Hypoxic preconditioning with cobalt of bone marrow mesenchymal stem cells improves cell migration and enhances therapy for treatment of ischemic acute kidney injury.

Mesenchymal stem cell (MSC) administration is known to enhance the recovery of the kidney following injury. Here we tested the potential of hypoxic-preconditioned-MSC transplantation to enhance the efficacy of cell therapy on acute kidney injury (AKI) by improving MSC migration to the injured kidney...

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Autores principales:	Xiaofang Yu, Chunlai Lu, Hong Liu, Shengxiang Rao, Jieru Cai, Shaopeng Liu, Alison J Kriegel, Andrew S Greene, Minyu Liang, Xiaoqiang Ding
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a41784bc3ee34802b912141270d2d21b
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spelling	oai:doaj.org-article:a41784bc3ee34802b912141270d2d21b2021-11-18T07:46:14ZHypoxic preconditioning with cobalt of bone marrow mesenchymal stem cells improves cell migration and enhances therapy for treatment of ischemic acute kidney injury.1932-620310.1371/journal.pone.0062703https://doaj.org/article/a41784bc3ee34802b912141270d2d21b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23671625/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Mesenchymal stem cell (MSC) administration is known to enhance the recovery of the kidney following injury. Here we tested the potential of hypoxic-preconditioned-MSC transplantation to enhance the efficacy of cell therapy on acute kidney injury (AKI) by improving MSC migration to the injured kidney. Cobalt was used as hypoxia mimetic preconditioning (HMP). MSC were subjected to HMP through 24 h culture in 200 µmol/L cobalt. Compared to normoxia cultured MSC (NP-MSC), HMP significantly increased the expression of HIF-1α and CXCR4 in MSC and enhanced the migration of MSC in vitro. This effect was lost when MSC were treated with siRNA targeting HIF-1α or CXCR4 antagonist. SPIO labeled MSC were administered to rats with I/R injury followed immediately by magnetic resonance imaging. Imaging clearly showed that HMP-MSC exhibited greater migration and a longer retention time in the ischemic kidney than NP-MSC. Histological evaluation showed more HMP-MSC in the glomerular capillaries of ischemic kidneys than in the kidneys receiving NP-MSC. Occasional tubules showed iron labeling in the HMP group, while no tubules had iron labeling in NP group, indicating the possibility of tubular transdifferentiation after HMP. These results were also confirmed by fluorescence microscopy study using CM-DiI labeling. The increased recruitment of HMP-MSC was associated with reduced kidney injury and enhanced functional recovery. This effect was also related to the increased paracrine action by HMP-MSC. Thus we suggest that by enhancing MSC migration and prolonging kidney retention, hypoxic preconditioning of MSC may be a useful approach for developing AKI cell therapy.Xiaofang YuChunlai LuHong LiuShengxiang RaoJieru CaiShaopeng LiuAlison J KriegelAndrew S GreeneMinyu LiangXiaoqiang DingPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e62703 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaofang Yu Chunlai Lu Hong Liu Shengxiang Rao Jieru Cai Shaopeng Liu Alison J Kriegel Andrew S Greene Minyu Liang Xiaoqiang Ding Hypoxic preconditioning with cobalt of bone marrow mesenchymal stem cells improves cell migration and enhances therapy for treatment of ischemic acute kidney injury.
description	Mesenchymal stem cell (MSC) administration is known to enhance the recovery of the kidney following injury. Here we tested the potential of hypoxic-preconditioned-MSC transplantation to enhance the efficacy of cell therapy on acute kidney injury (AKI) by improving MSC migration to the injured kidney. Cobalt was used as hypoxia mimetic preconditioning (HMP). MSC were subjected to HMP through 24 h culture in 200 µmol/L cobalt. Compared to normoxia cultured MSC (NP-MSC), HMP significantly increased the expression of HIF-1α and CXCR4 in MSC and enhanced the migration of MSC in vitro. This effect was lost when MSC were treated with siRNA targeting HIF-1α or CXCR4 antagonist. SPIO labeled MSC were administered to rats with I/R injury followed immediately by magnetic resonance imaging. Imaging clearly showed that HMP-MSC exhibited greater migration and a longer retention time in the ischemic kidney than NP-MSC. Histological evaluation showed more HMP-MSC in the glomerular capillaries of ischemic kidneys than in the kidneys receiving NP-MSC. Occasional tubules showed iron labeling in the HMP group, while no tubules had iron labeling in NP group, indicating the possibility of tubular transdifferentiation after HMP. These results were also confirmed by fluorescence microscopy study using CM-DiI labeling. The increased recruitment of HMP-MSC was associated with reduced kidney injury and enhanced functional recovery. This effect was also related to the increased paracrine action by HMP-MSC. Thus we suggest that by enhancing MSC migration and prolonging kidney retention, hypoxic preconditioning of MSC may be a useful approach for developing AKI cell therapy.
format	article
author	Xiaofang Yu Chunlai Lu Hong Liu Shengxiang Rao Jieru Cai Shaopeng Liu Alison J Kriegel Andrew S Greene Minyu Liang Xiaoqiang Ding
author_facet	Xiaofang Yu Chunlai Lu Hong Liu Shengxiang Rao Jieru Cai Shaopeng Liu Alison J Kriegel Andrew S Greene Minyu Liang Xiaoqiang Ding
author_sort	Xiaofang Yu
title	Hypoxic preconditioning with cobalt of bone marrow mesenchymal stem cells improves cell migration and enhances therapy for treatment of ischemic acute kidney injury.
title_short	Hypoxic preconditioning with cobalt of bone marrow mesenchymal stem cells improves cell migration and enhances therapy for treatment of ischemic acute kidney injury.
title_full	Hypoxic preconditioning with cobalt of bone marrow mesenchymal stem cells improves cell migration and enhances therapy for treatment of ischemic acute kidney injury.
title_fullStr	Hypoxic preconditioning with cobalt of bone marrow mesenchymal stem cells improves cell migration and enhances therapy for treatment of ischemic acute kidney injury.
title_full_unstemmed	Hypoxic preconditioning with cobalt of bone marrow mesenchymal stem cells improves cell migration and enhances therapy for treatment of ischemic acute kidney injury.
title_sort	hypoxic preconditioning with cobalt of bone marrow mesenchymal stem cells improves cell migration and enhances therapy for treatment of ischemic acute kidney injury.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/a41784bc3ee34802b912141270d2d21b
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_version_	1718422992248111104

Hypoxic preconditioning with cobalt of bone marrow mesenchymal stem cells improves cell migration and enhances therapy for treatment of ischemic acute kidney injury.

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