Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Cardiovascular Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.
Cell Transplant. 2023 Jan-Dec;32:9636897231156215. doi: 10.1177/09636897231156215.
Healing of full-thickness skin wounds remains a major challenge. Recently, human umbilical cord mesenchymal stem cells (hUC-MSCs) were shown to possess an extraordinary potential to promote skin repair in clinical settings. However, their low survival rate after transplantation limits their therapeutic efficiency in treating full-thickness skin wounds. Hydrogels are considered an ideal cell transplantation vector owing to their three-dimensional mesh structure, good biosafety, and biodegradation. The objective of this study was to investigate the skin wound healing effect of a fibrin hydrogel scaffold loaded with hUC-MSCs. We found that the fibrin hydrogel had a three-dimensional mesh structure and low cytotoxicity and could prolong the time of cell survival in the peri-wound area. The number of green fluorescent protein (GFP)-labeled hUC-MSCs was higher in the full-thickness skin wound of mice treated with hydrogel-hUC-MSCs than those of mice treated with cell monotherapy. In addition, the combination therapy between the hydrogel and hUC-MSCs speed up wound closure, its wound healing rate was significantly higher than those of phosphate-buffered saline (PBS) therapy, hydrogel monotherapy, and hUC-MSCs monotherapy. Furthermore, the results showed that the combination therapy between hydrogel and hUC-MSCs increased keratin 10 and keratin 14 immunofluorescence staining, and upregulated the relative gene expressions of epidermal growth factor (EGF), transforming growth factor-β1 (TGF-β1), and vascular endothelial growth factor A (VEGFA), promoting epithelial regeneration and angiogenesis. In conclusion, the fibrin hydrogel scaffold provides a relatively stable sterile environment for cell adhesion, proliferation, and migration, and prolongs cell survival at the wound site. The hydrogel-hUC-MSCs combination therapy promotes wound closure, re-epithelialization, and neovascularization. It exhibits a remarkable therapeutic effect, being more effective than the monotherapy with hUC-MSCs or hydrogel.
全层皮肤伤口的愈合仍然是一个主要的挑战。最近，人类脐带间充质干细胞（hUC-MSCs）被证明在临床环境中具有非凡的促进皮肤修复的潜力。然而，它们在移植后的低存活率限制了它们在治疗全层皮肤伤口方面的治疗效率。水凝胶因其三维网状结构、良好的生物安全性和可生物降解性而被认为是一种理想的细胞移植载体。本研究旨在探讨负载 hUC-MSCs 的纤维蛋白水凝胶支架对皮肤伤口愈合的影响。我们发现纤维蛋白水凝胶具有三维网状结构和低细胞毒性，可以延长细胞在伤口周围区域的存活时间。在接受水凝胶-hUC-MSCs 治疗的小鼠全层皮肤伤口中，绿色荧光蛋白（GFP）标记的 hUC-MSCs 数量高于接受细胞单药治疗的小鼠。此外，水凝胶与 hUC-MSCs 的联合治疗加速了伤口闭合，其愈合率明显高于磷酸盐缓冲液（PBS）治疗、水凝胶单药治疗和 hUC-MSCs 单药治疗。此外，结果表明，水凝胶与 hUC-MSCs 的联合治疗增加了角蛋白 10 和角蛋白 14 的免疫荧光染色，并上调了表皮生长因子（EGF）、转化生长因子-β1（TGF-β1）和血管内皮生长因子 A（VEGFA）的相对基因表达，促进了上皮再生和血管生成。总之，纤维蛋白水凝胶支架为细胞黏附、增殖和迁移提供了相对稳定的无菌环境，并延长了细胞在伤口部位的存活时间。水凝胶-hUC-MSCs 联合治疗促进了伤口闭合、再上皮化和新生血管形成。它表现出显著的治疗效果，比 hUC-MSCs 或水凝胶单药治疗更有效。
