ROCK suppression promotes differentiation and expansion of endothelial cells from embryonic stem cell-derived Flk1(+) mesodermal precursor cells
- Authors
- Joo, Hyung Joon; Choi, Dong-Kyu; Lim, Joon Seo; Park, Jin-Sung; Lee, Seung-Hun; Song, Sukhyun; Shin, Jennifer H.; Lim, Do-Sun; Kim, Injune; Hwang, Ki-Chul; Koh, Gou Young
- Issue Date
- 27-9월-2012
- Publisher
- AMER SOC HEMATOLOGY
- Citation
- BLOOD, v.120, no.13, pp.2733 - 2744
- Indexed
- SCIE
SCOPUS
- Journal Title
- BLOOD
- Volume
- 120
- Number
- 13
- Start Page
- 2733
- End Page
- 2744
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/107429
- DOI
- 10.1182/blood-2012-04-421610
- ISSN
- 0006-4971
- Abstract
- Successful differentiation and expansion of endothelial cells (ECs) from embryonic stem cell (ESC)-derived Flk1(+) mesodermal precursor cells (MPCs) requires supplementation of vascular endothelial growth factor-A (VEGF-A). While analyzing VEGF-A/VEGFR2 downstream signaling pathway that underlies the VEGF-A-induced differentiation and expansion of ECs, we fortuitously found that Rho-associated protein kinase (ROCK) inhibitor Y27632 profoundly promoted the differentiation and expansion of ECs from Flk1(+) MPCs while reducing the differentiation and expansion of mural cells. The ROCK suppression-induced expansion of ECs appears to have resulted from promotion of proliferation of ECs via activation of PI3-kinase-Akt signaling. The ECs obtained by the combination of ROCK suppression and VEGF-A supplementation faithfully expressed most pan-EC surface makers, and phenotypic analyses revealed that they were differentiated toward arterial EC. Further incubation of the ICAM2(+) ECs with Y27632 and VEGF-A for 2 days promoted expansion of ECs by 6.5-fold compared with those incubated with only VEGF-A. Importantly, the ROCK suppression- induced ECs displayed neovasculogenic abilities in vitro and in vivo. Thus, supplementation of ROCK inhibitor Y27632 along with VEGF-A in 2D Matrigel culture system provides a simple, efficient, and versatile method for obtaining ample amount of ESC-derived ECs at high purity suitable for use in therapeutic neovascularization. (Blood. 2012;120(13):2733-2744)
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.