Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina
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 Vesicle...
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| Format: | Article |
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MDPI AG
2021-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/4/730 |
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| author | Biji Mathew Leianne A. Torres Lorea Gamboa Acha Sophie Tran Alice Liu Raj Patel Mohansrinivas Chennakesavalu Anagha Aneesh Chun-Chieh Huang Douglas L. Feinstein Shafigh Mehraeen Sriram Ravindran Steven Roth |
| author_facet | Biji Mathew Leianne A. Torres Lorea Gamboa Acha Sophie Tran Alice Liu Raj Patel Mohansrinivas Chennakesavalu Anagha Aneesh Chun-Chieh Huang Douglas L. Feinstein Shafigh Mehraeen Sriram Ravindran Steven Roth |
| author_sort | Biji Mathew |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T12:54:05Z |
| format | Article |
| id | doaj.art-490baac648564bd5b95c0da485296da9 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T12:54:05Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-490baac648564bd5b95c0da485296da92023-11-21T12:02:17ZengMDPI AGCells2073-44092021-03-0110473010.3390/cells10040730Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in RetinaBiji Mathew0Leianne A. Torres1Lorea Gamboa Acha2Sophie Tran3Alice Liu4Raj Patel5Mohansrinivas Chennakesavalu6Anagha Aneesh7Chun-Chieh Huang8Douglas L. Feinstein9Shafigh Mehraeen10Sriram Ravindran11Steven Roth12Department of Anesthesiology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Anesthesiology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Anesthesiology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Anesthesiology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Anesthesiology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Anesthesiology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Anesthesiology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Anesthesiology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Oral Biology, College of Dentistry, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Anesthesiology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Chemical Engineering, College of Engineering, University of Illinois at Chicago, Chicago, IL 60607, USADepartment of Oral Biology, College of Dentistry, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Anesthesiology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USACell 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.https://www.mdpi.com/2073-4409/10/4/730astrocytesexosomesextracellular vesiclesin vivo imagingischemiamicroglia |
| spellingShingle | Biji Mathew Leianne A. Torres Lorea Gamboa Acha Sophie Tran Alice Liu Raj Patel Mohansrinivas Chennakesavalu Anagha Aneesh Chun-Chieh Huang Douglas L. Feinstein Shafigh Mehraeen Sriram Ravindran Steven Roth Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina Cells astrocytes exosomes extracellular vesicles in vivo imaging ischemia microglia |
| title | Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina |
| title_full | Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina |
| title_fullStr | Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina |
| title_full_unstemmed | Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina |
| title_short | Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina |
| title_sort | uptake and distribution of administered bone marrow mesenchymal stem cell extracellular vesicles in retina |
| topic | astrocytes exosomes extracellular vesicles in vivo imaging ischemia microglia |
| url | https://www.mdpi.com/2073-4409/10/4/730 |
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