Therapeutic benefit of mesenchymal stem cells in pregnant rats with angiotensin receptor agonistic autoantibody-induced hypertension: Implications for immunomodulation and cytoprotection

Immunomodulation by mesenchymal stem cells (MSCs) is potentially important for maintaining peripheral tolerance. Preeclampsia may be due to maternal immune rejection of the genetically foreign fetus. This study aimed to investigate the biological function of human umbilical cord–derived mesenchymal...

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Main Authors: Dan Zhang, Lihua Fu, Leilei Wang, Lin Lin, Lihong Yu, Lijun Zhang, Tao Shang
Format: Article
Language:English
Published: Taylor & Francis Group 2017-07-01
Series:Hypertension in Pregnancy
Subjects:
Online Access:http://dx.doi.org/10.1080/10641955.2017.1329429
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author Dan Zhang
Lihua Fu
Leilei Wang
Lin Lin
Lihong Yu
Lijun Zhang
Tao Shang
author_facet Dan Zhang
Lihua Fu
Leilei Wang
Lin Lin
Lihong Yu
Lijun Zhang
Tao Shang
author_sort Dan Zhang
collection DOAJ
description Immunomodulation by mesenchymal stem cells (MSCs) is potentially important for maintaining peripheral tolerance. Preeclampsia may be due to maternal immune rejection of the genetically foreign fetus. This study aimed to investigate the biological function of human umbilical cord–derived mesenchymal stem cells (HU-MSCs) for the treatment of angiotensin receptor agonistic autoantibody (AT1-AA)-induced hypertension during pregnancy. HU-MSCs were isolated, cultured, and labeled in vitro. AT1-AA and HU-MSCs were administered to pregnant rats. Green fluorescent protein (GFP)–positive HU-MSCs infused in vivo were identified by immunofluorescence. Systolic blood pressure (SBP) was evaluated. The effects of HU-MSCs on fetal weight, kidney burden, and spiral artery remodeling, as well as on the expression of tumor necrosis factor α (TNF-α), interleukin 10 (IL-10), and heme oxygenase 1 (HO-1), were investigated. The SBP levels in the HU-MSC-treated pregnant hypertension rats decreased by gestational day 19. The reduction in fetal weight was largely ameliorated after HU-MSC treatment. Lesion burden in the kidney was attenuated and spiral artery remodeling was improved in HU-MSC-treated pregnant hypertension rats. However, green fluorescent protein (GFP)–labeled cells were sparingly observed in the kidney and placenta. Intravenous infusion of HU-MSCs into AT1-AA-induced rats significantly downregulated serum TNF-α levels and upregulated IL-10 levels, concomitant with increased placenta and mesometrial triangle (MT) HO-1 expression. Taken together, intravenous infusion of HU-MSCs ameliorates AT1-AA-induced pregnancy hypertension, intrauterine growth retardation, kidney impairment, and spiral artery remodeling impairment. Moreover, the potential benefits of HU-MSCs may be attributable to both an interference with the pathogenic immune response and a paracrine cytoprotective action.
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spelling doaj.art-51870f9e12c64526b2e192e011d81b4a2023-09-19T09:24:42ZengTaylor & Francis GroupHypertension in Pregnancy1064-19551525-60652017-07-0136324725810.1080/10641955.2017.13294291329429Therapeutic benefit of mesenchymal stem cells in pregnant rats with angiotensin receptor agonistic autoantibody-induced hypertension: Implications for immunomodulation and cytoprotectionDan Zhang0Lihua Fu1Leilei Wang2Lin Lin3Lihong Yu4Lijun Zhang5Tao Shang6Shenyang Women’s and Children’s HospitalDitan Hospital Capital Medical UniversityShengjing Hospital of China Medical UniversityShenyang Women’s and Children’s HospitalShenyang Women’s and Children’s HospitalShenyang Women’s and Children’s HospitalShengjing Hospital of China Medical UniversityImmunomodulation by mesenchymal stem cells (MSCs) is potentially important for maintaining peripheral tolerance. Preeclampsia may be due to maternal immune rejection of the genetically foreign fetus. This study aimed to investigate the biological function of human umbilical cord–derived mesenchymal stem cells (HU-MSCs) for the treatment of angiotensin receptor agonistic autoantibody (AT1-AA)-induced hypertension during pregnancy. HU-MSCs were isolated, cultured, and labeled in vitro. AT1-AA and HU-MSCs were administered to pregnant rats. Green fluorescent protein (GFP)–positive HU-MSCs infused in vivo were identified by immunofluorescence. Systolic blood pressure (SBP) was evaluated. The effects of HU-MSCs on fetal weight, kidney burden, and spiral artery remodeling, as well as on the expression of tumor necrosis factor α (TNF-α), interleukin 10 (IL-10), and heme oxygenase 1 (HO-1), were investigated. The SBP levels in the HU-MSC-treated pregnant hypertension rats decreased by gestational day 19. The reduction in fetal weight was largely ameliorated after HU-MSC treatment. Lesion burden in the kidney was attenuated and spiral artery remodeling was improved in HU-MSC-treated pregnant hypertension rats. However, green fluorescent protein (GFP)–labeled cells were sparingly observed in the kidney and placenta. Intravenous infusion of HU-MSCs into AT1-AA-induced rats significantly downregulated serum TNF-α levels and upregulated IL-10 levels, concomitant with increased placenta and mesometrial triangle (MT) HO-1 expression. Taken together, intravenous infusion of HU-MSCs ameliorates AT1-AA-induced pregnancy hypertension, intrauterine growth retardation, kidney impairment, and spiral artery remodeling impairment. Moreover, the potential benefits of HU-MSCs may be attributable to both an interference with the pathogenic immune response and a paracrine cytoprotective action.http://dx.doi.org/10.1080/10641955.2017.1329429angiotensin receptor agonistic autoantibodymesenchymal stem cellspreeclampsiaspiral artery remodeling
spellingShingle Dan Zhang
Lihua Fu
Leilei Wang
Lin Lin
Lihong Yu
Lijun Zhang
Tao Shang
Therapeutic benefit of mesenchymal stem cells in pregnant rats with angiotensin receptor agonistic autoantibody-induced hypertension: Implications for immunomodulation and cytoprotection
Hypertension in Pregnancy
angiotensin receptor agonistic autoantibody
mesenchymal stem cells
preeclampsia
spiral artery remodeling
title Therapeutic benefit of mesenchymal stem cells in pregnant rats with angiotensin receptor agonistic autoantibody-induced hypertension: Implications for immunomodulation and cytoprotection
title_full Therapeutic benefit of mesenchymal stem cells in pregnant rats with angiotensin receptor agonistic autoantibody-induced hypertension: Implications for immunomodulation and cytoprotection
title_fullStr Therapeutic benefit of mesenchymal stem cells in pregnant rats with angiotensin receptor agonistic autoantibody-induced hypertension: Implications for immunomodulation and cytoprotection
title_full_unstemmed Therapeutic benefit of mesenchymal stem cells in pregnant rats with angiotensin receptor agonistic autoantibody-induced hypertension: Implications for immunomodulation and cytoprotection
title_short Therapeutic benefit of mesenchymal stem cells in pregnant rats with angiotensin receptor agonistic autoantibody-induced hypertension: Implications for immunomodulation and cytoprotection
title_sort therapeutic benefit of mesenchymal stem cells in pregnant rats with angiotensin receptor agonistic autoantibody induced hypertension implications for immunomodulation and cytoprotection
topic angiotensin receptor agonistic autoantibody
mesenchymal stem cells
preeclampsia
spiral artery remodeling
url http://dx.doi.org/10.1080/10641955.2017.1329429
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