PF-127 hydrogel plus sodium ascorbyl phosphate improves Wharton's jelly mesenchymal stem cell-mediated skin wound healing in mice
PF-127 hydrogel plus sodium ascorbyl phosphate improves Wharton's jelly mesenchymal stem cell-mediated skin wound healing in mice
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PF-127水凝胶加抗坏血酸磷酸钠可改善沃顿胶间充质干细胞介导的小鼠皮肤伤口愈合
DOI：
10.1186/s13287-020-01638-2
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发表时间：
2020-04-03
影响因子：
7.5
通讯作者：
Huang, Junjiu
中科院分区：
文献类型：
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作者：
Deng, Qingzha;Huang, Sunxing;Huang, Junjiu
背景因素如移植干细胞的植入、保留和存活不良被认为限制了它们对伤口再生的治疗效果。因此，有必要探讨这些问题，以解决它们。在这项研究中，我们的目的是研究Pluronic F-127（PF-127）水凝胶加抗氧化剂抗坏血酸磷酸钠（SAP）在增强沃顿胶质间充质干细胞（WJMSC）介导的小鼠全层皮肤伤口愈合有效性方面的作用。方法采用细胞活力和增殖实验检测PF-127的细胞毒性和SAP对WJMSCs的生物学效应。接下来，将含有WJMSC、PF-127和SAP的细胞悬浮液局部施用到8 mm直径的切除全层伤口床上。移植后8天，处死小鼠，切除皮肤组织进行组织学和免疫组织化学分析。最后，追踪移植的WJMSCs在体内的分布，以研究细胞植入和潜在的治疗机制。结果PF-127对WJMSCs具有细胞毒性，SAP可显著提高PF-127包埋的WJMSCs的存活率。当将该组合局部移植到伤口床上时，促进了伤口愈合，并且在手术后第8天实现了真皮再生，如真皮厚度增加、新发育的毛囊和胶原纤维沉积伴随着疤痕宽度减小所证明的。此外，免疫组织化学分析表明，相对于所有其他组，WJMSC/PF-127/SAP组中的抗炎M2巨噬细胞、增殖细胞和新形成的血管的数量更高。此外，体内追踪结果显示，在WJMSCs/PF-127/SAP组中，在真皮中积累的WJMSCs的植入高度增强。结论SAP可显著提高PF-127包埋的WJMSCs的存活率。此外，PF-127加SAP是一种有效的组合，可增强WJMSC在真皮中的植入，然后通过潜在的M2巨噬细胞形成和血管生成促进全层伤口愈合。
Background Factors such as poor engraftment, retention, and survival of the transplanted stem cells are deemed to limit their therapeutic efficacy for wound regeneration. Hence, it is necessary to explore these issues in order to resolve them. In this study, we aim to investigate the role of Pluronic F-127 (PF-127) hydrogel plus antioxidant sodium ascorbyl phosphate (SAP) in enhancing Wharton's jelly mesenchymal stem cell (WJMSC)-mediated effectiveness on full-thickness skin wound healing in mice. Methods First, the cytotoxicity of PF-127 and the biological effect of SAP on the survival of WJMSCs were tested in vitro using cell viability and proliferation assays. Next, a cell suspension containing WJMSCs, PF-127, and SAP was topically administered onto an 8-mm diameter excisional full-thickness wound bed. Eight days after transplantation, the mice were sacrificed and the skin tissue was excised for histological and immunohistochemical analysis. Finally, in vivo distribution of transplanted WJMSCs was traced to investigate cell engraftment and the potential therapeutic mechanism. Results PF-127 was found to be cytotoxic to WJMSCs while SAP significantly improved the survival of PF-127-embedded WJMSCs. When this combination was topically transplanted onto the wound bed, wound healing was facilitated and dermis regeneration was achieved on the 8th day after surgery, as evidenced by an increase in dermal thickness, newly developed hair follicles, and collagen fiber deposition accompanied by a reduction in scar width. Further, immunohistochemical analysis demonstrated a higher number of anti-inflammatory M2 macrophages, proliferating cells, and newly formed blood vessels in the WJMSCs/PF-127/SAP group relative to all other groups. In addition, in vivo tracking results revealed a highly enhanced engraftment of WJMSCs accumulated in the dermis in the WJMSCs/PF-127/SAP group. Conclusions SAP significantly improves the survival of WJMSCs in PF-127 encapsulation. Further, PF-127 plus SAP is an effective combination that enhances WJMSC engraftment in the dermis, which then promotes full-thickness wound healing through potential M2 macrophage formation and angiogenesis.