Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina.
Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina.
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施用的骨髓间充质干细胞细胞外囊泡在视网膜中的摄取和分布。
作者:
Mathew B;Torres LA;Gamboa Acha L;Tran S;Liu A;Patel R;Chennakesavalu M;Aneesh A;Huang CC;Feinstein DL;Mehraeen S;Ravindran S;Roth S
Cell replacement therapy using mesenchymal (MSC) and other stem cells has been evaluated for diabetic retinopathy and glaucoma. This approach has significant limitations, including few cells integrated, aberrant growth, and surgical complications. Mesenchymal Stem Cell Exosomes/Extracellular Vesicles (MSC EVs), which include exosomes and microvesicles, are an emerging alternative, promoting immunomodulation, repair, and regeneration by mediating MSC’s paracrine effects. For the clinical translation of EV therapy, it is important to determine the cellular destination and time course of EV uptake in the retina following administration. Here, we tested the cellular fate of EVs using in vivo rat retinas, ex vivo retinal explant, and primary retinal cells. Intravitreally administered fluorescent EVs were rapidly cleared from the vitreous. Retinal ganglion cells (RGCs) had maximal EV fluorescence at 14 days post administration, and microglia at 7 days. Both in vivo and in the explant model, most EVs were no deeper than the inner nuclear layer. Retinal astrocytes, microglia, and mixed neurons in vitro endocytosed EVs in a dose-dependent manner. Thus, our results indicate that intravitreal EVs are suited for the treatment of retinal diseases affecting the inner retina. Modification of the EV surface should be considered for maintaining EVs in the vitreous for prolonged delivery.
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影响因子:
--
作者:
Gutkin A;Uziel O;Beery E;Nordenberg J;Pinchasi M;Goldvaser H;Henick S;Goldberg M;Lahav M
通讯作者:
Lahav M
DOI:
10.1038/s41433-020-0895-z
发表时间:
2020-11
期刊:
Eye (London, England)
影响因子:
--
作者:
Adamis AP;Brittain CJ;Dandekar A;Hopkins JJ
通讯作者:
Hopkins JJ
影响因子:
6.7
作者:
Chugh PE;Sin SH;Ozgur S;Henry DH;Menezes P;Griffith J;Eron JJ;Damania B;Dittmer DP
通讯作者:
Dittmer DP
DOI:
10.1007/978-3-030-49844-3_4
发表时间:
2021-01-01
期刊:
PROTEIN KINASE-MEDIATED DECISIONS BETWEEN LIFE AND DEATH
影响因子:
--
作者:
Engin, Atilla
通讯作者:
Engin, Atilla
影响因子:
3.4
作者:
Costes, SV;Daelemans, D;Lockett, S
通讯作者:
Lockett, S