title: Effects of autologous bone marrow mononuclear cells implantation in canine model of pulmonary hypertension.
abstract: 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).
  
  
  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.affiliation: Central Research Laboratory, The Second Hospital of Shandong University, Jinan, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Luan
authors.forename: Zhao-Hua
authors.initials: ZH
authors.lastname: Zhang
authors.forename: De-E
authors.initials: DE
authors.lastname: Wei
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Yi-Biao
authors.initials: YB
authors.lastname: Wang
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002454:Cell Differentiation; D002469:Cell Separation / Q000379:methods; D058948:Cell Tracking / Q000379:methods; D004195:Disease Models, Animal; D004285:Dogs; D042783:Endothelial Cells / Q000378:metabolism / Q000637:transplantation*; D019332:Endothelin-1 / Q000235:genetics; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D017380:Hypertrophy, Right Ventricular / Q000503:physiopathology / Q000601:surgery; D015850:Interleukin-6 / Q000235:genetics; D016686:Monocrotaline / Q000031:analogs & derivatives; D018919:Neovascularization, Physiologic; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000009:adverse effects; D013997:Time Factors; D014182:Transplantation, Autologous; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D016278:Ventricular Function, Right
chemical_list: D019332:Endothelin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C014114:monocrotaline pyrrole; D016686:Monocrotaline