Frontiers in Cell and Developmental Biology (Feb 2022)
Human Amniotic Epithelial Cells and Their Derived Exosomes Protect Against Cisplatin-Induced Acute Kidney Injury Without Compromising Its Antitumor Activity in Mice
- Xin Kang,
- Xin Kang,
- Xin Kang,
- Ying Chen,
- Ying Chen,
- Ying Chen,
- Ying Chen,
- Ying Chen,
- Xiaohong Xin,
- Xiaohong Xin,
- Xiaohong Xin,
- Menghan Liu,
- Menghan Liu,
- Menghan Liu,
- Yuan Ma,
- Yuan Ma,
- Yuan Ma,
- Yifei Ren,
- Yifei Ren,
- Yifei Ren,
- Jing Ji,
- Jing Ji,
- Jing Ji,
- Qi Yu,
- Qi Yu,
- Qi Yu,
- Lei Qu,
- Lei Qu,
- Lei Qu,
- Suxia Wang,
- Gang Liu,
- Gang Liu,
- Gang Liu,
- Gang Liu,
- Gang Liu,
- Chengang Xiang,
- Chengang Xiang,
- Chengang Xiang,
- Chengang Xiang,
- Chengang Xiang,
- Li Yang,
- Li Yang,
- Li Yang,
- Li Yang,
- Li Yang
Affiliations
- Xin Kang
- Renal Division, Renal Pathology Center, Peking University First Hospital, Beijing, China
- Xin Kang
- Institute of Nephrology, Peking University, Beijing, China
- Xin Kang
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Ying Chen
- Renal Division, Renal Pathology Center, Peking University First Hospital, Beijing, China
- Ying Chen
- Institute of Nephrology, Peking University, Beijing, China
- Ying Chen
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Ying Chen
- Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Peking University, Beijing, China
- Ying Chen
- Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
- Xiaohong Xin
- Renal Division, Renal Pathology Center, Peking University First Hospital, Beijing, China
- Xiaohong Xin
- Institute of Nephrology, Peking University, Beijing, China
- Xiaohong Xin
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Menghan Liu
- Renal Division, Renal Pathology Center, Peking University First Hospital, Beijing, China
- Menghan Liu
- Institute of Nephrology, Peking University, Beijing, China
- Menghan Liu
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Yuan Ma
- Renal Division, Renal Pathology Center, Peking University First Hospital, Beijing, China
- Yuan Ma
- Institute of Nephrology, Peking University, Beijing, China
- Yuan Ma
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Yifei Ren
- Renal Division, Renal Pathology Center, Peking University First Hospital, Beijing, China
- Yifei Ren
- Institute of Nephrology, Peking University, Beijing, China
- Yifei Ren
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Jing Ji
- Renal Division, Renal Pathology Center, Peking University First Hospital, Beijing, China
- Jing Ji
- Institute of Nephrology, Peking University, Beijing, China
- Jing Ji
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Qi Yu
- Renal Division, Renal Pathology Center, Peking University First Hospital, Beijing, China
- Qi Yu
- Institute of Nephrology, Peking University, Beijing, China
- Qi Yu
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Lei Qu
- Renal Division, Renal Pathology Center, Peking University First Hospital, Beijing, China
- Lei Qu
- Institute of Nephrology, Peking University, Beijing, China
- Lei Qu
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Suxia Wang
- Laboratory of Electron Microscopy, Pathological Center, Peking University First Hospital, Beijing, China
- Gang Liu
- Renal Division, Renal Pathology Center, Peking University First Hospital, Beijing, China
- Gang Liu
- Institute of Nephrology, Peking University, Beijing, China
- Gang Liu
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Gang Liu
- Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Peking University, Beijing, China
- Gang Liu
- Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
- Chengang Xiang
- Renal Division, Renal Pathology Center, Peking University First Hospital, Beijing, China
- Chengang Xiang
- Institute of Nephrology, Peking University, Beijing, China
- Chengang Xiang
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Chengang Xiang
- Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Peking University, Beijing, China
- Chengang Xiang
- Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
- Li Yang
- Renal Division, Renal Pathology Center, Peking University First Hospital, Beijing, China
- Li Yang
- Institute of Nephrology, Peking University, Beijing, China
- Li Yang
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Li Yang
- Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Peking University, Beijing, China
- Li Yang
- Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
- DOI
- https://doi.org/10.3389/fcell.2021.752053
- Journal volume & issue
-
Vol. 9
Abstract
Background: Cisplatin is a widely used chemotherapeutic drug, whereas the clinical application is greatly limited by its nephrotoxic side effect. Currently, there has been no effective treatment to prevent cisplatin-induced acute kidney injury (cisplatin-AKI). Human amniotic epithelial cells (hAECs) and their derived exosomes (EXOs) have been proven to effectively protect against ischemia reperfusion-induced AKI, yet their roles in cisplatin-AKI are still unknown.Methods: C57BL/6J mice were given two doses of cisplatin at 20 or 15 mg/kg of body weight to induce AKI with or without mortality. hAECs or EXOs were injected via tail vein 1 day after cisplatin administration. Serum and kidney tissues were collected on the fourth day after 15 mg/kg cisplatin treatment to explore the nephro-protective effects of hAECs and EXOs on cisplatin-AKI. Lung cancer xenograft model was built by subcutaneous injection of A549 cells into BALB/c nude mice to evaluate the effect of hAECs or EXOs on cisplatin chemotherapy.Results: Cisplatin nephrotoxicity was significantly attenuated by hAECs and EXOs as evidenced by reduced mortality rate and decreased serum creatinine (sCr) and reduced tubular injury score. hAECs or EXOs exerted the nephro-protective effects via suppression of TNF-α/MAPK and caspase signaling pathways. In the A549 lung cancer xenograft mouse model, administration of hAECs or EXOs did not promote tumor growth or compromise the therapeutic effects of cisplatin on tumors.Conclusion: This study is the first to demonstrate that hAECs and their derived exosomes have nephro-protective effects in cisplatin-AKI in vivo. Importantly, neither hAECs nor EXOs compromise the antitumor activity of cisplatin. These results potentially support the use of hAECs and their derived EXOs as nephro-protectors against cisplatin-induced nephrotoxicity clinically.
Keywords
