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 3mg/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; (III) PH group; (IV) PH+ABM-MNCs group. Six weeks after injection of cells (10⁷), 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, preproendothelin-1, interleukin-6 and tumor necrosis factor-α 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.
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 3mg/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; (III) PH group; (IV) PH+ABM-MNCs group. Six weeks after injection of cells (10⁷), 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, preproendothelin-1, interleukin-6 and tumor necrosis factor-α 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.
Authors: Ling Yan; Xinping Chen; Megha Talati; Bethany Womack Nunley; Santhi Gladson; Tom Blackwell; Joy Cogan; Eric Austin; Ferrin Wheeler; James Loyd; James West; Rizwan Hamid Journal: Am J Respir Crit Care Med Date: 2016-04-15 Impact factor: 21.405
Authors: Colin M Suen; Duncan J Stewart; Joshua Montroy; Christopher Welsh; Brendan Levac; Neil Wesch; Alexander Zhai; Dean Fergusson; Lauralyn McIntyre; Manoj M Lalu Journal: Stem Cell Res Ther Date: 2019-03-06 Impact factor: 6.832