Journal article
Human Mesenchymal Stem Cell Therapy Reverses Su5416/Hypoxia-Induced Pulmonary Arterial Hypertension in Mice
Frontiers in pharmacology, Vol.9, p.1395
12/06/2018
DOI: 10.3389/fphar.2018.01395
PMCID: PMC6291748
PMID: 30574088
Abstract
Aims: Pulmonary arterial hypertension (PAH) is a disease characterized by an increase in pulmonary vascular resistance and right ventricular (RV) failure. We aimed to determine the effects of human mesenchymal stem cell (hMSC) therapy in a SU5416/hypoxia (SuH) mice model of PAH. Methods and Results: C57BL/6 mice (20–25 g) were exposure to 4 weeks of hypoxia combined vascular endothelial growth factor receptor antagonism (20 mg/kg SU5416; weekly s.c. injections; PAH mice). Control mice were housed in room air. Following 2 weeks of SuH exposure, we injected 5 × 105 hMSCs cells suspended in 50 μL of vehicle (0.6 U/mL DNaseI in PBS) through intravenous injection in the caudal vein. PAH mice were treated only with vehicle. Ratio between pulmonary artery acceleration time and RV ejection time (PAAT/RVET), measure by echocardiography, was significantly reduced in the PAH mice, compared with controls, and therapy with hMSCs normalized this. Significant muscularization of the PA was observed in the PAH mice and hMSC reduced the number of fully muscularized vessels. RV free wall thickness was higher in PAH animals than in the controls, and a single injection of hMSCs reversed RV hypertrophy. Levels of markers of exacerbated apoptosis, tissue inflammation and damage, cell proliferation and oxidative stress were significantly greater in both lungs and RV tissues from PAH group, compared to controls. hMSC injection in PAH animals normalized the expression of these molecules which are involved with PAH and RV dysfunction development and the state of chronicity. Conclusion: These results indicate that hMSCs therapy represents a novel strategy for the treatment of PAH in the future.
Details
- Title: Subtitle
- Human Mesenchymal Stem Cell Therapy Reverses Su5416/Hypoxia-Induced Pulmonary Arterial Hypertension in Mice
- Creators
- Allan K. N. Alencar - , , , , , , , , , , , ,Pedro M. Pimentel-Coelho - Universidade Federal do Rio de JaneiroGuilherme C. Montes - Universidade Federal do Rio de JaneiroMarina de M. C. da Silva - , , , , , , , , , , , ,Luiza V. P. Mendes - Universidade Federal do Rio de JaneiroTadeu L. Montagnoli - Universidade Federal do Rio de JaneiroAnanssa M. S. Silva - Universidade Federal do Rio de JaneiroJuliana Ferreira Vasques - Universidade Federal do Rio de JaneiroPaulo Henrique Rosado-de-Castro - Universidade Federal do Rio de JaneiroBianca Gutfilen - Universidade Federal do Rio de JaneiroValéria do M. N. Cunha - Universidade Federal do Rio de JaneiroAline G. M. Fraga - Universidade Federal do Rio de JaneiroPatrícia M R e Silva - , , , , , , , , , , , ,Marco Aurélio Martins - Fundação Oswaldo CruzTatiana Paula Teixeira Ferreira - Fundação Oswaldo CruzRosalia Mendes-Otero - Universidade Federal do Rio de JaneiroMargarete M. Trachez - Universidade Federal do Rio de JaneiroRoberto T. Sudo - Universidade Federal do Rio de JaneiroGisele Zapata-Sudo - Universidade Federal do Rio de Janeiro
- Resource Type
- Journal article
- Publication Details
- Frontiers in pharmacology, Vol.9, p.1395
- DOI
- 10.3389/fphar.2018.01395
- PMID
- 30574088
- PMCID
- PMC6291748
- NLM abbreviation
- Front Pharmacol
- ISSN
- 1663-9812
- eISSN
- 1663-9812
- Publisher
- Frontiers Media S.A
- Language
- English
- Date published
- 12/06/2018
- Academic Unit
- Radiology
- Record Identifier
- 9985143551902771
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