A Novel Approach to Deliver Therapeutic Extracellular Vesicles Directly into the Mouse Kidney via Its Arterial Blood Supply
Diseases of the kidney contribute a significant morbidity and mortality burden on society. Localized delivery of therapeutics directly into the kidney, via its arterial blood supply, has the potential to enhance their therapeutic efficacy while limiting side effects associated with conventional syst...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/4/937 |
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| author | Mujib Ullah Daniel D. Liu Sravanthi Rai Mehdi Razavi Jeff Choi Jing Wang Waldo Concepcion Avnesh S. Thakor |
| author_facet | Mujib Ullah Daniel D. Liu Sravanthi Rai Mehdi Razavi Jeff Choi Jing Wang Waldo Concepcion Avnesh S. Thakor |
| author_sort | Mujib Ullah |
| collection | DOAJ |
| description | Diseases of the kidney contribute a significant morbidity and mortality burden on society. Localized delivery of therapeutics directly into the kidney, via its arterial blood supply, has the potential to enhance their therapeutic efficacy while limiting side effects associated with conventional systemic delivery. Targeted delivery in humans is feasible given that we can access the renal arterial blood supply using minimally invasive endovascular techniques and imaging guidance. However, there is currently no described way to reproduce or mimic this approach in a small animal model. Here, we develop in mice a reproducible microsurgical technique for the delivery of therapeutics directly into each kidney, via its arterial blood supply. Using our technique, intra-arterially (IA) injected tattoo dye homogenously stained both kidneys, without staining any other organ. Survival studies showed no resulting mortality or iatrogenic kidney injury. We demonstrate the therapeutic potential of our technique in a mouse model of cisplatin-induced acute kidney injury (AKI). IA injection of mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) successfully reversed AKI, with reduced physiological and molecular markers of kidney injury, attenuated inflammation, and restoration of proliferation and regeneration markers. This reproducible delivery technique will allow for further pre-clinical translational studies investigating other therapies for the treatment of renal pathologies. |
| first_indexed | 2024-03-10T20:32:30Z |
| format | Article |
| id | doaj.art-f58b85f4fb684615892cae1dcca7d6ac |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T20:32:30Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f58b85f4fb684615892cae1dcca7d6ac2023-11-19T21:18:03ZengMDPI AGCells2073-44092020-04-019493710.3390/cells9040937A Novel Approach to Deliver Therapeutic Extracellular Vesicles Directly into the Mouse Kidney via Its Arterial Blood SupplyMujib Ullah0Daniel D. Liu1Sravanthi Rai2Mehdi Razavi3Jeff Choi4Jing Wang5Waldo Concepcion6Avnesh S. Thakor7Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University School of Medicine, Palo Alto, CA 94304, USAInterventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University School of Medicine, Palo Alto, CA 94304, USAInterventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University School of Medicine, Palo Alto, CA 94304, USAInterventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University School of Medicine, Palo Alto, CA 94304, USAInterventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University School of Medicine, Palo Alto, CA 94304, USAInterventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University School of Medicine, Palo Alto, CA 94304, USADepartment of Surgery, Stanford University, Stanford, CA 94305, USAInterventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University School of Medicine, Palo Alto, CA 94304, USADiseases of the kidney contribute a significant morbidity and mortality burden on society. Localized delivery of therapeutics directly into the kidney, via its arterial blood supply, has the potential to enhance their therapeutic efficacy while limiting side effects associated with conventional systemic delivery. Targeted delivery in humans is feasible given that we can access the renal arterial blood supply using minimally invasive endovascular techniques and imaging guidance. However, there is currently no described way to reproduce or mimic this approach in a small animal model. Here, we develop in mice a reproducible microsurgical technique for the delivery of therapeutics directly into each kidney, via its arterial blood supply. Using our technique, intra-arterially (IA) injected tattoo dye homogenously stained both kidneys, without staining any other organ. Survival studies showed no resulting mortality or iatrogenic kidney injury. We demonstrate the therapeutic potential of our technique in a mouse model of cisplatin-induced acute kidney injury (AKI). IA injection of mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) successfully reversed AKI, with reduced physiological and molecular markers of kidney injury, attenuated inflammation, and restoration of proliferation and regeneration markers. This reproducible delivery technique will allow for further pre-clinical translational studies investigating other therapies for the treatment of renal pathologies.https://www.mdpi.com/2073-4409/9/4/937locoregional deliveryintra-arterial deliverytargeted therapymicrosurgeryacute kidney injurymesenchymal stromal cells |
| spellingShingle | Mujib Ullah Daniel D. Liu Sravanthi Rai Mehdi Razavi Jeff Choi Jing Wang Waldo Concepcion Avnesh S. Thakor A Novel Approach to Deliver Therapeutic Extracellular Vesicles Directly into the Mouse Kidney via Its Arterial Blood Supply Cells locoregional delivery intra-arterial delivery targeted therapy microsurgery acute kidney injury mesenchymal stromal cells |
| title | A Novel Approach to Deliver Therapeutic Extracellular Vesicles Directly into the Mouse Kidney via Its Arterial Blood Supply |
| title_full | A Novel Approach to Deliver Therapeutic Extracellular Vesicles Directly into the Mouse Kidney via Its Arterial Blood Supply |
| title_fullStr | A Novel Approach to Deliver Therapeutic Extracellular Vesicles Directly into the Mouse Kidney via Its Arterial Blood Supply |
| title_full_unstemmed | A Novel Approach to Deliver Therapeutic Extracellular Vesicles Directly into the Mouse Kidney via Its Arterial Blood Supply |
| title_short | A Novel Approach to Deliver Therapeutic Extracellular Vesicles Directly into the Mouse Kidney via Its Arterial Blood Supply |
| title_sort | novel approach to deliver therapeutic extracellular vesicles directly into the mouse kidney via its arterial blood supply |
| topic | locoregional delivery intra-arterial delivery targeted therapy microsurgery acute kidney injury mesenchymal stromal cells |
| url | https://www.mdpi.com/2073-4409/9/4/937 |
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