title: VCAM-1+ placenta chorionic villi-derived mesenchymal stem cells display potent pro-angiogenic activity.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) represent a heterogeneous cell population that is promising for regenerative medicine. The present study was designed to assess whether VCAM-1 can be used as a marker of MSC subpopulation with superior angiogenic potential.
  
  
  METHODS
  MSCs were isolated from placenta chorionic villi (CV). The VCAM-1(+/-) CV-MSCs population were separated by Flow Cytometry and subjected to a comparative analysis for their angiogenic properties including angiogenic genes expression, vasculo-angiogenic abilities on Matrigel in vitro and in vivo, angiogenic paracrine activities, cytokine array, and therapeutic angiogenesis in vascular ischemic diseases.
  
  
  RESULTS
  Angiogenic genes, including HGF, ANG, IL8, IL6, VEGF-A, TGFβ, MMP2 and bFGF, were up-regulated in VCAM-1(+)CV-MSCs. Consistently, angiogenic cytokines especially HGF, IL8, angiogenin, angiopoitin-2, μPAR, CXCL1, IL-1β, IL-1α, CSF2, CSF3, MCP-3, CTACK, and OPG were found to be significantly increased in VCAM-1(+) CV-MSCs. Moreover, VCAM-1(+)CV-MSCs showed remarkable vasculo-angiogenic abilities by angiogenesis analysis with Matrigel in vitro and in vivo and the conditioned medium of VCAM-1(+) CV-MSCs exerted markedly pro-proliferative and pro-migratory effects on endothelial cells compared to VCAM-1(-)CV-MSCs. Finally, transplantation of VCAM-1(+)CV-MSCs into the ischemic hind limb of BALB/c nude mice resulted in a significantly functional improvement in comparison with VCAM-1(-)CV-MSCs transplantation.
  
  
  CONCLUSIONS
  VCAM-1(+)CV-MSCs possessed a favorable angiogenic paracrine activity and displayed therapeutic efficacy on hindlimb ischemia. Our results suggested that VCAM-1(+)CV-MSCs may represent an important subpopulation of MSC for efficient therapeutic angiogenesis.
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No.288, Nanjing Road, Heping District, Tianjin, 300020, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Du
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No.288, Nanjing Road, Heping District, Tianjin, 300020, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No.288, Nanjing Road, Heping District, Tianjin, 300020, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chi
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No.288, Nanjing Road, Heping District, Tianjin, 300020, China.
authors.forename: Fengxia
authors.initials: F
authors.lastname: Ma
authors.affiliation: Beijing Institute of Health and Stem Cells, No.1 Kangding Road, BDA, Beijing, 100176, China.
authors.forename: Zongjin
authors.initials: Z
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No.288, Nanjing Road, Heping District, Tianjin, 300020, China.
authors.forename: Shaoguang
authors.initials: S
authors.lastname: Yang
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No.288, Nanjing Road, Heping District, Tianjin, 300020, China.
authors.forename: Baoquan
authors.initials: B
authors.lastname: Song
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No.288, Nanjing Road, Heping District, Tianjin, 300020, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Cui
authors.affiliation: National Engineering Research Center of Cell Products, No.80, Fourth Avenue, TEDA, Tianjin, 300457, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Ma
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No.288, Nanjing Road, Heping District, Tianjin, 300020, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No.288, Nanjing Road, Heping District, Tianjin, 300020, China.
authors.forename: Jianjian
authors.initials: J
authors.lastname: Tian
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No.288, Nanjing Road, Heping District, Tianjin, 300020, China.
authors.forename: Zhouxin
authors.initials: Z
authors.lastname: Yang
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No.288, Nanjing Road, Heping District, Tianjin, 300020, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Feng
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No.288, Nanjing Road, Heping District, Tianjin, 300020, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No.288, Nanjing Road, Heping District, Tianjin, 300020, China.
authors.forename: Shihong
authors.initials: S
authors.lastname: Lu
authors.affiliation: Beijing Institute of Health and Stem Cells, No.1 Kangding Road, BDA, Beijing, 100176, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liang
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No.288, Nanjing Road, Heping District, Tianjin, 300020, China. zhibohan@163.com.
authors.forename: Zhi-Bo
authors.initials: ZB
authors.lastname: Han
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No.288, Nanjing Road, Heping District, Tianjin, 300020, China. hanzhongchao@hotmail.com.|Beijing Institute of Health and Stem Cells, No.1 Kangding Road, BDA, Beijing, 100176, China. hanzhongchao@hotmail.com.|National Engineering Research Center of Cell Products, No.80, Fourth Avenue, TEDA, Tianjin, 300457, China. hanzhongchao@hotmail.com.
authors.forename: Zhong-Chao
authors.initials: ZC
authors.lastname: Han
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D012039:Regional Blood Flow; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D019010:Vascular Cell Adhesion Molecule-1
keywords: Angiogenesis; Mesenchymal stem cells; Paracrine; Placenta; Vascular cell adhesion molecule-1 (CD106)