# CCR2 overexpressing gingiva mesenchymal stem cells provide high intestinal regeneration in a rat model of ulcerative colitis

## TL;DR

Gingiva stem cells with increased CCR2 help heal inflamed colon tissue in a rat model of ulcerative colitis.

## Contribution

CCR2 overexpression on gingiva mesenchymal stem cells enhances their migration and regenerative effects in ulcerative colitis.

## Key findings

- CCR2+GMSCs migrated more effectively to inflamed colon tissue compared to GMSCs.
- CCR2+GMSCs improved mucosal integrity and reduced fibrosis and ulcers in UC rats.
- Both GMSCs and CCR2+GMSCs reduced IFN-γ and IL-17 secreting T lymphocytes in the colon.

## Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon. Mesenchymal stem cells (MSCs) are candidates for use in inflammatory diseases with their tissue regeneration and anti-inflammatory capabilities. Chemokine receptor overexpression on MSCs is an effective strategy for the migration of MSCs into inflammatory tissue in high amounts. In this study, the anti-inflammatory and regenerative effects of genetically CCR2 overexpressed gingiva MSCs (GMSCs) on the inflamed colon in UC were studied.

GMSCs were transduced with a lentiviral vector for CCR2 overexpression. The UC experimental model was induced with a single intrarectal administration of 4% w/w acetic acid. Colon tissues were analyzed for IFN or IL-17 secreting CD4+  T lymphocytes via flow cytometry and lymphocytic infiltration, fibrosis, and ulcers by histopathologic evaluation. Homing analysis of GMSCs was done by analyzing fluorescence intensity under the fluorescence microscope.

GMSCs and CCR2+GMSCs equally downregulated colonic IFN-γ or IL-17 secreting CD4+ T lymphocytes ratios compared to the untreated group (p < 0.05). Fluorescence intensity of labeled cells was significantly high in colon tissues of CCR2+GMSCs administered rats (61.2 ± 13.7%) compared to GMSCs administered rats (19.6 ± 9.8%) (p < 0.05). In addition, mucosal integrity significantly increased and fibrosis and ulcers notably decreased in CCR2+GMSCs administered rats compared to GMSCs administered rats (p < 0.05).

The overexpression of CCR2 on GMSCs increases migration to the inflammatory colon tissue, which has a high regenerative effect in UC. Overexpression of CCR2 on GMSCs may be an alternative to cellular therapies in UC.