title: Generation of human vascular smooth muscle subtypes provides insight into embryological origin-dependent disease susceptibility.
abstract: Heterogeneity of embryological origins is a hallmark of vascular smooth muscle cells (SMCs) and may influence the development of vascular disease. Differentiation of human pluripotent stem cells (hPSCs) into developmental origin-specific SMC subtypes remains elusive. Here we describe a chemically defined protocol in which hPSCs were initially induced to form neuroectoderm, lateral plate mesoderm or paraxial mesoderm. These intermediate populations were further differentiated toward SMCs (>80% MYH11(+) and ACTA2(+)), which displayed contractile ability in response to vasoconstrictors and invested perivascular regions in vivo. Derived SMC subtypes recapitulated the unique proliferative and secretory responses to cytokines previously documented in studies using aortic SMCs of distinct origins. Notably, this system predicted increased extracellular matrix degradation by SMCs derived from lateral plate mesoderm, which was confirmed using rat aortic SMCs from corresponding origins. This differentiation approach will have broad applications in modeling origin-dependent disease susceptibility and in developing bioengineered vascular grafts for regenerative medicine.
authors.affiliation: The Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge, Cambridge, UK.
authors.forename: Christine
authors.initials: C
authors.lastname: Cheung
authors.forename: Andreia S
authors.initials: AS
authors.lastname: Bernardo
authors.forename: Matthew W B
authors.initials: MW
authors.lastname: Trotter
authors.forename: Roger A
authors.initials: RA
authors.lastname: Pedersen
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sinha
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004198:Disease Susceptibility; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008648:Mesoderm / Q000254:growth & development; D009131:Muscle, Smooth, Vascular / Q000196:embryology* / Q000254:growth & development*; D054258:Neural Plate / Q000254:growth & development; D039904:Pluripotent Stem Cells / Q000166:cytology; D051381:Rats; D044968:Regenerative Medicine; D014662:Vasoconstrictor Agents / Q000378:metabolism
chemical_list: D014662:Vasoconstrictor Agents