title: Platelet-mediated mesenchymal stem cells homing to the lung reduces monocrotaline-induced rat pulmonary hypertension.
abstract: Bone marrow mesenchymal stem cell (BM-MSC) transplantation has been suggested to be a promising method for the treatment of pulmonary arterial hypertension (PAH), a fatal disease currently without effective preventive/therapeutic strategies. However, the detailed mechanisms underlying BM-MSC therapy are largely unknown. We designed the present study to test the hypothesis that circulating platelets facilitate BM-MSC homing to the lung vasculature in a rat model of PAH induced by monocrotalin (MCT). A single subcutaneous administration of MCT induced a marked rise in right ventricular systolic pressure (RVSP) and the weight ratio of right to left ventricle plus septum (RV/LV+S) 3 weeks after injection. The injection of MSCs via tail vein 3 days after MCT significantly reduced the increase of RVSP and RV/LV+S. The fluorescence-labeled MSCs injected into the PAH rat circulation were found mostly distributed in the lungs, particularly on the pulmonary vascular wall, whereas cell homing was abolished by an anti-P-selectin antibody and the GPIIb/IIIa inhibitor tirofiban. Furthermore, using an in vitro flow chamber, we demonstrated that MSC adhesion to the major extracellular matrix collagen was facilitated by platelets and their P-selectin and GPIIb/IIIa. Therefore, the current study suggested that platelet-mediated MSC homing prevented the aggravation of MCT-induced rat PAH, via P-selectin and GPIIb/IIIa-mediated mechanisms.
authors.affiliation: Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.forename: Xing Hui
authors.initials: XH
authors.lastname: Song
authors.forename: Pu
authors.initials: P
authors.lastname: Liu
authors.forename: Chun Lai
authors.initials: CL
authors.lastname: Zeng
authors.forename: Zhang Sen
authors.initials: ZS
authors.lastname: Huang
authors.forename: Lin Jing
authors.initials: LJ
authors.lastname: Zhu
authors.forename: Yang Zi
authors.initials: YZ
authors.lastname: Jiang
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Ouyang
authors.forename: Hu
authors.initials: H
authors.lastname: Hu
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D001794:Blood Pressure; D001854:Bone Marrow Cells / Q000166:cytology; D065627:Familial Primary Pulmonary Hypertension; D006352:Heart Ventricles / Q000503:physiopathology; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000628:therapy*; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D016686:Monocrotaline / Q000633:toxicity; D019007:P-Selectin / Q000276:immunology / Q000378:metabolism; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000906:Antibodies; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D016686:Monocrotaline; D000077466:Tirofiban