IFN-γ promoted exosomes from mesenchymal stem cells to attenuate colitis via miR-125a and miR-125b

Abstract

Bone marrow mesenchymal stem cells (MSCs) have demonstrated therapeutic effects for colitis through immunomodulation and anti-inflammation. However, whether MSC-derived exosomes possessed the similar function remains unclear. In present study, exosomes were isolated from control and IFN-γ-primed MSCs and was verified by transmission electron microscope (TEM) and immunofluorescence staining. Administration of exosomes to mice significantly improved the disease activity index and histological score of colitis, and decreased the ratio of Th17 cells with elevated Treg cells ratio in mice colitis model. Exosomes from IFN-γ-primed MSCs showed superior therapeutic effects to colitis. Exosomes treatment inhibited Th17 differentiation in vitro, and exosomes from IFN-γ-primed MSCs showed higher inhibition efficacy. Mechanistically, exosomes treatment significantly decreased the expression of Stat3 and p-Stat3 to inhibit Th17 cells differentiation. IFN-γ pretreatment increased the level of miR-125a and miR-125b of exosomes, which directly targeted on Stat3, to repress Th17 cell differentiation. Moreover, combination of miR-125a and miR-125b agmior infusion also showed therapeutic effects for colitis, accompanied by decreased Th17 cell ratio. Collectively, this study demonstrates that IFN-γ treatment promoted exosomes from MSCs to attenuate colitis through increasing the level of miR-125a and miR-125b, which binding on 3′-UTR of Stat3 to repress Th17 cell differentiation. This study provides a new approach of exocytosis on the treatment of colitis.

Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

“…Although simultaneous increases in Th17 and Treg by treatment with MSC exosomes have been reported [49], Th17 cells and Tregs are generally considered to be in a competitive relationship. Indeed, MSC exosomes have been reported to promote Tregs while suppressing the polarization of TH17 cells by SphK1-mediated SP1 enrichment in an aplastic anemia (AA) model [50] and increase miR-125a and miR-125b expression in an experimental colitis model [51]. MSC exosomes also suppress excessive allergic inflammation.…”

Mesenchymal stem cell-derived exosomes inhibit Aβ1-42 induced microglia polarization by TLR2/MYD88/NF-κB pathway

“…For the use of mesenchymal stem cell exosomes, we used exosomes extracted from untreated simple cells. In the current study, some experimenters also used exosomes obtained after intervention with other substances, such as interferon gamma [47][48][49]. As with other related secretionpromoting substances, whether the use of activated exosomes is more bene cial to the treatment of diseases remains to be veri ed.…”

Exosomes Secreted by Mesenchymal Stem Cells Induce Immune Tolerance to Kidney Transplantation via Transporting lncRNA DANCR

“…The adherent cells were removed 48 h later. After the adherent cells reached 90% fusion, the adherent cells were treated with trypsin [19]. Mice were raised in the Animal Center of Zhengzhou University.…”

“…TEM was conducted to observe the morphology of BMMSC-Ex using a Tecnai™ transmission electron microscope (FEI, USA). Before photography, BMMSC-Ex was suspended in 2.5% glutaraldehyde and loaded on the copper grids [19].…”