Burk Janina, Plenge Amelie, Brehm Walter, Heller Sandra, Pfeiffer Bastian, Kasper Cornelia
Translational Centre for Regenerative Medicine, University of Leipzig, Philipp-Rosenthal-Strasse 55, 04103 Leipzig, Germany; Saxon Incubator for Clinical Translation, University of Leipzig, Philipp-Rosenthal-Strasse 55, 04103 Leipzig, Germany; Institute of Veterinary Physiology, University of Leipzig, An den Tierkliniken 7, 04103 Leipzig, Germany.
Large Animal Clinic for Surgery, University of Leipzig, An den Tierkliniken 21, 04103 Leipzig, Germany.
Stem Cells Int. 2016;2016:7342379. doi: 10.1155/2016/7342379. Epub 2016 Aug 18.
Tendon and ligament pathologies are still a therapeutic challenge, due to the difficulty in restoring the complex extracellular matrix architecture and biomechanical strength. While progress is being made in cell-based therapies and tissue engineering approaches, comprehensive understanding of the fate of progenitor cells in tendon healing is still lacking. The aim of this study was to investigate the effect of decellularized tendon matrix and moderate cyclic stretching as natural stimuli which could potentially direct tenogenic fate. Equine adipose-derived mesenchymal stromal cells (MSC) were seeded on decellularized tendon matrix scaffolds. Mechanical stimulation was applied in a custom-made cyclic strain bioreactor. Assessment was performed 4 h, 8 h, and 24 h following mechanical stimulation. Scaffold culture induced cell alignment and changes in expression of tendon-related genes, although cell viability was decreased compared to monolayer culture. Short mechanical stimulation periods enhanced most of the scaffold-induced effects. Collagen 1A2 expression levels were decreased, while collagen 3A1 and decorin levels were increased. Tenascin-C and scleraxis expression showed an initial decrease but had increased 24 h after stimulation. The results obtained suggest that decellularized tendon matrix, supported by cyclic stretching, can induce tenogenic differentiation and the synthesis of tendon components important for matrix remodeling.
由于难以恢复复杂的细胞外基质结构和生物力学强度，肌腱和韧带病变仍然是一个治疗挑战。虽然基于细胞的疗法和组织工程方法正在取得进展，但对肌腱愈合过程中祖细胞命运的全面了解仍然不足。本研究的目的是研究脱细胞肌腱基质和适度循环拉伸作为可能引导肌腱形成命运的天然刺激因素的作用。将马脂肪来源的间充质基质细胞（MSC）接种在脱细胞肌腱基质支架上。在定制的循环应变生物反应器中施加机械刺激。在机械刺激后4小时、8小时和24小时进行评估。支架培养诱导细胞排列以及肌腱相关基因表达的变化，尽管与单层培养相比细胞活力有所下降。短时间的机械刺激增强了大多数支架诱导的效应。胶原蛋白1A2表达水平降低，而胶原蛋白3A1和核心蛋白聚糖水平升高。肌腱蛋白-C和硬骨素表达最初下降，但在刺激后24小时有所增加。获得的结果表明，在循环拉伸的支持下，脱细胞肌腱基质可以诱导肌腱形成分化以及对基质重塑重要的肌腱成分的合成。
