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.
Highlights
Adult full-thickness cutaneous wound repair suffers from an imbalanced immune response, leading to nonfunctional reconstructed tissue and fibrosis
We focused on investigating the functional role of curcumin, its ability to regulate bone marrow-derived mesenchymal stem cell (BMSC) behavior and extracellular matrix (ECM) production, and to create a favorable immune microenvironment for adult full-thickness cutaneous wound healing
The macroscopic shape of this sheet (5×). c hematoxylin and eosin (H&E) staining of BMSC sheets which contained many layers of cells. d Scanning electron microscope image of the BMSC sheet; the arrows point to mesenchymal stem cells (MSCs) (1 kx, 20 μm). e Fluorescence microscope image of the BMSC sheet; green and blue show the cytoskeleton of green fluorescent protein (GFP)+ BMSCs and cell nuclei, respectively (63×, 5 μm). f Second harmonic imaging (SHG) image of the BMSC sheet; red and green represent collagen and cells, respectively (40×, 20 μm) cell sheet was observed using a stereomicroscope (Fig. 1b) and exhibited a certain thickness and flexibility
Summary
Adult full-thickness cutaneous wound repair suffers from an imbalanced immune response, leading to nonfunctional reconstructed tissue and fibrosis. Adult full-thickness cutaneous wounds, caused by burning, mechanical injury, or chronic ulcers, and so forth, usually lead to a non-functional tissue known as a scar [1, 2]. Tissuerepairing M2 macrophages possess anti-inflammatory properties and support the functions of T helper 2 (TH2)associated effector cells [7]. These two types of cells work together to promote tissue repair by expressing several wound healing factors such as arginase, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF)α, and insulin-like growth factor (IGF) [8,9,10]
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