Lee Sang Yoon, Kwon Bomi, Lee Kyoungbun, Son Young Hoon, Chung Sun G
Department of Physical Medicine & Rehabilitation, Chung-Ang University College of Medicine, Seoul, South Korea.
Department of Rehabilitation Medicine, Seoul National University Boramae Medical Center, Seoul, South Korea.
Am J Sports Med. 2017 May;45(6):1429-1439. doi: 10.1177/0363546517689874. Epub 2017 Mar 14.
Although survival of transplanted stem cells in vivo and differentiation of stem cells into tenocytes in vitro have been reported, there have been no in vivo studies demonstrating that mesenchymal stem cells (MSCs) could secrete their own proteins as differentiated tenogenic cells. Purpose/Hypothesis: Using a xenogeneic MSC transplantation model, we aimed to investigate whether MSCs could differentiate into the tenogenic lineage and secrete their own proteins. The hypothesis was that human MSCs would differentiate into the human tenogenic lineage and the cells would be able to secrete human-specific proteins in a rat tendon injury model.
Controlled laboratory study.
The Achilles tendons of 57 Sprague Dawley rats received full-thickness rectangular defects. After the modeling, the defective tendons were randomly assigned to 3 groups: (1) cell group, implantation with human adipose-derived mesenchymal stem cells (hASCs) and fibrin glue (10 cells in 60 μL); (2) fibrin group, implantation with fibrin glue and same volume of cell media; and (3) sham group, identical surgical procedure without any treatment. Gross observation and biomechanical, histopathological, immunohistochemistry, and Western blot analyses were performed at 2 and 4 weeks after modeling.
hASCs implanted into the defective rat tendons were viable for 4 weeks as detected by immunofluorescence staining. Tendons treated with hASCs showed better gross morphological and biomechanical recovery than those in the fibrin and sham groups. Furthermore, the expression of both human-specific collagen type I and tenascin-C was significantly higher in the cell group than in the other 2 groups.
Transplantation of hASCs enhanced rat tendon healing biomechanically. hASCs implanted into the rat tendon defect model survived for at least 4 weeks and secreted human-specific collagen type I and tenascin-C. These findings suggest that transplanted MSCs may be able to differentiate into the tenogenic lineage and contribute their own proteins to tendon healing.
In tendon injury, MSCs can enhance tendon healing by secreting their own protein and have potential as a therapeutic option in human tendinopathy.
尽管已有报道称移植的干细胞在体内存活以及干细胞在体外分化为肌腱细胞，但尚无体内研究表明间充质干细胞（MSCs）能够作为分化的肌腱生成细胞分泌自身蛋白质。目的/假设：使用异种 MSC 移植模型，我们旨在研究 MSCs 是否能够分化为肌腱生成谱系并分泌自身蛋白质。假设是在大鼠肌腱损伤模型中，人 MSCs 将分化为人肌腱生成谱系，并且这些细胞能够分泌人特异性蛋白质。
对照实验室研究。
57 只 Sprague Dawley 大鼠的跟腱接受全层矩形缺损。建模后，将缺损的肌腱随机分为 3 组：（1）细胞组，植入人脂肪来源的间充质干细胞（hASCs）和纤维蛋白胶（60 μL 中含 10 个细胞）；（2）纤维蛋白组，植入纤维蛋白胶和相同体积的细胞培养基；（3）假手术组，进行相同的手术操作但不进行任何治疗。在建模后 2 周和 4 周进行大体观察、生物力学、组织病理学、免疫组织化学和蛋白质印迹分析。
通过免疫荧光染色检测，植入缺损大鼠肌腱中的 hASCs 在 4 周内均存活。与纤维蛋白组和假手术组相比，用 hASCs 处理的肌腱在大体形态和生物力学恢复方面表现更好。此外，细胞组中人特异性 I 型胶原蛋白和肌腱蛋白 -C 的表达均显著高于其他两组。
hASCs 移植在生物力学上增强了大鼠肌腱愈合。植入大鼠肌腱缺损模型中的 hASCs 存活至少 4 周，并分泌人特异性 I 型胶原蛋白和肌腱蛋白 -C。这些发现表明，移植的 MSCs 可能能够分化为肌腱生成谱系，并为肌腱愈合贡献自身蛋白质。
在肌腱损伤中，MSCs 可通过分泌自身蛋白质增强肌腱愈合，在人类肌腱病中具有作为治疗选择的潜力。
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