Dimeric Thymosin β4 Loaded Nanofibrous Interface Enhanced Regeneration of Muscular Artery in Aging Body through Modulating Perivascular Adipose Stem Cell-Macrophage Interaction.,Advanced Science

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Dimeric Thymosin β4 Loaded Nanofibrous Interface Enhanced Regeneration of Muscular Artery in Aging Body through Modulating Perivascular Adipose Stem Cell-Macrophage Interaction.
Advanced Science ( IF 14.3 ) Pub Date : 2020-03-16 , DOI: 10.1002/advs.201903307
Wanli Chen ₁ , Sansan Jia ₁ , Xinchi Zhang ₁ , Siqian Zhang ₁ , Huan Liu ₂ , Xin Yang ₁ , Cun Zhang ₃ , Wei Wu ₁

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Regenerating nonthrombotic and compliant artery, especially in the aging body, remains a major surgical challenge, mainly owing to the inadequate knowledge of the major cell sources contributing to arterial regeneration and insufficient bioactivity of delivered peptides in grafts. Ultrathin nanofibrous sheaths stented with biodegrading elastomer present opening channels and reduced material residue, enabling fast cell recruitment and host remodeling, while incorporating peptides offering developmental cues are challenging. In this study, a recombinant human thymosin β4 dimer (DTβ4) that contains two complete Tβ4 molecules is produced. The adult perivascular adipose is found as the dominant source of vascular progenitors which, when stimulated by the DTβ4-loaded nanofibrous sheath, enables 100% patency rates, near-complete structural as well as adequate functional regeneration of artery, and effectively ameliorates aging-induced defective regeneration. As compared with Tβ4, DTβ4 exhibits durable regenerative activity including recruiting more progenitors for endothelial cells and smooth muscle cells, when incorporated into the ultrathin polycaprolactone sheath. Moreover, the DTβ4-loaded interface promotes smooth muscle cells differentiation, mainly through promoting M2 macrophage polarization and chemokines. Incorporating artificial DTβ4 into ultrathin sheaths of fast degrading vascular grafts creates an effective interface for sufficient muscular remodeling thus offering a robust tool for vessel replacement.

中文翻译：

二聚胸腺素 β4 负载纳米纤维界面通过调节血管周围脂肪干细胞-巨噬细胞相互作用增强衰老身体中肌肉动脉的再生。

再生非血栓性和顺应性动脉，特别是在衰老的身体中，仍然是一项重大的外科挑战，这主要是由于对有助于动脉再生的主要细胞来源了解不足以及移植物中递送的肽的生物活性不足。采用生物降解弹性体支架的超薄纳米纤维鞘呈现开放通道并减少材料残留，从而实现快速细胞募集和宿主重塑，同时掺入提供发育线索的肽具有挑战性。在本研究中，产生了包含两个完整的Tβ4分子的重组人胸腺素β4二聚体（DTβ4）。成人血管周围脂肪被发现是血管祖细胞的主要来源，当受到载有 DTβ4 的纳米纤维鞘的刺激时，可以实现 100% 的通畅率、近乎完整的动脉结构和充分的功能再生，并有效改善衰老引起的动脉粥样硬化。再生缺陷。与 Tβ4 相比，DTβ4 当纳入超薄聚己内酯鞘时，表现出持久的再生活性，包括招募更多的内皮细胞和平滑肌细胞祖细胞。此外，负载DTβ4的界面主要通过促进M2巨噬细胞极化和趋化因子来促进平滑肌细胞分化。将人工 DTβ4 纳入快速降解血管移植物的超薄鞘中，为充分的肌肉重塑创造了有效的界面，从而为血管置换提供了强大的工具。

更新日期：2020-04-21

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