Curcumin-mediated bone marrow mesenchymal stem cell sheets create a favorable immune microenvironment for adult full-thickness cutaneous wound healing

Abstract

BackgroundAdult full-thickness cutaneous wound repair suffers from an imbalanced immune response, leading to nonfunctional reconstructed tissue and fibrosis. Although various treatments have been reported, the immune-mediated tissue regeneration driven by biomaterial offers an attractive regenerative strategy for damaged tissue repair.MethodsIn this research, we investigated a specific bone marrow-derived mesenchymal stem cell (BMSC) sheet that was induced by the Traditional Chinese Medicine curcumin (CS-C) and its immunomodulatory effects on wound repair. Comparisons were made with the BMSC sheet induced without curcumin (CS-N) and control (saline).ResultsIn vitro cultured BMSC sheets (CS-C) showed that curcumin promoted the proliferation of BMSCs and modified the features of produced extracellular matrix (ECM) secreted by BMSCs, especially the contents of ECM structural proteins such as fibronectin (FN) and collagen I and III, as well as the ratio of collagen III/I. Two-photon fluorescence (TPF) and second-harmonic generation (SHG) imaging of mouse implantation revealed superior engraftment of BMSCs, maintained for 35 days in the CS-C group. Most importantly, CS-C created a favorable immune microenvironment. The chemokine stromal cell-derived factor 1 (SDF1) was abundantly produced by CS-C, thus facilitating a mass migration of leukocytes from which significantly increased expression of signature TH1 cells (interferon gamma) and M1 macrophages (tumor necrosis factor alpha) genes were confirmed at 7 days post-operation. The number of TH1 cells and associated pro-inflammatory M1 macrophages subsequently decreased sharply after 14 days post-operation, suggesting a rapid type I immune regression. Furthermore, the CS-C group showed an increased trend towards M2 macrophage polarization in the early phase. CS-C led to an epidermal thickness and collagen deposition that was closer to that of normal skin.ConclusionsCurcumin has a good regulatory effect on BMSCs and this promising CS-C biomaterial creates a pro-regenerative immune microenvironment for cutaneous wound healing.

Wound healing improvement by curcumin‐loaded electrospun nanofibers and BFP‐MSCs as a bioactive dressing

“…However, there was a thicker granulation tissue and better‐aligned collagen fibers in the scaffold/Cur group in comparison with the scaffold/Cur/BFP‐MSCs group. Recently, Yang et al reported that Cur has a positive regulatory effect on BM‐MSCs and thus provides a pro‐RG immune microenvironment for cutaneous wound healing . Another study introduced pretreatment with Cur as a promising adjuvant strategy for the transplantation of stem cells in myocardial restoration, but our result did not show an antagonist effect of Cur and stem cells in enhancing the wound‐healing rate.…”

Microskin‐Inspired Injectable MSC‐Laden Hydrogels for Scarless Wound Healing with Hair Follicles

“…Both the introduction of SFN hydrogels and BMSCs facilitated more vessel formation since the SF nanofibers could induce the migration of endothelial cells while BMSCs could recruit the cells through paracrine effects (Figure 7a b’–d’, b’’–d’’). [ 7,16b ] Further improvement of angiogenesis was achieved in the wounds treated with the BMSC‐laden SFN hydrogels due to the cooperative effect of SFN hydrogels and BMCs (Figure 7a e’, e’’). Finally, the LP particles with aligned structures actively regulated the secretion behavior of the BMCs, resulting in the most extensive vascularization in the wounds treated with the BMSC‐laden SFN‐LP hydrogels (Figure 7a f’, f’’).…”

“…Unlike previous injectable BMSCs‐laden systems, [ 7,30 ] these new hydrogels were composed of two flexible SFN units, endowing the hydrogel system with tunability. The content of LP particles and the amount of BMSCs can be regulated to optimize the niche for wound healing.…”

“…[ 6 ] By sensing the microenvironment of these cell‐laden biomaterial systems, SCs can regulate immune responses, vascularization, cell recruitment, and tissue remodeling. [ 5a,b,7 ] However, a gap exists for SCs strategies to achieve scarless skin tissue outcomes, thus improved SCs‐laden biomaterial systems are required to strengthen the action of SCs in skin regeneration.…”

Stem Cell Therapy: Curcumin Does the Trick

“…Besides, the curcumin showed improved effect on the efficacy and delivery of BMSCs to reinforce its prohealing functions. Based on their conclusion, curcumin‐induced BMSC sheet presented impressive results for adult full‐thickness cutaneous wound healing, which will be a new viewpoint for the future treatment for repair of skin wound (Yang et al, ).…”