Dataset Information

Exosomes from mesenchymal stromal cells reduce murine colonic inflammation via a macrophage-dependent mechanism

ABSTRACT: Conventional treatments for inflammatory bowel disease (IBD) have multiple potential side effects. Therefore, alternative treatments are desperately needed. In the present study, we proposed a new therapeutic tool for the treatment of IBD in murine pre-clinical models by using MSC-Exos. We demonstrated that the infused MSC-Exos are immunotolerated by the host, which is convenient for a future clinical application of MSC-Exos in IBD. To understand the molecular basis mediating the anticolitic benefit of MSC-Exos, we performed proteomic analysis using iTRAQ technology to detect the protein expression profiles in MSC-Exos and the corresponding supernatants from their parent cell MSCs. Proteomic analysis revealed that MSC-Exos were enriched in proteins involved in regulating multiple biological processes associated with the anti-colitic benefit of MSC-Exos. Particularly, metallothionein-2 in MSC-Exos was required for the suppression of inflammatory responses in macrophages. Taken together, MSC-Exos are critical regulators of inflammatory responses and may be promising candidates for IBD treatment.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Ping Lan

LAB HEAD: Ping Lan

PROVIDER: PXD015386 | Pride | 2020-05-27

REPOSITORIES: Pride

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Exosomes from mesenchymal stromal cells reduce murine colonic inflammation via a macrophage-dependent mechanism.

Liu Huashan H Liang Zhenxing Z Wang Fengwei F Zhou Chi C Zheng Xiaobin X Hu Tuo T He Xiaowen X Wu Xianrui X Lan Ping P

JCI insight 20191219 24

Conventional treatments for inflammatory bowel disease (IBD) have multiple potential side effects. Therefore, alternative treatments are desperately needed. This work demonstrated that systemic administration of exosomes from human bone marrow-derived mesenchymal stromal cells (MSC-Exos) substantially mitigated colitis in various models of IBD. MSC-Exos treatment downregulated inflammatory responses, maintained intestinal barrier integrity, and polarized M2b macrophages but did not favor intesti ...[more]

PMID: 31689240

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Project description:Limbal stem cells including epithelial and stromal/Mesenchymal stem cells that contribute to sustained corneal homeostasis, maintain their ability to act as self-renewal progenitor cells by virtue of their limbal niche and intercellular communication. Extracellular vehicles (EVs), including exosomes (Exos), are important paracrine mediators through their cargo transfer for intercellular communication in various stem cell niches. Previously we have shown the differential cargos and regulatory roles of limbal stromal cell (LSC)-derived Exos, in limbal epithelial cells (LEC) in normal (N) and diabetic (DM) limbal niche. In the present study, to have a comprehensive knowledge of reciprocal LEC-LSC crosstalk, we investigated the proteomics and miRNA profile of exosomes derived from LEC and their regulatory roles in LSC in N and DM limbus. Our study showed wound healing and proliferation rates in primary N-LSC were significantly enhanced upon treatment by normal LEC-derived Exos (N-Exos), but not by diabetic Exos (DM-Exos). Further, N-Exos treated LSC showed downregulation of keratocyte markers, ALDH3A1 and lumican, but not keratocan, and upregulation of MSC markers, CD105, CD90, and CD73 compared to the DM-Exos treated LSC. Using next generation sequencing (NGS) and proteomics analysis, we revealed some miRNAs and proteins in the Exos that affect the cellular crosstalk and the function of the cornea. We also documented differences in DM vs. normal LEC-derived Exo’s cargos. Overall, DM-Exos have less effect on LSC proliferation, wound healing, and stem cell maintenance than N-Exos, likely by transferring their cargo proteins and/or regulatory miRNAs targeting cell cycle, ERK/MAPK, TGF-β, EMT, PI3K-Akt-mTOR signaling molecules. This suggests that the small RNA and protein cargo differences in DM vs. N LEC-derived Exos could contribute to the disease state. Our study revealed a complex contribution of Exos to health and diabetic state of corneal homeostasis and suggests the potential of EV therapeutics for diabetic cornea regenerative medicine

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