Komatsu Issei, Wang James H-C, Iwasaki Kiyotaka, Shimizu Tatsuya, Okano Teruo
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada, Shinjuku, Tokyo 162-8480, Japan; MechanoBioblogy Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 210 Lothrop Street, Pittsburgh, PA 15213, United States.
MechanoBioblogy Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 210 Lothrop Street, Pittsburgh, PA 15213, United States.
Acta Biomater. 2016 Sep 15;42:136-146. doi: 10.1016/j.actbio.2016.06.026. Epub 2016 Jun 18.
Tissue-engineering approaches have a great potential to improve the treatment of tendon injuries that affect millions of people. The present study tested the hypothesis that introduction of a tendon derived stem/progenitor cell (TSC) sheet accelerates tendon healing and tendon regeneration in a rat model. TSC sheets were produced on temperature-responsive culture dishes. Then, they were grafted on unwounded Achilles tendons and at sites of a 3mm of Achilles tendon defect. At 2 and 4weeks after implantation tendons were examined by histology, immunohistochemistry, transmission electron microscopy (TEM) and mechanical testing. The results showed that the implanted TSC sheet remained stably attached on the tendon surface at 4 weeks after implantation. Moreover, in the tendon defect model, tendon defect area where TSC sheet was implanted was well regenerated and had better organized collagen fibers with elongated spindle shaped cells, compared to relatively disorganized collagen fibers and round shaped cells in the control group. TEM observations revealed longitudinally aligned collagen fibers and thick collagen fibrils in the TSC sheet implanted group. Finally, at 4weeks mechanical property of the TSC sheet implanted tendon had better ultimate load than the control. In conclusion, this study demonstrates the feasibility of implanting TSC sheets on tendons in vivo. Introduction of the cell sheets into a tendon defect significantly improved histological properties and collagen content at both 2 and 4 weeks after implantation, indicating that TSC sheets may effectively promote tendon remodeling in the early stages of tendon healing.
Tendon injury is a highly prevalent clinical problem that debilitates millions of people worldwide in both occupational and athletic settings. It also costs billions of healthcare dollars in treatment every year. In this study, we showed the feasibility of using tendon derived stem cell sheet to deliver biologically active tenogenic-constructs and promote tendon regeneration. This work has the potential to impact the orthopaedic surgery and sports medicine fields in the treatment of tendon injury.
组织工程方法在改善影响数百万人的肌腱损伤治疗方面具有巨大潜力。本研究验证了以下假设:引入肌腱来源的干/祖细胞(TSC)片可加速大鼠模型中的肌腱愈合和再生。TSC片在温度响应培养皿上制备。然后,将它们移植到未受伤的跟腱上以及3毫米跟腱缺损部位。在植入后2周和4周,通过组织学、免疫组织化学、透射电子显微镜(TEM)和力学测试对肌腱进行检查。结果表明,植入的TSC片在植入后4周时稳定附着在肌腱表面。此外,在肌腱缺损模型中,与对照组中相对紊乱的胶原纤维和圆形细胞相比,植入TSC片的肌腱缺损区域得到良好再生,胶原纤维排列更有序,细胞呈细长纺锤形。TEM观察显示,植入TSC片的组中胶原纤维纵向排列且胶原原纤维较粗。最后,在4周时,植入TSC片的肌腱的力学性能比对照组具有更好的极限负荷。总之,本研究证明了在体内将TSC片植入肌腱的可行性。将细胞片引入肌腱缺损在植入后2周和4周均显著改善了组织学特性和胶原含量,表明TSC片可有效促进肌腱愈合早期的肌腱重塑。
肌腱损伤是一个高度普遍的临床问题,在职业和运动环境中使全球数百万人衰弱。每年治疗肌腱损伤的医疗费用也高达数十亿美元。在本研究中,我们展示了使用肌腱来源的干细胞片递送具有生物活性的成腱构建体并促进肌腱再生的可行性。这项工作有可能在肌腱损伤的治疗中影响骨科手术和运动医学领域。