Enhanced Function of Induced Pluripotent Stem Cell-Derived Endothelial Cells Through ESM1 Signaling

Marta Vilà-González, Sophia Kelaini, Corey Magee, Rachel Caines, David Campbell, Magdalini Eleftheriadou, Amy Cochrane, Daiana Drehmer, Marianna Tsifaki, Karla O'Neill, Edoardo Pedrini, Chunbo Yang, Reinhold Medina, Denise McDonald, David Simpson, Anna Zampetaki, Lingfang Zeng, David Grieve, Noemi Lois, Alan W StittAndriana Margariti*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)
463 Downloads (Pure)


The mortality rate for (cardio)-vascular disease is one of the highest in the world, so a healthy functional endothelium is of outmost importance against vascular disease. In this study, human induced pluripotent stem (iPS) cells were reprogrammed from 1 ml blood of healthy donors and subsequently differentiated into endothelial cells (iPS-ECs) with typical EC characteristics. This research combined iPS cell technologies and next-generation sequencing to acquire an insight into the transcriptional regulation of iPS-ECs. We identified endothelial cell-specific molecule 1 (ESM1) as one of the highest expressed genes during EC differentiation, playing a key role in EC enrichment and function by regulating connexin 40 (CX40) and eNOS. Importantly, ESM1 enhanced the iPS-ECs potential to improve angiogenesis and neovascularisation in in vivo models of angiogenesis and hind limb ischemia. These findings demonstrated for the first time that enriched functional ECs are derived through cell reprogramming and ESM1 signaling, opening the horizon for drug screening and cell-based therapies for vascular diseases. Therefore, this study showcases a new approach for enriching and enhancing the function of induced pluripotent stem (iPS) cell-derived ECs from a very small amount of blood through ESM1 signaling, which greatly enhances their functionality and increases their therapeutic potential. Stem Cells 2018.

Original languageEnglish
Pages (from-to)226
JournalStem Cells
Issue number2
Early online date29 Oct 2018
Publication statusPublished - 17 Nov 2018
Externally publishedYes

Bibliographical note

© 2018 The Authors. Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2018.


  • Endothelial cells
  • ESM1
  • Induced pluripotent stem cells
  • Reprogramming
  • Vascular disease

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology


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