Hypoxia-Pretreated Human MSCs Attenuate Acute Kidney Injury through Enhanced Angiogenic and Antioxidative Capacities

Hypoxia preconditioning has been confirmed as an effective strategy to enhance the therapeutic potentials of mesenchymal stem cells (MSCs), such as for myocardial ischemia. However, whether hypoxia preconditioning would produce beneficial effects on MSC-based renal repair has not been demonstrated....

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Main Authors: Wenbo Zhang, Lirui Liu, Yanhong Huo, Yonghong Yang, Yaping Wang
Format: Article
Language:English
Published: Hindawi Limited 2014-01-01
Series:BioMed Research International
Online Access:http://dx.doi.org/10.1155/2014/462472
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spelling doaj-ce60a40c640d4360bbeb7deafba390002020-11-24T23:07:08ZengHindawi LimitedBioMed Research International2314-61332314-61412014-01-01201410.1155/2014/462472462472Hypoxia-Pretreated Human MSCs Attenuate Acute Kidney Injury through Enhanced Angiogenic and Antioxidative CapacitiesWenbo Zhang0Lirui Liu1Yanhong Huo2Yonghong Yang3Yaping Wang4Department of Nephrology, The General Hospital of Beijing Military District, South Mencang 5, Dongcheng District, Beijing 100700, ChinaDepartment of Nephrology, The General Hospital of Beijing Military District, South Mencang 5, Dongcheng District, Beijing 100700, ChinaDepartment of Nephrology, The General Hospital of Beijing Military District, South Mencang 5, Dongcheng District, Beijing 100700, ChinaDepartment of Nephrology, The General Hospital of Beijing Military District, South Mencang 5, Dongcheng District, Beijing 100700, ChinaDepartment of Nephrology, The General Hospital of Beijing Military District, South Mencang 5, Dongcheng District, Beijing 100700, ChinaHypoxia preconditioning has been confirmed as an effective strategy to enhance the therapeutic potentials of mesenchymal stem cells (MSCs), such as for myocardial ischemia. However, whether hypoxia preconditioning would produce beneficial effects on MSC-based renal repair has not been demonstrated. In the study, we aimed to determine the feasibility and efficacy of hypoxia preconditioning to enhance MSC-based therapy of acute kidney injury (AKI). MSCs were isolated from human adipose tissues. The paracrine effects of MSCs under normoxia and hypoxia were determined in vitro. Rats of AKI were induced by kidney I/R surgery and randomly divided into three groups: I/R control receiving PBS injection; MSC group receiving normal MSC injection; hypoMSC group receiving hypoxia-preconditioned MSC injection. It was demonstrated in vitro that paracrine effects of MSCs were significantly enhanced, especially angiogenic factors. Dihydroethidium (DHE) staining showed that antioxidative activities of MSCs were significantly enhanced by hypoxia stimulation. Vascularization, apoptosis, and histological injury were all significantly improved in hypoMSC injected group compared with that in control and MSC injected groups. Finally, the renal function was also significantly improved in hypoMSC injected group compared with that in the other two groups as assessed by the serum creatinine and BUN levels.http://dx.doi.org/10.1155/2014/462472
collection DOAJ
language English
format Article
sources DOAJ
author Wenbo Zhang
Lirui Liu
Yanhong Huo
Yonghong Yang
Yaping Wang
spellingShingle Wenbo Zhang
Lirui Liu
Yanhong Huo
Yonghong Yang
Yaping Wang
Hypoxia-Pretreated Human MSCs Attenuate Acute Kidney Injury through Enhanced Angiogenic and Antioxidative Capacities
BioMed Research International
author_facet Wenbo Zhang
Lirui Liu
Yanhong Huo
Yonghong Yang
Yaping Wang
author_sort Wenbo Zhang
title Hypoxia-Pretreated Human MSCs Attenuate Acute Kidney Injury through Enhanced Angiogenic and Antioxidative Capacities
title_short Hypoxia-Pretreated Human MSCs Attenuate Acute Kidney Injury through Enhanced Angiogenic and Antioxidative Capacities
title_full Hypoxia-Pretreated Human MSCs Attenuate Acute Kidney Injury through Enhanced Angiogenic and Antioxidative Capacities
title_fullStr Hypoxia-Pretreated Human MSCs Attenuate Acute Kidney Injury through Enhanced Angiogenic and Antioxidative Capacities
title_full_unstemmed Hypoxia-Pretreated Human MSCs Attenuate Acute Kidney Injury through Enhanced Angiogenic and Antioxidative Capacities
title_sort hypoxia-pretreated human mscs attenuate acute kidney injury through enhanced angiogenic and antioxidative capacities
publisher Hindawi Limited
series BioMed Research International
issn 2314-6133
2314-6141
publishDate 2014-01-01
description Hypoxia preconditioning has been confirmed as an effective strategy to enhance the therapeutic potentials of mesenchymal stem cells (MSCs), such as for myocardial ischemia. However, whether hypoxia preconditioning would produce beneficial effects on MSC-based renal repair has not been demonstrated. In the study, we aimed to determine the feasibility and efficacy of hypoxia preconditioning to enhance MSC-based therapy of acute kidney injury (AKI). MSCs were isolated from human adipose tissues. The paracrine effects of MSCs under normoxia and hypoxia were determined in vitro. Rats of AKI were induced by kidney I/R surgery and randomly divided into three groups: I/R control receiving PBS injection; MSC group receiving normal MSC injection; hypoMSC group receiving hypoxia-preconditioned MSC injection. It was demonstrated in vitro that paracrine effects of MSCs were significantly enhanced, especially angiogenic factors. Dihydroethidium (DHE) staining showed that antioxidative activities of MSCs were significantly enhanced by hypoxia stimulation. Vascularization, apoptosis, and histological injury were all significantly improved in hypoMSC injected group compared with that in control and MSC injected groups. Finally, the renal function was also significantly improved in hypoMSC injected group compared with that in the other two groups as assessed by the serum creatinine and BUN levels.
url http://dx.doi.org/10.1155/2014/462472
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