Internal medicine

Pathology

Biotechnology

Bioluminescence imaging

Mesenchymal stem cell

In vivo

Inflammatory bowel disease

Disease

Macrophage

Biology

Gene

Luciferase

Chemistry

In vitro

Immunology

Colitis

Macrophage polarization

Prostaglandin E2

M2 Macrophage

Transfection

Cancer research

Biochemistry

Medicine

Pharmacology

Theranostics

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 E2 (PGE2) 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 PGE2 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 PGE2 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 PGE2-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.

IGF-1C hydrogel improves the therapeutic effects of MSCs on colitis in mice through PGE<sub>2</sub>-mediated M2 macrophage polarization

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

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