Curcumin preconditioning enhances the efficacy of adipose-derived mesenchymal stem cells to accelerate healing of burn wounds.
Curcumin preconditioning enhances the efficacy of adipose-derived mesenchymal stem cells to accelerate healing of burn wounds.
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DOI：
10.1093/burnst/tkab021
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发表时间：
2021
期刊：
影响因子：
5.3
通讯作者：
Riazuddin S
中科院分区：
文献类型：
--
作者：
Azam M;Ghufran H;Butt H;Mehmood A;Ashfaq R;Ilyas AM;Ahmad MR;Riazuddin S
根据我们小组最近的研究结果，姜黄素预处理增强了脂肪源性干细胞在大鼠糖尿病伤口愈合中的治疗效果，本研究旨在研究姜黄素预处理脂肪源性间充质干细胞（ASCs）对酸烧伤愈合的再生作用。用5 μM姜黄素预处理ASCs 24小时，比较naïve ASCs的增殖、迁移、旁分泌释放潜能和基因表达。随后，姜黄素预处理ASCs （curc -ASCs）与naïve ASCs的愈合能力在大鼠酸性伤口中进行了比较。为此，在雄性Wistar大鼠背部做了直径20毫米的酸烧伤。然后，将2 × 106个curc -ASCs和naïve ASCs细胞皮内注射于创面周围（n = 6），与未处理的生理盐水对照组进行比较。移植后，对创面进行宏观分析和拍照，以评估创面愈合的百分比和再上皮化的时间。切除愈合创面活检组织，采用定量PCR和western blotting方法在分子水平上对创面愈合标志物进行组织学评价和表达分析。我们发现curc - ascs在体外表现出更大的增殖、迁移和旁分泌潜能。此外，curc -ASCs表现出比naïve ASCs更有效的恢复，表现在大体形态、更快的伤口愈合和更早的再上皮化。马松三色、苏木精和伊红染色显示愈合烧伤的结构得到改善，这可以通过减少炎症细胞的浸润、致密的胶原蛋白和显著的肉芽形成来证明。与这些发现相一致的是，分子评估显示促炎因子（白细胞介素-1 β、白细胞介素-6、肿瘤坏死因子α） a的表达显著降低，氧化标志物（超氧化物歧化酶1）、促血管生成因子（血管内皮生长因子、肝细胞生长因子、缺氧诱导因子-1 α）和胶原标志物（转化生长因子β 1、成纤维细胞生长因子-2、1型胶原α 1）的表达显著增加。验证curc - ascs调节烧伤部位的促炎和愈合标记物的调节。与naïve ASCs治疗相比，cu -ASCs治疗导致酸烧伤的再上皮形成更快。基于观察结果，我们认为curc - ascs移植是一种有效的临床治疗酸性烧伤的有价值的治疗方法。
Following recent findings from our group that curcumin preconditioning augments the therapeutic efficacy of adipose-derived stem cells in the healing of diabetic wounds in rats, we aimed to investigate the regenerative effects of curcumin preconditioned adipose-derived mesenchymal stem cells (ASCs) for better recovery of acid inflicted burns in this study. ASCs were preconditioned with 5 μM curcumin for 24 hours and assessed for proliferation, migration, paracrine release potential and gene expression comparative to naïve ASCs. Subsequently, the healing capacity of curcumin preconditioned ASCs (Cur-ASCs) versus naïve ASCs was examined using acidic wounds in rats. For this, acid inflicted burns of 20 mm in diameter were made on the back of male Wistar rats. Then, 2 × 106 cells of Cur-ASCs and naïve ASCs were intradermally injected in the wound periphery (n = 6) for comparison with an untreated saline control. Post-transplantation, wounds were macroscopically analysed and photographed to evaluate the percentage of wound closure and period of re-epithelization. Healed wound biopsies were excised and used for histological evaluation and expression analysis of wound healing markers at molecular level by quantitative PCR and western blotting. We found that Cur-ASCs exhibited greater proliferation, migration and paracrine potential in vitro. Further, Cur-ASCs showed more effective recovery than naïve ASCs as exhibited by gross morphology, faster wound closure and earlier re-epithelialization. Masson’s trichrome and hematoxylin and eosin staining demonstrated the improved architecture of the healing burns, as evidenced by reduced infiltration of inflammatory cells, compact collagen and marked granulation in Cur-ASC treated rats. Corroborating these findings, molecular assessment showed significantly reduced expressions of pro-inflammatory factors (interleukin-1 beta, interleukin-6, tumor necrosis factor alpha) a with striking upsurge of an oxidative marker (superoxide dismutase 1), pro-angiogenic factors (vascular endothelial growth factor, hepatocyte growth factor, hypoxia-inducible factor-1 alpha) and collagen markers (transforming growth factor beta 1, fibroblast growth factor-2, collagen type 1 alpha 1), verifying that Cur-ASCs modulate the regulation of pro-inflammatory and healing markers at burn sites. Treatment with Cur-ASCs resulted in faster re-epithelization of acid inflicted burns compared to the treatment with naïve ASCs. Based on observed findings, we suggest the transplantation of Cur-ASCs is a valuable therapy for the potent clinical management of acidic burns.
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DOI：
10.1016/j.jtos.2015.11.004
发表时间：
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期刊：
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