Available online 5 July 2022, 104573
Highlights•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.
AbstractConsidering 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.
Keywordsmesenchymal stem cell transplantation
PI3Kγ pathway
occludin
AbbreviationsPI3Kphosphoinositide 3-kinase-γ
IBDinflammatory bowel disease
TNBStrinitro-benzene-sulfonic acid
RDFRibosomal Database Project
PBSphosphate buffer saline
WGRimprovement rate of rate of weight gain
DAIdisease activity index
I-DAIimprovement rate of disease activity index
PCimprovement rate of pathological scoring
α-MEMminimum Essential Medium-α
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