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A Human Pluripotent Stem Cell-Based Screen for Smooth Muscle Cell Differentiation and Maturation Identifies
Jue Zhang1, Brian E McIntosh1, Bowen Wang2
1Regenerative Biology, Morgridge Institute for Research, 330 North Orchard Street, Madison, WI 53715, USA.
Stem Cell Reports
|May 14, 2019
Summary
RepSox promotes smooth muscle cell differentiation into contractile cells, offering a new strategy for vascular disease and artificial vessel construction. This factor also inhibits intimal hyperplasia.
Area of Science:
- Vascular biology
- Stem cell differentiation
- Regenerative medicine
Background:
- Smooth muscle cell (SMC) phenotypic switching contributes to vascular diseases like stenosis.
- Existing methods for SMC differentiation can induce unwanted intimal hyperplasia.
Purpose of the Study:
- To identify factors promoting contractile SMC differentiation.
- To find new therapeutic strategies for vascular diseases by targeting SMC phenotype.
Main Methods:
- High-throughput differentiation screen using a MYH11-NLuc-tdTomato human embryonic stem cell reporter line.
- Treatment with identified factors (RepSox) and comparison with existing factors (PDGF-BB, TGF-β1).
- Assessment of intimal hyperplasia in a rat balloon injury model.
Main Results:
- RepSox was identified as a factor promoting SMC differentiation via NOTCH signaling.
- RepSox-induced SMCs exhibited a more contractile phenotype compared to those differentiated with PDGF-BB/TGF-β1.
- RepSox significantly inhibited intimal hyperplasia in vivo.
Conclusions:
- RepSox promotes the generation of contractile SMCs, useful for artificial blood vessel construction.
- RepSox offers a novel therapeutic strategy for inhibiting intimal hyperplasia by promoting contractile differentiation.
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