ROCK suppression promotes differentiation and expansion of endothelial cells from embryonic stem cell-derived Flk1(+) mesodermal precursor cells

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dc.contributor.authorJoo, Hyung-Joonko
dc.contributor.authorChoi, Dong-Kyuko
dc.contributor.authorLim, Joon-Seoko
dc.contributor.authorPark, Jin-Sungko
dc.contributor.authorLee, Seung-Hunko
dc.contributor.authorSong, Suk-Hyunko
dc.contributor.authorShin, Jennifer Hyunjongko
dc.contributor.authorLim, Do-Sunko
dc.contributor.authorKim, In-Juneko
dc.contributor.authorHwang, Ki-Chulko
dc.contributor.authorKoh, Gou-Youngko
dc.date.accessioned2013-03-12T12:17:12Z-
dc.date.available2013-03-12T12:17:12Z-
dc.date.created2013-02-14-
dc.date.created2013-02-14-
dc.date.issued2012-09-
dc.identifier.citationBLOOD, v.120, no.13, pp.2733 - 2744-
dc.identifier.issn0006-4971-
dc.identifier.urihttp://hdl.handle.net/10203/102289-
dc.description.abstractSuccessful 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)-
dc.languageEnglish-
dc.publisherAMER SOC HEMATOLOGY-
dc.subjectVASCULAR PROGENITORS-
dc.subjectIN-VITRO-
dc.subjectSPROUTING ANGIOGENESIS-
dc.subjectMICROFLUIDIC PLATFORM-
dc.subjectVEGF-
dc.subjectPATHWAY-
dc.subjectVASCULOGENESIS-
dc.subjectARTERIAL-
dc.subjectKINASES-
dc.subjectPROTEIN-
dc.titleROCK suppression promotes differentiation and expansion of endothelial cells from embryonic stem cell-derived Flk1(+) mesodermal precursor cells-
dc.typeArticle-
dc.identifier.wosid000311615800029-
dc.identifier.scopusid2-s2.0-84866865798-
dc.type.rimsART-
dc.citation.volume120-
dc.citation.issue13-
dc.citation.beginningpage2733-
dc.citation.endingpage2744-
dc.citation.publicationnameBLOOD-
dc.identifier.doi10.1182/blood-2012-04-421610-
dc.contributor.localauthorShin, Jennifer Hyunjong-
dc.contributor.localauthorKim, In-June-
dc.contributor.localauthorKoh, Gou-Young-
dc.contributor.nonIdAuthorLim, Do-Sun-
dc.contributor.nonIdAuthorHwang, Ki-Chul-
dc.type.journalArticleArticle-
dc.subject.keywordPlusVASCULAR PROGENITORS-
dc.subject.keywordPlusIN-VITRO-
dc.subject.keywordPlusSPROUTING ANGIOGENESIS-
dc.subject.keywordPlusMICROFLUIDIC PLATFORM-
dc.subject.keywordPlusVEGF-
dc.subject.keywordPlusPATHWAY-
dc.subject.keywordPlusVASCULOGENESIS-
dc.subject.keywordPlusARTERIAL-
dc.subject.keywordPlusKINASES-
dc.subject.keywordPlusPROTEIN-
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