Establishing in vivo and ex vivo chick embryo models to investigate fetal tendon healing.

Establishing in vivo and ex vivo chick embryo models to investigate fetal tendon healing.
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DOI:
10.1038/s41598-023-35408-w
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发表时间:
2023-06-13
期刊:
影响因子:
4.6
通讯作者:
--
中科院分区:
综合性期刊3区
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--
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受伤的成人肌腱纤维化愈合,并具有较高的再损伤率,而胎儿肌腱似乎愈合疤痕。然而,胎儿肌腱伤口愈合的知识是有限的,部分原因是需要一个可访问的动物模型。在这里,我们开发了体内和体外鸡胚肌腱模型,研究胎儿肌腱愈合的特点。在这两种模型中,损伤部位在愈合过程中迅速充满细胞和细胞外基质,体内伤口闭合更快。在早期胚胎阶段受伤的肌腱改善机械性能的水平类似于未受伤的控制,而肌腱在胚胎后期受伤没有。肌腱表型标志物、胶原、胶原交联调节剂、基质金属蛋白酶和促炎介质的表达水平在愈合过程中表现出胚胎阶段依赖性趋势。细胞凋亡发生在愈合过程中,但离体肌腱表现出更高水平的细胞凋亡比肌腱在体内。未来的研究将使用这些体内和离体鸡胚肌腱损伤模型来阐明阶段特异性胎儿肌腱愈合的机制,以告知再生愈合成人肌腱的治疗方法的发展。
Injured adult tendons heal fibrotically and possess high re-injury rates, whereas fetal tendons appear to heal scarlessly. However, knowledge of fetal tendon wound healing is limited due in part to the need for an accessible animal model. Here, we developed and characterized an in vivo and ex vivo chick embryo tendon model to study fetal tendon healing. In both models, injury sites filled rapidly with cells and extracellular matrix during healing, with wound closure occurring faster in vivo. Tendons injured at an earlier embryonic stage improved mechanical properties to levels similar to non-injured controls, whereas tendons injured at a later embryonic stage did not. Expression levels of tendon phenotype markers, collagens, collagen crosslinking regulators, matrix metalloproteinases, and pro-inflammatory mediators exhibited embryonic stage-dependent trends during healing. Apoptosis occurred during healing, but ex vivo tendons exhibited higher levels of apoptosis than tendons in vivo. Future studies will use these in vivo and ex vivo chick embryo tendon injury models to elucidate mechanisms of stage-specific fetal tendon healing to inform the development of therapeutic approaches to regeneratively heal adult tendons.
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