IGF-1C hydrogel improves the therapeutic effects of MSCs on colitis in mice through PGE₂-mediated M2 macrophage polarization

Abstract

Background: Mesenchymal stem cell (MSC)-based therapies hold great promise for the treatment of inflammatory bowel disease (IBD). In order to optimize and maximize the therapeutic benefits of MSCs, we investigated whether cotransplantation of a chitosan (CS)-based injectable hydrogel with immobilized IGF-1 C domain peptide (CS-IGF-1C) and human placenta-derived MSCs (hP-MSCs) could ameliorate colitis in mice. Methods: IGF-1C hydrogel was generated by immobilizing IGF-1C to CS hydrogel. Colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice. We initially applied hP-MSCs and CS-IGF-1C hydrogel for the treatment of colitis by in situ injection, and molecular imaging methods were used for real-time imaging of reactive oxygen species (ROS) and tracking of transplanted hP-MSCs by bioluminescence imaging (BLI). Furthermore, the effects of CS-IGF-1C hydrogel on prostaglandin E 2 (PGE 2 ) secretion of hP-MSCs and polarization of M2 macrophages were investigated as well. Results: The CS-IGF-1C hydrogel significantly increased hP-MSC proliferation and promoted the production of PGE 2 from hP-MSCs in vitro . Moreover, in vivo studies indicated that the CS-IGF-1C hydrogel promoted hP-MSC survival as visualized by BLI and markedly alleviated mouse colitis, which was possibly mediated by hP-MSC production of PGE 2 and interleukin-10 (IL-10) production by polarized M2 macrophages. Conclusions: The CS-IGF-1C hydrogel improved the engraftment of transplanted hP-MSCs, ameliorated inflammatory responses, and further promoted the functional and structural recovery of colitis through PGE 2 -mediated M2 macrophage polarization. Molecular imaging approaches and therapeutic strategies for hydrogel application provide a versatile platform for exploring the promising therapeutic potential of MSCs in the treatment of IBD.

Chitosan hydrogel-loaded MSC-derived extracellular vesicles promote skin rejuvenation by ameliorating the senescence of dermal fibroblasts

“…As a carrier system with high biocompatibility, biomaterials can improve the survival rate of transplanted cells and can also imitate the ECM microenvironment to provide an ideal niche for implanted cells and drugs [ 56 – 58 ]. CS have been deeply studied and widely applicated in the field of biomedicine as a natural polymer material with excellent properties [ 29 , 58 ]. Previous studies have confirmed that combining EVs from hP-MSC with injectable CS hydrogel can significantly retain EVs in the ischemic site of hind limbs.…”

Wogonin Strengthens the Therapeutic Effects of Mesenchymal Stem Cells in DSS‐Induced Colitis via Promoting IL‐10 Production

“…To overcome these hurdles, IFN-γ, TGF-β, IGF-1C, IL-1β, and PGE2 were applied to precondition MSCs before they were administered onto different experimental models, and pretreated MSCs showed an enhanced therapeutic effect, with different limitations [32][33][34][35][36]. All of these promising explorations encouraged us to search further alternatives.…”

Trio cooperates with Myh9 to regulate neural crest-derived craniofacial development

“…Von Kossa (1% silver nitrate) and total collagen staining (1% Sirius Red) were used to identify the mineralized bone. Immunohistochemical and immunofluorescence staining 72 , 73 was used to detect the phenotype differences and the expression of relevant molecules respectively. The following antibodies were used: anti-Trio (1:200, Santa Cruz, sc-28564), anti-Collagen I (1:300, Abcam, #ab21286), Sox-9 (1:100, Santa Cruz, sc-166505).…”