Directed differentiation of embryonic origin-specific vascular smooth muscle subtypes from human pluripotent stem cells

Nat Protoc. 2014 Apr;9(4):929-38. doi: 10.1038/nprot.2014.059. Epub 2014 Mar 27.


Vascular smooth muscle cells (SMCs) arise from diverse developmental origins. Regional distribution of vascular diseases may, in part, be attributed to this inherent heterogeneity in SMC lineage. Therefore, systems for generating human SMC subtypes of distinct embryonic origins would represent useful platforms for studying the influence of SMC lineage on the spatial specificity of vascular disease. Here we describe how human pluripotent stem cells can be differentiated into distinct populations of SMC subtypes under chemically defined conditions. The initial stage (days 0-5 or 0-7) begins with the induction of three intermediate lineages: neuroectoderm, lateral plate mesoderm and paraxial mesoderm. Subsequently, these precursor lineages are differentiated into contractile SMCs (days 5-19+). At key stages, the emergence of lineage-specific markers confirms recapitulation of embryonic developmental pathways and generation of functionally distinct SMC subtypes. The ability to derive an unlimited supply of human SMCs will accelerate applications in regenerative medicine and disease modeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques / methods*
  • Cell Differentiation
  • Cell Lineage
  • Humans
  • Mesoderm / cytology
  • Muscle, Smooth, Vascular / cytology*
  • Pluripotent Stem Cells*