更高的损伤易感性相关，这与老年人肩袖（RC）撕裂的高发生率有关。即使在RC修复后，也经常会出现紊乱的新生血管瘢痕组织，降低机械强度，并且肌腱来源细胞（TDC）衰老被认为是原因之一。年龄会降低间充质干细胞（MSC）治疗肌腱再生的效果。然而，某些生物材料暴露可能会增加MSC的分化和旁分泌作用。我们旨在开发和评估一种用于肌腱再生的最佳腱-MSC复合物（TSC），并研究其在衰老和退变的TDC中的功效和抗衰老机制。我们提出了一种新方法，利用2%的胶原酶从每克肌腱中分离出最大量的富含胶原蛋白6的细胞周基质（PCM）的腱。在纤维蛋白3D凝胶培养系统中，恢复活力的METn（TSC）比仅含MSC或METc（TDC-MSC复合物）具有更高的肌腱生成标记物表达、胶原纤维数量和质量。METn可以通过释放抗衰老因子来修复衰老TDC中的DNA损伤并改善细胞代谢。通过METn_CM处理克服衰老的TDC也产生了更高质量的肌腱基质。总之，本研究表明，恢复活力且具有功能的TSC通过对抗衰老和退变的TDC中的衰老，显著增强了肌腱再生能力，为提高老年人自体衰老MSC的治疗潜力提供了一种安全的方法。
