Journal
CIRCULATION JOURNAL
Volume 76, Issue 4, Pages 977-985Publisher
JAPANESE CIRCULATION SOC
DOI: 10.1253/circj.CJ-11-1175
Keywords
ABM-MNCs; DMCT; Pulmonary hypertension
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Funding
- Independent Innovation Foundation of Shandong University, IIFSDU [2010TS051]
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Background: We investigated the safety and feasibility of intratracheal administration of autologous bone marrow-derived mononuclear cells (ABM-MNCs) and observed the effects in a canine model of pulmonary hypertension (PH). Methods and Results: The PH model was induced by intravenous injection of 3 mg/kg dehydromonocrotaline (DMCT) via the right atrium. Two weeks after DMCT administration, the animals received 4 different treatments (n=10 in each group): (I) negative control group; (II): ABM-MNCs group; (Ill) PH group; (IV) PH+ABM-MNCs group. Six weeks after injection of cells (10(7)), the hemodynamic data were significantly improved in group IV compared with group III (P<0.05). The ratio of right ventricular weight to left ventricular plus septal weight was significantly decreased in group IV compared with group III (P<0.05). The mRNA levels of vascular endothelial growth factor, preproendo-thelin-1, interleukin-6 and tumor necrosis factor-alpha were significantly improved in group IV compared with group III (P<0.05). The immunofluorescence result showed that 6 weeks after administration ABM-MNCs could differentiate into pulmonary vascular endothelial cells. Conclusions: Six weeks after intratracheal administration, ABM-MNCs significantly improved the impairment caused by DMCT in a canine model of PH (ie, decreased pulmonary arteriolar narrowing, alveolar septum thickening and right ventricular hypertrophy, enhanced angiogenesis) and this provides a firm foundation for a clinical trial. (Circ J 2012; 76: 977-985)
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