title: TGF-β1 induces the formation of vascular-like structures in embryoid bodies derived from human embryonic stem cells.
abstract: Human embryonic stem cells (ESCs) can differentiate into endothelial cells in response to stimuli from extracellular cytokines. Transforming growth factor (TGF)-β1 signaling is involved in stem cell renewal and vascular development. Previously, human ESCs were isolated from inner cell mass and a stable ESC line was developed. In the present study, the effects of extracellular TGF-β1 were investigated on human ESC-derived embryoid bodies (EB) in suspension. The structures of the EBs were analyzed with light and electron microscopy, while the cellular composition of the EBs was examined via the expression levels of specific markers. Vascular-like tubular structures and cardiomyocyte-like beating cells were observed in the EBs at day 3 and 8, respectively. The frequencies of vascular-like structures and beating cells in the TGF-β1 treated group were significantly higher compared with the control group (84.31 vs. 12.77%; P<0.001; 37.25 vs. 8.51%; P<0.001, respectively). Electron microscopy revealed the presence of lumens and gap junctions in the sections of the tubular structures. Semiquantitative polymerase chain reaction revealed elevated expression levels of CD31 and fetal liver kinase-1 in EBs cultured with TGF-β1. In addition, extensive staining of von Willebrand factor was observed in the vascular-like structures of TGF-β1-treated EBs. Therefore, the results of the present study may aid the understanding of the underlying mechanisms of human ESC differentiation and improve the methods of propagating specific cell types for the clinical therapy of cardiovascular diseases.
authors.affiliation: Department of Plastic Surgery, Provincial Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong 250014, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Plastic Surgery, Provincial Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong 250014, P.R. China.
authors.forename: DE-Jian
authors.initials: DJ
authors.lastname: Qian
authors.affiliation: Department of Gynecology and Obstetrics, Jinan Central Hospital, Jinan, Shandong 250013, P.R. China.
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Zhong
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai 200011, P.R. China.
authors.forename: Jun-Hong
authors.initials: JH
authors.lastname: Lu
authors.affiliation: Department of Plastic Surgery, Provincial Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong 250014, P.R. China.
authors.forename: Xiang-Kai
authors.initials: XK
authors.lastname: Guo
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai 200011, P.R. China.
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Cao
authors.affiliation: Department of Plastic Surgery, Provincial Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong 250014, P.R. China ; Medical Research Center, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, P.R. China.
authors.forename: Ju
authors.initials: J
authors.lastname: Liu
keywords: embryoid body; endothelial cell; human embryonic stem cell; transforming growth factor-β