title: Therapeutic effectiveness of bone marrow-derived mesenchymal stem cell administration against acute pulmonary thromboembolism in a mouse model.
abstract: BACKGROUND
  Acute pulmonary thromboembolism (APTE) is a common clinical condition associated with significant morbidity and mortality. Although promising, bone marrow-derived mesenchymal stem cell (BMSC) treatment for thrombus resolution remains controversial. The therapeutic effectiveness of BMSC against APTE has not been evaluated. This study aims to determine whether BMSCs administration is effective in mouse model.
  
  
  METHODS
  Therapeutic efficacy of female and male BMSCs were evaluated by applying serial sectioning analysis method for the whole lungs of APTE mice and calculating each thrombus size in volume. Plasmid construction and stable transfection were used to manipulate expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in both genders of BMSCs. Western blot were performed to detect GAPDH and urokinase plasminogen activator expression in BMSCs.
  
  
  RESULTS
  Our data showed, 1) compared with non-serial sectioning method, the serial sectioning method detected more thrombi, larger size ranges of thrombus area, and the volume of each individual thrombus. 2) BMSCs significantly decreased the thrombi size in APTE mice, with female BMSCs superior to male ones. 3) female BMSCs showed a higher GAPDH protein level and manipulations of GAPDH expression in female or male BMSCs profoundly affected their therapeutic efficacies as well as urokinase plasminogen activator expression.
  
  
  CONCLUSIONS
  This study indicates serial-sectioning analysis method is necessary for evaluating APTE and provides strong evidences for BMSCs possessing therapeutic effectiveness against APTE, with female BMSCs superior to male counterparts. GAPDH played a critical role in the superior function of female BMSCs, possibly by regulating the expression of urokinase plasminogen activator.
authors.affiliation: Department of Pathophysiology, Tongji School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Pulmonary Diseases of Ministry of Health, Tongji School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Peng
authors.affiliation: Key Laboratory of Pulmonary Diseases of Ministry of Health, Tongji School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Jiansha
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Tongji School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Pulmonary Diseases of Ministry of Health, Tongji School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Xiangyuan
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Pathophysiology, Tongji School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Pulmonary Diseases of Ministry of Health, Tongji School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Rubin
authors.initials: R
authors.lastname: Tan
authors.affiliation: Department of Pathophysiology, Tongji School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Pulmonary Diseases of Ministry of Health, Tongji School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Physiology, Capital Medical University, Beijing 100730, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Rongshuai
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Gu
authors.affiliation: Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Respiratory Medicine, Beijing Hospital, Ministry of Health, Beijing 100730, China. Electronic address: cyh-birm@263.net.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Tongji School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Pulmonary Diseases of Ministry of Health, Tongji School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: qinghuaa@mails.tjmu.edu.cn.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Hu
mesh_terms: D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011655:Pulmonary Embolism / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D014162:Transfection; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D014568:Urokinase-Type Plasminogen Activator
keywords: Acute pulmonary thromboembolism; Bone marrow-derived mesenchymal stem cell; Gender difference; Glyceraldehyde-3-phosphate dehydrogenase; Serial sectioning