Curcumin preconditioning enhances the efficacy of adipose-derived mesenchymal stem cells to accelerate healing of burn wounds

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Equine Muscle Derived Mesenchymal Stem Cells Loaded with Water-Soluble Curcumin: Modulation of Neutrophil Activation and Enhanced Protection against Intracellular Oxidative Attack

“…Many studies concern the use of polyphenol in copresence with stem cells for targeting therapeutic application [ 13 ]. Curcumin formulations constitute suitable candidates [ 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. Indeed, curcumin therapy increasingly seems an attractive alternative in patients with contraindication to non-steroidal anti-inflammatory drugs (NSAIDs) [ 43 ].…”

Curcumin-incorporated 3D bioprinting gelatin methacryloyl hydrogel reduces reactive oxygen species-induced adipose-derived stem cell apoptosis and improves implanting survival in diabetic wounds

“…In addition, liposomal Cur has been demonstrated to enhance the activity of endothelial-differentiated-human periodontal ligament stem cells and dental pulp stem cells as an anti-inflammatory strategy [ 44 , 45 ]. In addition, Cur pretreated ADSCs can accelerate the re-epithelialization and angiogenesis of acid inflicted burn wounds [ 46 ]. Here, we demonstrated that Cur reduced AGE-induced AGER and caspase-3 expression, ROS production, apoptosis and NF-κB p65 activation.…”

Mesenchymal Stem Cells in Burn Wound Management

“…Curcumin-preconditioned ADSCs had an increased capacity for migration, proliferation, and paracrine potential, suppressed secretion of pro-inflammatory cytokines, and improved healing in comparison with innate ADSCs [ 52 ]. In a rat burn model, autologous ADSCs were seeded in a PRP matrix and injected under the meshed skin graft to improve healing and neovascularization [ 70 ].…”