School of Life Sciences, Zhengzhou University, No. 100 Science Avenue, Zhengzhou, 450001, Henan, China.
Stem Cell Research Center, Henan Provincial People's Hospital, Zhengzhou, 450003, Henan, China.
Cell Tissue Res. 2021 Feb;383(2):809-821. doi: 10.1007/s00441-020-03321-7. Epub 2020 Nov 7.
Stem cell transplantation is a promising therapy for wound healing, but the low retention and survival of transplanted stem cells limit their application. Injectable hydrogels exert beneficial effects in skin tissue engineering. In this study, an injectable hydrogel composed of sodium alginate (SA) and collagen type I (Col) was synthesized as a tissue scaffold to improve the efficacy of stem cells in a full-thickness excision wound model. Our results showed that SA/Col hydrogel was injectable, biodegradable, and exhibited low immunogenicity, which could promote the retention and survival of hUC-MSCs in vivo. SA/Col loaded with hUC-MSCs showed reduced wound size (p < 0.05). Histological and immunofluorescence results confirmed that SA/Col loaded with hUC-MSCs significantly promoted the formation of granulation, enhanced collagen deposition and angiogenesis, increased VEGF and TGF-β1 expression (p < 0.05), and mitigated inflammation evidenced by lower production of TNF-α and IL-1β and higher release of IL-4 and IL-10 (p < 0.05). Furthermore, SA/Col loaded with hUC-MSCs significantly lowered the expression of NLRP3 inflammasome-related proteins (p < 0.05). Taken together, our results suggest that SA/Col loaded with hUC-MSCs promotes skin wound healing via partly inhibiting NLRP3 pathway, which has potential to the treatment of skin wounds.
干细胞移植是一种有前途的伤口愈合治疗方法,但移植干细胞的低保留率和存活率限制了其应用。可注射水凝胶在皮肤组织工程中具有有益作用。在这项研究中,合成了一种由海藻酸钠(SA)和 I 型胶原(Col)组成的可注射水凝胶作为组织支架,以提高全层切除伤口模型中干细胞的疗效。我们的结果表明,SA/Col 水凝胶具有可注射性、可生物降解性和低免疫原性,可促进 hUC-MSCs 在体内的保留和存活。负载 hUC-MSCs 的 SA/Col 显示出减小的伤口面积(p<0.05)。组织学和免疫荧光结果证实,负载 hUC-MSCs 的 SA/Col 显著促进了肉芽组织的形成,增强了胶原沉积和血管生成,增加了 VEGF 和 TGF-β1 的表达(p<0.05),并通过降低 TNF-α 和 IL-1β 的产生和提高 IL-4 和 IL-10 的释放来减轻炎症(p<0.05)。此外,负载 hUC-MSCs 的 SA/Col 显著降低了 NLRP3 炎性小体相关蛋白的表达(p<0.05)。总之,我们的结果表明,负载 hUC-MSCs 的 SA/Col 通过部分抑制 NLRP3 途径促进皮肤伤口愈合,这为皮肤伤口的治疗提供了潜力。