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Ziqi Yang, Yan Liu, Tian Zhou, Xiaowei Zhu, Chang He, Xialin Liu; IL-21 pre-stimulated MSC derived exosomes suppressing corneal neovascularization. Invest. Ophthalmol. Vis. Sci. 2019;60(9):940.
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Corneal neovascularization is a pathologic feature of the leading irreversible sight-threaten diseases and limited therapy is available. Recent studies have indicated that mesenchymal stem cells(MSCs) could suppress pathologic angiogenesis whereas the efficacy is conflict, which is possibly due to their various bio-functions at different diseased conditions especially under inflammatory insults. MSC-derived exosomes(MSC-exo) are considered to possess most functions of parental cells and take advantage of safe usage without cell infusion. In this case, our study aims to explore whether exosomes derived from IL-21 pre-stimulated MSCs could alleviate the ocular surface inflammation as well as the neovascularization and clarify the underlying mechanisms.
Exosomes were extracted from IL-21 pre-stimulated and unstimulated primary MSCs culture supernatant,while exosomes from L929 were taken as a control.All the exosomes were purified by ultracentrifugation and identified by scanning electron microscopy(SEM) analysis,nanoparticle tracking analysis(NTA) and western blot for surface biomarkers including CD63,CD9 and etc.Corneal angiogenesis model was established by alkali in C57BL/6 mice.Alkali-induced corneal angiogenesis mice received eye drops containing indicated exosomes respectively 4 times per day for 14 days.The corneal neovascularization was evaluated by slit lamp and IF staining for CD31.Exosomes were labeled with PKH-67 and the targeted cells were analyzed.The expression of miRNAs in corneas was detected by q-PCR.
Slit lamp images showed that treatment of IL-21 pre-stimulated or unstimulated MSC-exo suppressed the corneal angiogenesis remarkably, with the most effective role in IL-21 pre-stimulated MSC-exo.Hispathological images also revealed that the mice treated with IL-21 pre-stimulated MSC-exo presented less CD31 positive vessels than those with unstimulated MSC-exo. Interestingly, the PKH-67 labeled IL-21-MSC-exo was co-staining with CD31+ cells, indicating that the potential regulatory role of IL-21-MSC-exo in vascular endothelial cells. Among the detected miRNAs, we found the expression of miR-16 and miR125 was increased after the treatment of IL-21 pre-stimulated MSC-exo.
Our findings provided evidence that the exosomes derived from MSCs under IL-21 stimulation exerted a more potent anti-angiogenesis effect in corneal angiogenesis,optimizing the widely-used MSCs therapy.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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