Induction of Tenogenic Differentiation Mediated by Extracellular Tendon Matrix and Short-Term Cyclic Stretching.

Induction of Tenogenic Differentiation Mediated by Extracellular Tendon Matrix and Short-Term Cyclic Stretching.
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DOI:
10.1155/2016/7342379
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发表时间:
2016
影响因子:
4.3
通讯作者:
Kasper C
Kasper C
中科院分区:
医学3区
文献类型:
--
作者:
Burk J;Plenge A;Brehm W;Heller S;Pfeiffer B;Kasper C

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肌腱和韧带病理仍然是一个治疗的挑战,因为很难恢复复杂的细胞外基质结构和生物力学强度。尽管在基于细胞的治疗和组织工程方法方面取得了进展,但对于祖细胞在肌腱愈合中的命运仍缺乏全面的了解。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自然刺激的影响,这些刺激可能潜在地指导肌腱形成的命运。将马脂肪间充质干细胞种植于脱细胞肌腱基质支架上。在自制的循环应变生物反应器中应用了机械刺激。分别于机械刺激后4 h、8 h和24 h进行评估。支架培养诱导细胞排列和肌腱相关基因表达的变化,尽管细胞活力与单层培养相比有所下降。较短的机械刺激时间增强了支架的大部分诱导效应。胶原1A2的表达水平降低,3A1和核心蛋白的表达水平升高。Tenascin-C和硬化轴的表达开始下降,但在刺激后24 h升高。结果表明,在周期性拉伸的支持下,脱细胞肌腱基质可以诱导肌腱分化和合成对基质重塑至关重要的肌腱成分。
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.
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