Anti-VCAM 1 Antibody-Coated Mesenchymal Stromal Cells Attenuate Experimental Colitis via Immunomodulation
Qianqian Chen, Yi Li, Zheng Chen, Haitao Du, Jun Wan
(Department of Gastroenterology, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China (mainland))
Med Sci Monit 2019; 25:4457-4468
The treatment of inflammatory bowel disease (IBD) is still not satisfactory and novel technologies are clinically needed. This study aimed to examine the effect of mesenchymal stromal cells (MSCs) coated with the anti-vascular cell adhesion molecule 1 (VCAM 1) antibody on experimental colitis.
MATERIAL AND METHODS: The antibody was coated onto the MSCs isolated from male BALB/C mice to generate anti-VCAM 1 antibody-coated MSC (V-MSC). The Transwell assay was used to detect migration rate. 2,4,6-trinitrobenzenesulfonic acid (TNBS) was used to generate experimental colitis. MSCs were injected intravenously into experimental models. Weight changes, disease activity index, and histological changes were evaluated. The SRY gene were used for cell tracking. Expression of Ki67 and claudin 1 was used to measure local repair using immunohistochemistry. T helper (Th)1, Th2, Th17, and T regulatory cells were counted.
RESULTS: V-MSCs were successfully generated through coating MSCs with VCAM1 antibody. Analysis showed that the V-MSCs had similar surface types and differentiation as uncoated MSCs. Transwell assays showed that V-MSCs had higher migration rate than MSCs. After injection of V-MSCs, the expression of the SRY gene was enhanced in diseased colon and all indices (including weight changes, DAI score, histological changes, and the expressions of Ki67 and claudin 1) recovered rapidly. The ratio of proinflammatory Th1 and Th17 cells decreased, but the ratio of anti-inflammatory Th2 and Treg cells increased after the treatment.
CONCLUSIONS: V-MSCs enhance homing and modulating immune balance in the experimental colitis, suggesting that they are potentially useful for treating inflammatory bowel disease or other immune diseases.
Keywords: Cell Adhesion Molecules, Immunomodulation, Inflammatory Bowel Diseases, mesenchymal stromal cells