Theranostics 2020; 10(17):7697-7709. doi:10.7150/thno.45434

Research Paper

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

Xiaocang Cao1#, Liyun Duan1#, Huixing Hou1, Yue Liu2, Shang Chen2, Shuaiqiang Zhang2, Yuanyuan Liu1, Chen Wang2, Xin Qi3, Na Liu2, Zhibo Han4,5, Dekui Zhang6, Zhong-Chao Han4,5, Zhikun Guo7✉, Qiang Zhao8✉, Zongjin Li2,7,8,9✉

1. Department of Hepato-Gastroenterology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China.
2. Nankai University School of Medicine, Tianjin, China.
3. Department of Cardiology, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, China.
4. Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, National Engineering Research Center of Cell Products, AmCellGene Co., Ltd., Tianjin China.
5. Jiangxi Engineering Research Center for Stem Cell, Shangrao, Jiangxi, China.
6. Gastroenterology Department, Lanzhou University Second Hospital, Gansu, China.
7. Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China.
8. The Key Laboratory of Bioactive Materials, Ministry of Education, the College of Life Science, Nankai University, Tianjin, China.
9. State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, China.
#These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Cao X, Duan L, Hou H, Liu Y, Chen S, Zhang S, Liu Y, Wang C, Qi X, Liu N, Han Z, Zhang D, Han ZC, Guo Z, Zhao Q, Li Z. IGF-1C hydrogel improves the therapeutic effects of MSCs on colitis in mice through PGE2-mediated M2 macrophage polarization. Theranostics 2020; 10(17):7697-7709. doi:10.7150/thno.45434. Available from http://www.thno.org/v10p7697.htm

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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 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.

Keywords: Inflammatory bowel disease (IBD), Mesenchymal stem cells (MSCs), M2 macrophage polarization, IGF-1C hydrogel, Prostaglandin E2 (PGE2)