Available online 5 July 2022, 104573

1. PI3Kγ-/- mice showed less improvement than the wild-type mice after MSCs transplantation.

MSCs worsen the intestinal microecological presentation in PI3Kγ-/- mice

Immune interference from MSCs contributes to the deterioration of presentations invovled in colitis.

Considering the possible interaction between mesenchymal stem cells (MSCs) and PI3Kγ-associated drugs, we evaluated the efficacy and action mechanism of MSCs in the treatment of colitis in PI3Kγ-/- mice. Trinitro-benzene-sulfonic acid enema was used to create a colitis model, and MSCs were transplanted through the caudal vein to treat colitis in wild-type and PI3Kγ-/- mice. We sequenced microbial 16S rRNA genes in the colonic mucosa of PI3Kγ-/- and wild-type mice and quantified colonic IgA, IL-2, IL-10, IL-17A, occludin, and serum IgA. MSC transplantation led to a more serious reduction in the weight of trinitro-benzene-sulfonic acid-administered PI3Kγ-/- mice than that in wild-type mice. The disease activity index, pathological scoring, number of taxa in the colon, Berger–Parker index, I-index, proportion of Proteobacteria, and IgA level in the blood were higher in PI3Kγ-/- mice than in wild-type mice after MSC transplantation. The occludin and IL-10 levels in the colon tissues decreased before and after MSC transplantation in PI3Kγ-/- mice, whereas they were increased in wild-type mice The IL-17 level decreased in both wild-type and PI3Kγ-/- mice, with knockout mice showing a greater decrease. Therefore, MSC transplantation in PI3Kγ-/- mice led to increased numbers of exogenous pathogenic microorganisms and enhanced colitis that was difficult to relieve.

mesenchymal stem cell transplantation

PI3Kγ pathway

occludin

phosphoinositide 3-kinase-γ

inflammatory bowel disease

trinitro-benzene-sulfonic acid

Ribosomal Database Project

phosphate buffer saline

improvement rate of rate of weight gain

disease activity index

improvement rate of disease activity index

improvement rate of pathological scoring

minimum Essential Medium-α

© 2022 Published by Elsevier Inc.