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Bioactive extracellular vesicles from a subset of endothelial progenitor cells rescue retinal ischemia and neurodegeneration
Kyle V. Marra, … , Susumu Sakimoto, Martin Friedlander
Kyle V. Marra, … , Susumu Sakimoto, Martin Friedlander
Published May 31, 2022
Citation Information: JCI Insight. 2022;7(12):e155928. https://doi.org/10.1172/jci.insight.155928.
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Research Article Ophthalmology Vascular biology

Bioactive extracellular vesicles from a subset of endothelial progenitor cells rescue retinal ischemia and neurodegeneration

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Abstract

Disruption of the neurovascular unit (NVU) underlies the pathophysiology of various CNS diseases. One strategy to repair NVU dysfunction uses stem/progenitor cells to provide trophic support to the NVU’s functionally coupled and interdependent vasculature and surrounding CNS parenchyma. A subset of endothelial progenitor cells, endothelial colony-forming cells (ECFCs) with high expression of the CD44 hyaluronan receptor (CD44hi), provides such neurovasculotrophic support via a paracrine mechanism. Here, we report that bioactive extracellular vesicles from CD44hi ECFCs (EVshi) are paracrine mediators, recapitulating the effects of intact cell therapy in murine models of ischemic/neurodegenerative retinopathy; vesicles from ECFCs with low expression levels of CD44 (EVslo) were ineffective. Small RNA sequencing comparing the microRNA cargo from EVshi and EVslo identified candidate microRNAs that contribute to these effects. EVshi may be used to repair NVU dysfunction through multiple mechanisms to stabilize hypoxic vasculature, promote vascular growth, and support neural cells.

Authors

Kyle V. Marra, Edith Aguilar, Guoqin Wei, Ayumi Usui-Ouchi, Yoichiro Ideguchi, Susumu Sakimoto, Martin Friedlander

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Figure 5

EVshi improves photoreceptor density in inherited retinal degeneration mice.

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EVshi improves photoreceptor density in inherited retinal degeneration m...
(A and B) Immunohistochemistry for cone- and rod-specific markers on RD10 retinas treated P14 and harvested P28 demonstrated photoreceptor preservation by EVshi. Retinal cross sections were stained for recoverin (in red) in A and for opsin red/green (in green) in B with Hoechst 3342 nuclear staining (in blue). (C) Quantification of cone photoreceptor density. One-way ANOVA with Tukey’s analysis; n = 6 eyes for each group. Scale bars: 50 μm. *P < 0.05, **P < 0.01, ****P < 0.0001.

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