title: Smooth muscle progenitor cells from peripheral blood promote the neovascularization of endothelial colony-forming cells.
abstract: Proangiogenic cell therapy using autologous progenitors is a promising strategy for treating ischemic disease. Considering that neovascularization is a harmonized cellular process that involves both endothelial cells and vascular smooth muscle cells, peripheral blood-originating endothelial colony-forming cells (ECFCs) and smooth muscle progenitor cells (SMPCs), which are similar to mature endothelial cells and vascular smooth muscle cells, could be attractive cellular candidates to achieve therapeutic neovascularization. We successfully induced populations of two different vascular progenitor cells (ECFCs and SMPCs) from adult peripheral blood. Both progenitor cell types expressed endothelial-specific or smooth muscle-specific genes and markers, respectively. In a protein array focused on angiogenic cytokines, SMPCs demonstrated significantly higher expression of bFGF, EGF, TIMP2, ENA78, and TIMP1 compared to ECFCs. Conditioned medium from SMPCs and co-culture with SMPCs revealed that SMPCs promoted cell proliferation, migration, and the in vitro angiogenesis of ECFCs. Finally, co-transplantation of ECFCs and SMPCs induced robust in vivo neovascularization, as well as improved blood perfusion and tissue repair, in a mouse ischemic hindlimb model. Taken together, we have provided the first evidence of a cell therapy strategy for therapeutic neovascularization using two different types of autologous progenitors (ECFCs and SMPCs) derived from adult peripheral blood.
authors.affiliation: Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Joo
authors.affiliation: Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Ha-Rim
authors.initials: HR
authors.lastname: Seo
authors.affiliation: Department of Mechanical Engineering, Korea University, Seoul, Republic of Korea.
authors.forename: Hyo Eun
authors.initials: HE
authors.lastname: Jeong
authors.affiliation: Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Seung-Cheol
authors.initials: SC
authors.lastname: Choi
authors.affiliation: Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Cheol Woong
authors.initials: CW
authors.lastname: Yu
authors.affiliation: Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Soon Jun
authors.initials: SJ
authors.lastname: Hong
authors.affiliation: Department of Mechanical Engineering, Korea University, Seoul, Republic of Korea.
authors.forename: Seok
authors.initials: S
authors.lastname: Chung
authors.affiliation: Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul, Republic of Korea. Electronic address: dslmd@kumc.or.kr.
authors.forename: Do-Sun
authors.initials: DS
authors.lastname: Lim
mesh_terms: D000328:Adult; D000818:Animals; D002470:Cell Survival; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology*; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007511:Ischemia / Q000628:therapy; D051379:Mice; D023421:Models, Animal; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D018919:Neovascularization, Physiologic; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned
keywords: Adult peripheral blood; Endothelial-colony forming cell; Ischemic hindlimb; Neovascularization; Smooth muscle progenitor cell