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Mesenchymal stem cells delivered in a microsphere-based engineered skin contribute to cutaneous wound healing and sweat gland repair

机译:在基于微球的工程皮肤中递送的间充质干细胞有助于皮肤伤口愈合和汗腺修复

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Background: Bone-marrow-derived mesenchymal stem cells (BM-MSCs) can contribute to wound healing after skin injury. However, the role of BM-MSCs on repairing skin appendages in renewal tissues is incompletely explored. Moreover, most preclinical studies suggest that the therapeutic effects afforded by BM-MSCs transplantation are short-lived and relatively unstable. Objective: To assess whether engrafted bone-marrow-derived mesenchymal stem cells via a delivery system can participate in cutaneous wound healing and sweat-gland repair in mice. Methods: For safe and effective delivery of BM-MSCs to wounds, epidermal growth factor (EGF) microspheres were firstly developed to both support cells and maintain appropriate stimuli, then cell-seeded microspheres were incorporated with biomimetic scaffolds and thus fabricated an engineered skin construct with epithelial differentiation and proliferative potential. The applied efficacy was examined by implanting them into excisional wounds on both back and paws of hind legs in mice. Results: After 3 weeks, BM-MSC-engineered skin (EGF loaded) treated wounds exhibited accelerated healing with increased re-epithelialization rates and less skin contraction. Furthermore, histological and immunofluorescence staining analysis revealed sweat glands-like structures became more apparent in BM-MSC-engineered skin (EGF loaded) treated wounds but the number of implanted BM-MSCs were decreased gradually in later phases of healing progression. Conclusions: Our study suggests that BM-MSCs delivered by this EGF microspheres-based engineered skin model may be a promising strategy to repair sweat glands and improve cutaneous wound healing after injury and success in this study might provide a potential benefit for BM-MSCs administration clinically.
机译:背景:骨髓间充质干细胞(BM-MSC)可以促进皮肤损伤后的伤口愈合。但是,尚未完全探讨BM-MSC在修复更新组织中皮肤附件中的作用。此外,大多数临床前研究表明,BM-MSCs移植所提供的治疗作用是短暂的且相对不稳定。目的:评估通过递送系统植入的骨髓间充质干细胞是否可以参与小鼠的皮肤伤口愈合和汗腺修复。方法:为了安全,有效地将BM-MSC递送至伤口,首先开发了表皮生长因子(EGF)微球以支持细胞并维持适当的刺激,然后将细胞接种的微球与仿生支架整合在一起,从而制造出了工程化的皮肤构建体具有上皮分化和增殖潜能。通过将它们植入小鼠后腿背部和脚掌的切除伤口中,检查其应用功效。结果:3周后,经BM-MSC工程处理的皮肤(负载EGF)治疗的伤口显示出加速的愈合,增加了上皮形成速率,并且皮肤收缩较少。此外,组织学和免疫荧光染色分析显示,在BM-MSC工程皮肤(负载EGF)处理的伤口中,汗腺样结构变得更加明显,但在愈合进展的后期阶段,植入的BM-MSC的数量逐渐减少。结论:我们的研究表明,这种基于EGF微球的工程皮肤模型提供的BM-MSCs可能是修复汗腺并改善损伤后皮肤伤口愈合的有前途的策略,该研究的成功可能为BM-MSCs的管理提供潜在的益处临床上。

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