Human Mesenchymal Stem Cell Therapy Reverses Su5416/Hypoxia-Induced Pulmonary Arterial Hypertension in Mice
| Autor: | Luiza V.P. Mendes, Pedro M. Pimentel-Coelho, Margarete M. Trachez, Patrícia M.R. e Silva, Tatiana P. T. Ferreira, Paulo Henrique Rosado-de-Castro, Roberto T. Sudo, Allan K Alencar, Ananssa M Silva, Aline Guerra Manssour Fraga, Marina M. Silva, Bianca Gutfilen, Marco A. Martins, Guilherme C Montes, Gisele Zapata-Sudo, Tadeu L Montagnoli, Valéria M.N. Cunha, Juliana Ferreira Vasques, Rosalia Mendes-Otero |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Inflammation 030204 cardiovascular system & hematology medicine.disease_cause 03 medical and health sciences 0302 clinical medicine human mesenchymal stem cell pulmonary arterial hypertension medicine.artery Internal medicine Medicine Pharmacology (medical) Original Research Pharmacology business.industry Cell growth lcsh:RM1-950 Mesenchymal stem cell apoptosis Hypoxia (medical) cell proliferation lcsh:Therapeutics. Pharmacology 030104 developmental biology medicine.anatomical_structure Endocrinology inflammation Apoptosis Pulmonary artery Vascular resistance medicine.symptom business Oxidative stress |
| Zdroj: | Frontiers in Pharmacology, Vol 9 (2018) Frontiers in Pharmacology |
| ISSN: | 1663-9812 |
| DOI: | 10.3389/fphar.2018.01395 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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