title: Smad signal pathway regulates angiogenesis via endothelial cell in an adipose-derived stromal cell/endothelial cell co-culture, 3D gel model.
abstract: Co-implantation of adipose-derived stromal cells (ASCs) and endothelial cells (ECs) can markedly expedite the formation of functional microvascular beds and provides possible methods for cell-based revascularization therapies to treat various diseases. Furthermore, we investigated the role of TGFβ/Smad signaling pathway for angiogenesis in a three-dimensional (3D) collagen gel model established in vitro with co-culture between ASCs and ECs. We found that angiogenesis was attenuated in the co-culture gels after inhibition of ALK5/Smad2/3 with SB431542. Genes coding for VEGF-A, VEGF-B, VE-ca, FGF-1, PDGF, BMP-4, and BMP-7 were significantly reduced in both mono-cultured and co-cultured ECs. Furthermore, the decrease in co-cultured ECs was prominent relative to mono-cultured ECs. Taken together, these findings suggest that in the co-culture between ASCs and ECs, TGFβ/Smad signal pathway regulates angiogenesis via ECs; moreover, the findings that the co-cultured ECs were regulated more significantly than mono-cultured ECs suggest that suppression of Smad signal pathway may regulate the paracrine secretion of ASCs to further modulate angiogenesis of ECs.
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Sirong
authors.initials: S
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China. yunfenglin@scu.edu.cn.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Lin
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004149:Dioxoles / Q000494:pharmacology; D015536:Down-Regulation; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D051379:Mice; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D051785:Smad Proteins; D042461:Vascular Endothelial Growth Factor A
keywords: Adipose stem cells; Angiogenesis; Endothelial cells; Smad signal pathway