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Regeneration of a full-thickness defect of rotator cuff tendon with freshly thawed umbilical cord-derived mesenchymal stem cells in a rat model.
Stem Cell Research & Therapy ( IF 7.5 ) Pub Date : 2020-09-07 , DOI: 10.1186/s13287-020-01906-1
Ji-Hye Yea 1, 2 , Jin-Kyung Park 2 , In Ja Kim 2 , Gayoung Sym 2 , Tae-Soo Bae 3 , Chris Hyunchul Jo 1, 2
Affiliation  

It is difficult to immediately use mesenchymal stem cells (MSCs) for the patient with rotator cuff disease because isolation and culture time are required. Thus, the MSCs would be prepared in advanced in cryopreserved condition for an “off-the-shelf” usage in clinic. This study investigated the efficacy of freshly thawed MSCs on the regeneration of a full-thickness tendon defect (FTD) of rotator cuff tendon in a rat model. We evaluated morphology, viability, and proliferation of cultured umbilical cord-derived MSCs (C-UC MSCs) and freshly thawed umbilical cord-derived MSCs (T-UC MSCs) at passage 10 in vitro. In animal experiments, we created a FTD in the supraspinatus of rats and injected the injured tendon with saline, cryopreserved agent (CPA; control), C-UC MSCs, and T-UC MSCs, respectively. Two and 4 weeks later, macroscopic, histological, biomechanical, and cell trafficking were evaluated. T test and ANOVA were used with SPSS. Differences with p < .05 were considered statistically significant. T-UC MSCs had fibroblast-like morphology and showed greater than 97% viability and stable proliferation comparable to the C-UC MSCs at passage 10. In animal experiments, compared with the control group, the macroscopic appearance of the T-UC MSCs was more recovered at 2 and 4 weeks such as inflammation, defect size, neighboring tendon, swelling/redness, the connecting surrounding tissue and slidability. Histologically, the nuclear aspect ratio, orientation angle of fibroblasts, collagen organization, and fiber coherence were improved by 33.33%, 42.75%, 1.86-fold, and 1.99-fold at 4 weeks, and GAG-rich area decreased by 88.13% and 94.70% at 2 and 4 weeks respectively. Further, the T-UC MSCs showed enhanced ultimate failure load by 1.55- and 1.25-fold compared with the control group at both 2 and 4 weeks. All the improved values of T-UC MSCs were comparable to those of C-UC MSCs. Moreover, T-UC MSCs remained 8.77% at 4 weeks after injury, and there was no significant difference between C-UC MSCs and T-UC MSCs. The morphology, viability, and proliferation of T-UC MSCs were comparable to those of C-UC MSCs. Treatment with T-UC MSCs could induce tendon regeneration of FTD at the macroscopic, histological, and biomechanical levels comparable to treatment with C-UC MSCs.

中文翻译:

大鼠模型中新鲜融化的脐带间充质干细胞对肩袖腱全层缺损的再生。

对于患有肩袖疾病的患者,很难立即使用间充质干细胞(MSC),因为需要隔离和培养时间。因此,将在冷冻保存条件下提前准备MSC,以在临床中“现成”使用。这项研究调查了新鲜融化的MSC对大鼠模型中袖套肌腱全层肌腱缺损(FTD)再生的功效。我们评估了第10代体外培养的脐带来源的MSC(C-UC MSC)和新鲜融化的脐带来源的MSC(T-UC MSC)的形态,活力和增殖。在动物实验中,我们在大鼠上棘上创建了一个FTD,并分别向受伤的肌腱注射生理盐水,冷冻保存剂(CPA;对照),C-UC MSC和T-UC MSC。2和4周后,从宏观,组织学,生物力学和细胞运输进行了评估。T检验和方差分析与SPSS一起使用。p <.05的差异被认为具有统计学意义。T-UC MSC具有成纤维细胞样的形态,并在第10代时具有与C-UC MSC相当的97%的活力和稳定的增殖。在动物实验中,与对照组相比,T-UC MSC的宏观外观为在第2和第4周恢复更多,例如炎症,缺损大小,邻近肌腱,肿胀/发红,周围的连接组织和滑动性。从组织学上看,在第4周时,核长宽比,成纤维细胞的定向角,胶原组织和纤维凝聚力分别提高了33.33%,42.75%,1.86倍和1.99倍,富含GAG的面积减少了88.13%和94.70。 %分别在第2周和第4周。进一步,T-UC MSC在第2周和第4周时均显示出比对照组高的最终破坏载荷1.55倍和1.25倍。T-UC MSC的所有改进值均与C-UC MSC相当。此外,T-UC MSC在损伤后4周仍保持8.77%,并且C-UC MSC和T-UC MSC之间无显着差异。T-UC MSC的形态,活力和增殖与C-UC MSC相当。T-UC MSC的治疗可以在宏观,组织学和生物力学水平上诱导FTD的肌腱再生,与C-UC MSC的治疗相当。C-UC MSC和T-UC MSC之间无显着差异。T-UC MSC的形态,活力和增殖与C-UC MSC相当。T-UC MSC的治疗可以在宏观,组织学和生物力学水平上诱导FTD的肌腱再生,与C-UC MSC的治疗相当。C-UC MSC和T-UC MSC之间无显着差异。T-UC MSC的形态,活力和增殖与C-UC MSC相当。T-UC MSC的治疗可以在宏观,组织学和生物力学水平上诱导FTD的肌腱再生,与C-UC MSC的治疗相当。
更新日期:2020-09-08
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