Open AccessEnhanced Function of Induced Pluripotent Stem Cell‐Derived Endothelial Cells Through ESM1 Signaling
Author(s) -
VilàGonzález Marta,
Kelaini Sophia,
Magee Corey,
Caines Rachel,
Campbell David,
Eleftheriadou Magdalini,
Cochrane Amy,
Drehmer Daiana,
Tsifaki Marianna,
O'Neill Karla,
Pedrini Edoardo,
Yang Chunbo,
Medina Reinhold,
McDonald Denise,
Simpson David,
Zampetaki Anna,
Zeng Lingfang,
Grieve David,
Lois Noemi,
Stitt Alan W.,
Margariti Andriana
Publication year - 2019
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2936
Subject(s) - induced pluripotent stem cell , biology , angiogenesis , endothelial stem cell , reprogramming , stem cell , microbiology and biotechnology , endothelium , vasculogenesis , embryonic stem cell , cell , cancer research , progenitor cell , endocrinology , genetics , gene , in vitro
Abstract 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. S tem C ells 2019;37:226–239