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iPSC-derived Vascular Cells Go with the Flow!

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Review of “Exposure of iPSC-Derived Vascular Endothelial and Smooth Muscle Cells in Co-Culture to Hemodynamics Induces Primary Vascular Cell-Like Phenotypes” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Cells derived from pluripotent stem cell (PSC) sources, such as induced pluripotent stem cells (iPSCs), often suffer from a lack of functional maturity that ultimately reduces their utility post-transplantation. Now, a team of researchers from the laboratory of Brian R. Wamhoff (HemoShear Therapeutics, LLC, Charlottesville, Virginia, USA) has demonstrated that exposing a coculture of immature vascular endothelial (EC) and smooth muscle (SMC) cells differentiated from iPSCs to vascular blood flow hemodynamics [1-3] can improve cell maturity to a level similar to primary cells. 

Could this new STEM CELLS Translational Medicine study represent the first step in creating a patient- and disease- specific system to model rare vascular diseases and develop new therapeutic approaches [4]?

Collado et al. first measured shear stress profiles generated from magnetic resonance imaging of the human vasculature and applied them to an EC/SMC vascular-like coculture system. Under the influence of hemodynamic parameters derived from healthy patients, iPSC-derived ECs and SMCs reacted in a similar manner to their primary human aortic counterparts. The improvement mediated by the addition of blood flow hemodynamics included a marked maturation in the functionality of iPSC-derived ECs (enhanced acetylated-low-density lipoprotein (LDL) uptake) and SMCs (enhanced contractile protein marker expression).

Encouragingly, the study also demonstrated similarities between the responses of iPSC-derived and primary vascular co-cultures under less healthy conditions, such as those associated with vascular disease. Such conditions included exposure to atherosclerosis-like hemodynamics, the addition of oxidized LDL and TNFα to promote the advanced inflammatory conditions associated with atherogenesis, and under conditions of disrupted TGFβ signaling, which is associated with many disease states [5].  

Overall, this suggests that iPSC-derived cells can be employed to construct a suitable model of the healthy and diseased vascular system given the presence of adequate hemodynamics and heterotypic cell-cell communication. Hopefully, this convenient system may allow users to screen for drugs and search for new therapeutic strategies in a disease- and patient-specific manner.

Go with the flow and keep tuned to the Stem Cells Portal!

References

  1. Hastings NE, Simmers MB, McDonald OG, et al. Atherosclerosis-prone hemodynamics differentially regulates endothelial and smooth muscle cell phenotypes and promotes pro-inflammatory priming. Am J Physiol Cell Physiol 2007;293:C1824-1833.
  2. Hastings NE, Feaver RE, Lee MY, et al. Human IL-8 regulates smooth muscle cell VCAM-1 expression in response to endothelial cells exposed to atheroprone flow. Arterioscler Thromb Vasc Biol 2009;29:725-731.
  3. Cole BK, Simmers MB, Feaver R, et al. An In Vitro Cynomolgus Vascular Surrogate System for Preclinical Drug Assessment and Human Translation. Arterioscler Thromb Vasc Biol 2015;35:2185-2195.
  4. Collado MS, Cole BK, Figler RA, et al. Exposure of Induced Pluripotent Stem Cell-Derived Vascular Endothelial and Smooth Muscle Cells in Coculture to Hemodynamics Induces Primary Vascular Cell-Like Phenotypes. STEM CELLS Translational Medicine 2017;6:1673-1683.
  5. Gordon KJ and Blobe GC. Role of transforming growth factor-beta superfamily signaling pathways in human disease. Biochim Biophys Acta 2008;1782:197-228.