Capillary Force Seeding of Hydrogels for Adipose-Derived Stem Cell Delivery in Wounds
Capillary Force Seeding of Hydrogels for Adipose-Derived Stem Cell Delivery in Wounds
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DOI：
10.5966/sctm.2014-0007
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发表时间：
2014-09-01
影响因子：
6
通讯作者：
Gurtner, Geoffrey C.
中科院分区：
文献类型：
--
作者：
Garg, Ravi K.;Rennert, Robert C.;Gurtner, Geoffrey C.
有效的皮肤再生疗法需要祖细胞和生物相容递送系统之间的成功接口。我们之前展示了一种仿生普鲁兰-胶原水凝胶支架，通过创造一个促进再生细胞因子分泌的“干细胞生态位”，提高了骨髓间充质干细胞在缺血性皮肤伤口中的存活能力。脂肪来源的间充质干细胞(ASCs)因其丰富性和可获得性而成为更具吸引力的干细胞来源，在本研究中，我们探索了ASCs在水凝胶治疗中的应用。为了优化水凝胶细胞的接种，开发了一种基于毛细管力的快速方法，并与以前建立的细胞接种方法进行了比较。然后在体外和体内分析毛细血管水凝胶种植后ASC的活性和功能。在这些实验中，通过毛细管力比传统方法更有效地种植ASCs，并在这个利基环境中保持存活和功能长达14天。此外，ASCs水凝胶接种后多种血管生成相关基因表达增强，包括Oct4、VEGF、MCP-1和SDF-1。体内移动，水凝胶输送提高了ASC存活率，与未接种水凝胶治疗的对照伤口相比，将小鼠和人ASC种子水凝胶应用于夹板小鼠伤口可加速伤口闭合并增加血管。总之，在普鲁兰-胶原水凝胶生物支架内种植ASCs提供了一种将治疗细胞输送到伤口环境的方便和简单的方法。此外，ASC种子构建物在加速伤口愈合方面显示出巨大的潜力，这很容易转化为临床环境。
Effective skin regeneration therapies require a successful interface between progenitor cells and biocompatible delivery systems. We previously demonstrated the efficiency of a biomimetic pullulan-collagen hydrogel scaffold for improving bone marrow-derived mesenchymal stem cell survival within ischemic skin wounds by creating a "stem cell niche" that enhances regenerative cytokine secretion. Adipose-derived mesenchymal stem cells (ASCs) represent an even more appealing source of stem cells because of their abundance and accessibility, and in this study we explored the utility of ASCs for hydrogel-based therapies. To optimize hydrogel cell seeding, a rapid, capillary force-based approach was developed and compared with previously established cell seeding methods. ASC viability and functionality following capillary hydrogel seeding were then analyzed in vitro and in vivo. In these experiments, ASCs were seeded more efficiently by capillary force than by traditional methods and remained viable and functional in this niche for up to 14 days. Additionally, hydrogel seeding of ASCs resulted in the enhanced expression of multiple sternness and angiogenesis-related genes, including Oct4, Vegf, Mcp-1, and Sdf-1. Moving in vivo, hydrogel delivery improved ASC survival, and application of both murine and human ASC-seeded hydrogels to splinted murine wounds resulted in accelerated wound closure and increased vascularity when compared with control wounds treated with unseeded hydrogels. In conclusion, capillary seeding of ASCs within a pullulan-collagen hydrogel bioscaffold provides a convenient and simple way to deliver therapeutic cells to wound environments. Moreover, ASC-seeded constructs display a significant potential to accelerate wound healing that can be easily translated to a clinical setting.