Journal Article

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

He, Jinyang, Chu, Jing, Deng, Xiaoyuan, Liu, Hanping, He, Chengmin, Yang, Zhi

2018

Overview

Background Adult 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. Methods In 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). Results In 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 T H 1 cells (interferon gamma) and M1 macrophages (tumor necrosis factor alpha) genes were confirmed at 7 days post-operation. The number of T H 1 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. Conclusions Curcumin has a good regulatory effect on BMSCs and this promising CS-C biomaterial creates a pro-regenerative immune microenvironment for cutaneous wound healing.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Allografts / Analysis / Animals / Biomedical and Life Sciences / Biomedical Engineering and Bioengineering / Bone marrow cells / Bone Marrow Cells - immunology / Bone Marrow Cells - pathology / Bone marrow mesenchymal stem cell / Cell Biology / Cell sheet / Cellular Microenvironment - drug effects / Cellular Microenvironment - immunology / Curcumin / Curcumin - pharmacology / Cutaneous wound healing / Health aspects / Immune response / Life Sciences / Macrophages - immunology / Macrophages - pathology / Male / Mesenchymal Stem Cell Transplantation / Mesenchymal Stem Cells - immunology / Mesenchymal Stem Cells - pathology / Mice / Mice, Inbred BALB C / Mice, Transgenic / Physiological aspects / Regenerative Medicine/Tissue Engineering / Stem Cells / Th1 Cells - immunology / Th1 Cells - pathology / Wound healing / Wound Healing - immunology / Wounds and Injuries - immunology / Wounds and Injuries - pathology / Wounds and Injuries - therapy