Human amniotic epithelial cells ameliorate kidney damage in ischemia-reperfusion mouse model of acute kidney injury
Abstract Background Acute kidney injury (AKI) is a common clinical disease with complex pathophysiology and limited therapeutic choices. This prompts the need for novel therapy targeting multiple aspects of this disease. Human amnion epithelial cell (hAEC) is an ideal stem cell source. Increasing ev...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-09-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-020-01917-y |
| _version_ | 1828399881658564608 |
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| author | Yifei Ren Ying Chen Xizi Zheng Hui Wang Xin Kang Jiawei Tang Lei Qu Xiaoyan Shao Suxia Wang Shuangling Li Gang Liu Li Yang |
| author_facet | Yifei Ren Ying Chen Xizi Zheng Hui Wang Xin Kang Jiawei Tang Lei Qu Xiaoyan Shao Suxia Wang Shuangling Li Gang Liu Li Yang |
| author_sort | Yifei Ren |
| collection | DOAJ |
| description | Abstract Background Acute kidney injury (AKI) is a common clinical disease with complex pathophysiology and limited therapeutic choices. This prompts the need for novel therapy targeting multiple aspects of this disease. Human amnion epithelial cell (hAEC) is an ideal stem cell source. Increasing evidence suggests that exosomes may act as critical cell–cell communicators. Accordingly, we assessed the therapeutic potential of hAECs and their derived exosomes (hAECs-EXO) in ischemia reperfusion mouse model of AKI and explored the underlying mechanisms. Methods The hAECs were primary cultured, and hAECs-EXO were isolated and characterized. An ischemic-reperfusion injury-induced AKI (IRI-AKI) mouse model was established to mimic clinical ischemic kidney injury with different disease severity. Mouse blood creatinine level was used to assess renal function, and kidney specimens were processed to detect cell proliferation, apoptosis, and capillary density. Macrophage infiltration was analyzed by flow cytometry. hAEC-derived exosomes (hAECs-EXO) were used to treat hypoxia-reoxygenation (H/R) injured HK-2 cells and mouse bone marrow-derived macrophages to evaluate their protective effect in vitro. Furthermore, hAECs-EXO were subjected to liquid chromatography-tandem mass spectrometry for proteomic profiling. Results We found that systematically administered hAECs could improve mortality and renal function in IRI-AKI mice, decrease the number of apoptotic cells, prevent peritubular capillary loss, and modulate kidney local immune response. However, hAECs showed very low kidney tissue integration. Exosomes isolated from hAECs recapitulated the renal protective effects of their source cells. In vitro, hAECs-EXO protected HK-2 cells from H/R injury-induced apoptosis and promoted bone marrow-derived macrophage polarization toward M2 phenotype. Proteomic analysis on hAECs-EXO revealed proteins involved in extracellular matrix organization, growth factor signaling pathways, cytokine production, and immunomodulation. These findings demonstrated that paracrine of exosomes might be the key mechanism of hAECs in alleviating renal ischemia reperfusion injury. Conclusions We reported hAECs could improve survival and ameliorate renal injury in mice with IRI-AKI. The anti-apoptotic, pro-angiogenetic, and immunomodulatory capabilities of hAECs are at least partially, through paracrine pathways. hAECs-EXO might be a promising clinical therapeutic tool, overcoming the weaknesses and risks associated with the use of native stem cells, for patients with AKI. |
| first_indexed | 2024-12-10T09:23:42Z |
| format | Article |
| id | doaj.art-50807747724f43158703537f0f1507df |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-10T09:23:42Z |
| publishDate | 2020-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-50807747724f43158703537f0f1507df2022-12-22T01:54:36ZengBMCStem Cell Research & Therapy1757-65122020-09-0111111610.1186/s13287-020-01917-yHuman amniotic epithelial cells ameliorate kidney damage in ischemia-reperfusion mouse model of acute kidney injuryYifei Ren0Ying Chen1Xizi Zheng2Hui Wang3Xin Kang4Jiawei Tang5Lei Qu6Xiaoyan Shao7Suxia Wang8Shuangling Li9Gang Liu10Li Yang11Renal Division, Peking University First Hospital, Peking University Institute of NephrologyRenal Division, Peking University First Hospital, Peking University Institute of NephrologyRenal Division, Peking University First Hospital, Peking University Institute of NephrologyRenal Division, Peking University First Hospital, Peking University Institute of NephrologyRenal Division, Peking University First Hospital, Peking University Institute of NephrologyRenal Division, Peking University First Hospital, Peking University Institute of NephrologyRenal Division, Peking University First Hospital, Peking University Institute of NephrologyShanghai iCELL Biotechnology Co Ltd.Renal Division, Peking University First Hospital, Peking University Institute of NephrologyDepartment of Critical Care Medicine, Peking University First HospitalRenal Division, Peking University First Hospital, Peking University Institute of NephrologyRenal Division, Peking University First Hospital, Peking University Institute of NephrologyAbstract Background Acute kidney injury (AKI) is a common clinical disease with complex pathophysiology and limited therapeutic choices. This prompts the need for novel therapy targeting multiple aspects of this disease. Human amnion epithelial cell (hAEC) is an ideal stem cell source. Increasing evidence suggests that exosomes may act as critical cell–cell communicators. Accordingly, we assessed the therapeutic potential of hAECs and their derived exosomes (hAECs-EXO) in ischemia reperfusion mouse model of AKI and explored the underlying mechanisms. Methods The hAECs were primary cultured, and hAECs-EXO were isolated and characterized. An ischemic-reperfusion injury-induced AKI (IRI-AKI) mouse model was established to mimic clinical ischemic kidney injury with different disease severity. Mouse blood creatinine level was used to assess renal function, and kidney specimens were processed to detect cell proliferation, apoptosis, and capillary density. Macrophage infiltration was analyzed by flow cytometry. hAEC-derived exosomes (hAECs-EXO) were used to treat hypoxia-reoxygenation (H/R) injured HK-2 cells and mouse bone marrow-derived macrophages to evaluate their protective effect in vitro. Furthermore, hAECs-EXO were subjected to liquid chromatography-tandem mass spectrometry for proteomic profiling. Results We found that systematically administered hAECs could improve mortality and renal function in IRI-AKI mice, decrease the number of apoptotic cells, prevent peritubular capillary loss, and modulate kidney local immune response. However, hAECs showed very low kidney tissue integration. Exosomes isolated from hAECs recapitulated the renal protective effects of their source cells. In vitro, hAECs-EXO protected HK-2 cells from H/R injury-induced apoptosis and promoted bone marrow-derived macrophage polarization toward M2 phenotype. Proteomic analysis on hAECs-EXO revealed proteins involved in extracellular matrix organization, growth factor signaling pathways, cytokine production, and immunomodulation. These findings demonstrated that paracrine of exosomes might be the key mechanism of hAECs in alleviating renal ischemia reperfusion injury. Conclusions We reported hAECs could improve survival and ameliorate renal injury in mice with IRI-AKI. The anti-apoptotic, pro-angiogenetic, and immunomodulatory capabilities of hAECs are at least partially, through paracrine pathways. hAECs-EXO might be a promising clinical therapeutic tool, overcoming the weaknesses and risks associated with the use of native stem cells, for patients with AKI.http://link.springer.com/article/10.1186/s13287-020-01917-yAcute kidney injuryHuman amnion epithelial cellsExosomeCell therapyIschemia |
| spellingShingle | Yifei Ren Ying Chen Xizi Zheng Hui Wang Xin Kang Jiawei Tang Lei Qu Xiaoyan Shao Suxia Wang Shuangling Li Gang Liu Li Yang Human amniotic epithelial cells ameliorate kidney damage in ischemia-reperfusion mouse model of acute kidney injury Stem Cell Research & Therapy Acute kidney injury Human amnion epithelial cells Exosome Cell therapy Ischemia |
| title | Human amniotic epithelial cells ameliorate kidney damage in ischemia-reperfusion mouse model of acute kidney injury |
| title_full | Human amniotic epithelial cells ameliorate kidney damage in ischemia-reperfusion mouse model of acute kidney injury |
| title_fullStr | Human amniotic epithelial cells ameliorate kidney damage in ischemia-reperfusion mouse model of acute kidney injury |
| title_full_unstemmed | Human amniotic epithelial cells ameliorate kidney damage in ischemia-reperfusion mouse model of acute kidney injury |
| title_short | Human amniotic epithelial cells ameliorate kidney damage in ischemia-reperfusion mouse model of acute kidney injury |
| title_sort | human amniotic epithelial cells ameliorate kidney damage in ischemia reperfusion mouse model of acute kidney injury |
| topic | Acute kidney injury Human amnion epithelial cells Exosome Cell therapy Ischemia |
| url | http://link.springer.com/article/10.1186/s13287-020-01917-y |
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