Embryonic stem cell-derived extracellular vesicles promote the recovery of kidney injury

Abstract Background Embryonic stem cell-derived extracellular vesicles (ESC-EVs) possess therapeutic potential for a variety of diseases and are considered as an alternative of ES cells. Acute kidney injury (AKI) is a common acute and severe disease in clinical practice, which seriously threatens hu...

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Main Authors: Lu Yu, Siying Liu, Chen Wang, Chuanyu Zhang, Yajie Wen, Kaiyue Zhang, Shang Chen, Haoyan Huang, Yue Liu, Lingling Wu, Zhongchao Han, Xiangmei Chen, Zongjin Li, Na Liu
Format: Article
Language:English
Published: BMC 2021-07-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13287-021-02460-0
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author Lu Yu
Siying Liu
Chen Wang
Chuanyu Zhang
Yajie Wen
Kaiyue Zhang
Shang Chen
Haoyan Huang
Yue Liu
Lingling Wu
Zhongchao Han
Xiangmei Chen
Zongjin Li
Na Liu
author_facet Lu Yu
Siying Liu
Chen Wang
Chuanyu Zhang
Yajie Wen
Kaiyue Zhang
Shang Chen
Haoyan Huang
Yue Liu
Lingling Wu
Zhongchao Han
Xiangmei Chen
Zongjin Li
Na Liu
author_sort Lu Yu
collection DOAJ
description Abstract Background Embryonic stem cell-derived extracellular vesicles (ESC-EVs) possess therapeutic potential for a variety of diseases and are considered as an alternative of ES cells. Acute kidney injury (AKI) is a common acute and severe disease in clinical practice, which seriously threatens human life and health. However, the roles and mechanisms of ESC-EVs on AKI remain unclear. Methods In this study, we evaluated the effects of ESC-EVs on physiological repair and pathological repair using murine ischemia-reperfusion injury-induced AKI model, the potential mechanisms of which were next investigated. EVs were isolated from ESCs and EVs derived from mouse fibroblasts as therapeutic controls. We then investigated whether ESC-EVs can restore the structure and function of the damaged kidney by promoting physiological repair and inhibiting the pathological repair process after AKI in vivo and in vitro. Results We found that ESC-EVs significantly promoted the recovery of the structure and function of the damaged kidney. ESC-EVs increased the proliferation of renal tubular epithelial cells, facilitated renal angiogenesis, inhibited the progression of renal fibrosis, and rescued DNA damage caused by ischemia and reperfusion after AKI. Finally, we found that ESC-EVs play a therapeutic effect by activating Sox9+ cells. Conclusions ESC-EVs significantly promote the physiological repair and inhibit the pathological repair after AKI, enabling restoration of the structure and function of the damaged kidney. This strategy might emerge as a novel therapeutic strategy for ESC clinical application.
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spelling doaj.art-d2ea21aef72e4265bd621b38b6ed45e52022-12-21T22:45:18ZengBMCStem Cell Research & Therapy1757-65122021-07-0112111710.1186/s13287-021-02460-0Embryonic stem cell-derived extracellular vesicles promote the recovery of kidney injuryLu Yu0Siying Liu1Chen Wang2Chuanyu Zhang3Yajie Wen4Kaiyue Zhang5Shang Chen6Haoyan Huang7Yue Liu8Lingling Wu9Zhongchao Han10Xiangmei Chen11Zongjin Li12Na Liu13School of Medicine, Nankai UniversitySchool of Medicine, Nankai UniversitySchool of Medicine, Nankai UniversitySchool of Medicine, Nankai UniversitySchool of Medicine, Nankai UniversitySchool of Medicine, Nankai UniversitySchool of Medicine, Nankai UniversitySchool of Medicine, Nankai UniversitySchool of Medicine, Nankai UniversityState Key Laboratory of Kidney Diseases, Chinese PLA General HospitalBeijing Engineering Laboratory of Perinatal Stem Cells, Beijing Institute of Health and Stem Cells, Health & Biotech Co.State Key Laboratory of Kidney Diseases, Chinese PLA General HospitalSchool of Medicine, Nankai UniversitySchool of Medicine, Nankai UniversityAbstract Background Embryonic stem cell-derived extracellular vesicles (ESC-EVs) possess therapeutic potential for a variety of diseases and are considered as an alternative of ES cells. Acute kidney injury (AKI) is a common acute and severe disease in clinical practice, which seriously threatens human life and health. However, the roles and mechanisms of ESC-EVs on AKI remain unclear. Methods In this study, we evaluated the effects of ESC-EVs on physiological repair and pathological repair using murine ischemia-reperfusion injury-induced AKI model, the potential mechanisms of which were next investigated. EVs were isolated from ESCs and EVs derived from mouse fibroblasts as therapeutic controls. We then investigated whether ESC-EVs can restore the structure and function of the damaged kidney by promoting physiological repair and inhibiting the pathological repair process after AKI in vivo and in vitro. Results We found that ESC-EVs significantly promoted the recovery of the structure and function of the damaged kidney. ESC-EVs increased the proliferation of renal tubular epithelial cells, facilitated renal angiogenesis, inhibited the progression of renal fibrosis, and rescued DNA damage caused by ischemia and reperfusion after AKI. Finally, we found that ESC-EVs play a therapeutic effect by activating Sox9+ cells. Conclusions ESC-EVs significantly promote the physiological repair and inhibit the pathological repair after AKI, enabling restoration of the structure and function of the damaged kidney. This strategy might emerge as a novel therapeutic strategy for ESC clinical application.https://doi.org/10.1186/s13287-021-02460-0Embryonic stem cell (ESC)Extracellular vesicles (EVs)Acute kidney injury (AKI)Physiological repairPathological repair
spellingShingle Lu Yu
Siying Liu
Chen Wang
Chuanyu Zhang
Yajie Wen
Kaiyue Zhang
Shang Chen
Haoyan Huang
Yue Liu
Lingling Wu
Zhongchao Han
Xiangmei Chen
Zongjin Li
Na Liu
Embryonic stem cell-derived extracellular vesicles promote the recovery of kidney injury
Stem Cell Research & Therapy
Embryonic stem cell (ESC)
Extracellular vesicles (EVs)
Acute kidney injury (AKI)
Physiological repair
Pathological repair
title Embryonic stem cell-derived extracellular vesicles promote the recovery of kidney injury
title_full Embryonic stem cell-derived extracellular vesicles promote the recovery of kidney injury
title_fullStr Embryonic stem cell-derived extracellular vesicles promote the recovery of kidney injury
title_full_unstemmed Embryonic stem cell-derived extracellular vesicles promote the recovery of kidney injury
title_short Embryonic stem cell-derived extracellular vesicles promote the recovery of kidney injury
title_sort embryonic stem cell derived extracellular vesicles promote the recovery of kidney injury
topic Embryonic stem cell (ESC)
Extracellular vesicles (EVs)
Acute kidney injury (AKI)
Physiological repair
Pathological repair
url https://doi.org/10.1186/s13287-021-02460-0
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