Intercellular adhesion molecule-1 enhances the therapeutic effects of MSCs in a dextran sulfate sodium-induced colitis models by promoting MSCs homing to murine colons and spleens

Abstract

Background To investigate the therapeutic effect of intercellular adhesion molecule (ICAM)-1-modified mesenchymal stem cells (MSCs) in a mouse model of inflammatory bowel disease (IBD) induced by dextran sulfate sodium. Methods Primary MSCs and ICAM-1-overexpressing MSCs (C3 cells) were generated in vitro. The IBD mouse model was induced with drinking water containing dextran sulfate sodium for 7 days. For stem cell therapy, mice were randomly assigned to six experimental groups: the control group, IBD group, primary MSC group, C3 group, C3-vector group, and C3-ICAM-1 group. Mice were given a single injection of 1 × 10 6 primary MSCs or gene-modified MSCs via the tail vein on day 3 of DDS administration. The general conditions of the mice in each group were observed. Additionally, the pathological changes in the colon were observed and scored. Primary MSCs and gene-modified MSCs were stained with the fluorescent dye CM-DIL before injection into the tail vein of mice. The distribution of infused cells in IBD mice was observed in frozen sections. Mechanistically, the polarization of Th1, Th2, Th17, and regulatory T cells (Tregs) in the spleen was determined by flow cytometry. Moreover, the mRNA expression levels of IBD-related immune factors in splenocytes were measured by quantitative PCR. Results A single injection of MSCs promoted general recovery and reduced pathological damage in IBD mice. Additionally, ICAM-1-overexpressing MSCs had stronger therapeutic effects than ICAM-1 low MSCs. Furthermore, the in vivo distribution analysis results indicated that a higher number of ICAM-1-overexpressing MSCs homed to the colon and spleen of IBD mice. Moreover, the delivery of ICAM-1 overexpressing MSCs decreased the numbers of Th1 and Th17 cells but increased the number of Tregs in the spleen of IBD mice. The quantitative PCR analysis results revealed that an infusion of ICAM-1-overexpressing MSCs influenced the expression of spleen-derived immune factors by remarkably reducing the mRNA levels of IFN-γ and IL-17A and increasing the mRNA level of Foxp3. Conclusions Our results demonstrate that ICAM-1-modified mesenchymal stem cells (MSCs) remarkably alleviate inflammatory damage in IBD mice by promoting MSC homing to the target and immune organs. The findings suggest that ICAM-1 is required to maintain the therapeutic effects of MSCs in IBD treatment and identified a novel role of ICAM-1 in inflammatory diseases. Electronic supplementary material The online version of this article (10.1186/s13287-019-1384-9) contains supplementary material, which is available to authorized users.

GVHD-derived plasma as a priming strategy of mesenchymal stem cells

“…Recently, Tang and colleagues demonstrated that MSCs overexpressing ICAM-1 prolonged the survival of mice with GVHD [39]. In accordance with such observation, MSCs overexpressing ICAM-1 were shown to possess stronger therapeutic effects than ICAM-1-low MSCs in a mouse model of inflammatory bowel disease [40].…”

Potential methods for improving the efficacy of mesenchymal stem cells in the treatment of inflammatory bowel diseases

“…63 And they demonstrated that CXCR4-IL-35-MSCs remarkably strengthened the immunomodulatory activity of BM-MSCs through the simultaneous suppression of Th17 cells and expansion of Tregs. Li et al 64 obtained similar results by upregulating intercellular adhesion molecule (ICAM)-1 in the mouse MSC cell line. It has been demonstrated that ICAM-1 is involved in the regulation of immune responses, mediating cell differentiation and development, and is closely related to lymphocyte homing and recycling.…”

“…65 They found that transplantation of ICAM-1overexpressing MSCs not only alleviated colonic inflammation and regulated T cell subpopulations more obviously, but also mediated a higher number of MSCs homing to the colon and spleen of the mouse model of IBD. 64 MicroRNAs are a family of endogenous non-coding RNAs, consisting of 22-24 bp in length. They silence gene expression post-transcriptionally by binding to the 3′ untranslated region of mRNA.…”

Genetic Engineering as a Strategy to Improve the Therapeutic Efficacy of Mesenchymal Stem/Stromal Cells in Regenerative Medicine

“…In a mouse model of inflammatory bowel disease (IBD) induced by sodium dextran sulfate, increased expression of the Intercellular Adhesion Molecule (ICAM)-1 by MSCs have been shown to alleviate inflammatory damage in IBD mice, reducing colon shortening to levels closer to the control without IBD, in addition to halving the number of inflammatory cells when compared to the untreated IBD group. Moreover, ICAM-1 also stimulated the migration of modified MSC to the affected colon (Li et al, 2019).…”