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首页> 外文期刊>Acta biomaterialia >The effect of decellularized matrices on human tendon stem/progenitor cell differentiation and tendon repair
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The effect of decellularized matrices on human tendon stem/progenitor cell differentiation and tendon repair

机译：去细胞基质对人肌腱干/祖细胞分化和肌腱修复的影响

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It is reported that decellularized collagen matrices derived from dermal skin and bone have been clinically used for tendon repair. However, the varying biological and physical properties of matrices originating from different tissues may influence the differentiation of tendon stem cells, which has not been systematically evaluated. In this study, the effects of collagenous matrices derived from different tissues (tendon, bone and dermis) on the cell differentiation of human tendon stem/progenitor cells (hTSPCs) were investigated, in the context of tendon repair. It was found that all three matrices supported the adhesion and proliferation of hTSPCs despite differences in topography. Interestingly, tendon-derived decellularized matrix promoted the tendinous phenotype in hTSPCs and inhibited their osteogenesis, even under osteogenic induction conditions, through modulation of the teno- and osteolineage-specific transcription factors Scleraxis and Runx2. Bone-derived decellularized matrix robustly induced osteogenic differentiation of hTSPCs, whereas dermal skin-derived collagen matrix had no apparent effect on hTSPC differentiation. Based on the specific biological function of the tendon-derived decellularized matrix, a tissue-engineered tendon comprising TSPCs and tendon-derived matrix was successfully fabricated for Achilles tendon reconstruction. Implantation of this cell-scaffold construct led to a more mature structure (histology score: 4.08 ± 0.61 vs. 8.51 ± 1.66), larger collagen fibrils (52.2 ± 1.6 nm vs. 47.5 ± 2.8 nm) and stronger mechanical properties (stiffness: 21.68 ± 7.1 Nm m-1 vs.13.2 ± 5.9 Nm m-1) of repaired tendons compared to the control group. The results suggest that stem cells promote the rate of repair of Achilles tendon in the presence of a tendinous matrix. This study thus highlights the potential of decellularized matrix for future tissue engineering applications, as well as developing a practical strategy for functional tendon regeneration by utilizing TSPCs combined with tendon-derived decellularized matrix.
机译：据报道，源自真皮和骨骼的脱细胞胶原蛋白基质已在临床上用于肌腱修复。然而，源自不同组织的基质的不同生物学和物理性质可能会影响肌腱干细胞的分化，这尚未得到系统评价。在这项研究中，在肌腱修复的背景下，研究了源自不同组织（肌腱，骨骼和真皮）的胶原蛋白基质对人肌腱干/祖细胞（hTSPCs）细胞分化的影响。已发现尽管形貌不同，所有三种基质均支持hTSPC的粘附和增殖。有趣的是，即使在成骨诱导条件下，肌腱衍生的脱细胞基质也可通过调节Teno和骨谱系特异性转录因子Scleraxis和Runx2促进hTSPCs的肌腱表型并抑制其成骨作用。骨来源的脱细胞基质强烈诱导hTSPCs的成骨分化，而真皮来源的胶原蛋白基质对hTSPC的分化没有明显影响。基于腱衍生的脱细胞基质的特定生物学功能，成功制备了包含TSPC和腱衍生基质的组织工程腱，用于跟腱重建。植入该细胞支架构建体导致更成熟的结构（组织学评分：4.08±0.61对8.51±1.66），更大的胶原纤维（52.2±1.6 nm对47.5±2.8 nm）和更强的机械性能（刚度：21.68）与对照组相比，修复后的肌腱为±7.1 Nm m-1 vs.13.2±5.9 Nm m-1）。结果表明，在存在肌腱基质的情况下，干细胞可促进跟腱的修复速率。因此，这项研究强调了脱细胞基质在未来组织工程应用中的潜力，以及通过结合TSPC与腱衍生的脱细胞基质一起开发功能性腱再生的实用策略。

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