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Modeling elastin-associated vasculopathy with patient induced pluripotent stem cells and tissue engineering

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Abstract

Elastin-associated vasculopathies are life-threatening conditions of blood vessel dysfunction. The extracellular matrix protein elastin endows the recoil and compliance required for physiologic arterial function, while disruption of function can lead to aberrant vascular smooth muscle cell proliferation manifesting through stenosis, aneurysm, or vessel dissection. Although research efforts have been informative, they remain incomplete as no viable therapies exist outside of a heart transplant. Induced pluripotent stem cell technology may be uniquely suited to address current obstacles as these present a replenishable supply of patient-specific material with which to study disease. The following review will cover the cutting edge in vascular smooth muscle cell modeling of elastin-associated vasculopathy, and aid in the development of human disease modeling and drug screening approaches to identify potential treatments. Vascular proliferative disease can affect up to 50% of the population throughout the world, making this a relevant and critical area of research for therapeutic development.

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Abbreviations

VSMC:

Vascular smooth muscle cell

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Acknowledgements

We appreciate the support from Muhammad Riaz (Ph.D.) and Luke Batty (M.S.). This work was supported by NIH 1K02HL101990-01, 1R01HL116705-01, and Connecticut’s Regenerative Medicine Research Fund (CRMRF) 12-SCB-YALE-06 and 15-RMB-YALE-08 (all to Y.Q.). Work was also supported by an NIH Institutional Pre-Doctoral Pharmacology Training Program Fellowship T32-GM0007324 (M.E.) directed by Dr. Anton Bennett at Yale.

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Authors and Affiliations

  1. Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, Yale Cardiovascular Research Center, New Haven, CT, 06511, USA

    Matthew W. Ellis, Jiesi Luo & Yibing Qyang

  2. Department of Cellular and Molecular Physiology, Yale University, New Haven, CT, 06519, USA

    Matthew W. Ellis

  3. Yale Stem Cell Center, New Haven, CT, 06520, USA

    Jiesi Luo & Yibing Qyang

  4. Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, 06520, USA

    Yibing Qyang

  5. Department of Pathology, Yale School of Medicine, New Haven, CT, 06520, USA

    Yibing Qyang

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  1. Matthew W. Ellis
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  2. Jiesi Luo
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Correspondence to Yibing Qyang.

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Ellis, M.W., Luo, J. & Qyang, Y. Modeling elastin-associated vasculopathy with patient induced pluripotent stem cells and tissue engineering. Cell. Mol. Life Sci. 76, 893–901 (2019). https://doi.org/10.1007/s00018-018-2969-7

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