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A Human Pluripotent Stem Cell-Based Screen for Smooth Muscle Cell Differentiation and Maturation Identifies Inhibitors of Intimal Hyperplasia.

Abstract：

:Contractile to synthetic phenotypic switching of smooth muscle cells (SMCs) contributes to stenosis in vascular disease and vascular transplants. To generate more contractile SMCs, we performed a high-throughput differentiation screen using a MYH11-NLuc-tdTomato human embryonic stem cell reporter cell line. We identified RepSox as a factor that promotes differentiation of MYH11-positive cells by promoting NOTCH signaling. RepSox induces SMCs to exhibit a more contractile phenotype than SMCs generated using PDGF-BB and TGF-β1, two factors previously used for SMC differentiation but which also cause intimal hyperplasia. In addition, RepSox inhibited intimal hyperplasia caused by contractile to synthetic phenotypic switching of SMCs in a rat balloon injury model. Thus, in addition to providing more contractile SMCs that could prove useful for constructing artificial blood vessels, this study suggests a strategy for identifying drugs for inhibiting intimal hyperplasia that act by driving contractile differentiation rather than inhibiting proliferation non-specifically.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Zhang J,McIntosh BE,Wang B,Brown ME,Probasco MD,Webster S,Duffin B,Zhou Y,Guo LW,Burlingham WJ,Kent C,Ferris M,Thomson JA

doi

10.1016/j.stemcr.2019.04.013

subject

Has Abstract

pub_date

2019-06-11 00:00:00

pages

1269-1281

issue

6

issn

2213-6711

pii

S2213-6711(19)30135-3

journal_volume

12

pub_type

杂志文章

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