Enhanced Function of Induced Pluripotent Stem Cell-Derived Endothelial Cells Through ESM1 Signaling.
ESM1
Endothelial cells
Induced pluripotent stem cells
Reprogramming
Vascular disease
Journal
Stem cells (Dayton, Ohio)
ISSN: 1549-4918
Titre abrégé: Stem Cells
Pays: England
ID NLM: 9304532
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
07
06
2018
revised:
14
09
2018
accepted:
07
10
2018
pubmed:
30
10
2018
medline:
3
4
2020
entrez:
30
10
2018
Statut:
ppublish
Résumé
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 2019;37:226-239.
Identifiants
pubmed: 30372556
doi: 10.1002/stem.2936
pmc: PMC6392130
doi:
Substances chimiques
ESM1 protein, human
0
Neoplasm Proteins
0
Proteoglycans
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
226-239Subventions
Organisme : British Heart Foundation
ID : PG/16/13/32024
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/15/23/31435
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/19/61/34586
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/16/8/31985
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_13075
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/13/18/30207
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_16057
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/14/78/31099
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/14/35/30813
Pays : United Kingdom
Informations de copyright
© 2018 The Authors. Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2018.
Références
Trends Cell Biol. 2010 Feb;20(2):92-101
pubmed: 19944606
Physiol Rev. 2004 Jul;84(3):869-901
pubmed: 15269339
Blood. 2010 Nov 11;116(19):4025-33
pubmed: 20705756
Cardiovasc Diabetol. 2017 Jul 27;16(1):95
pubmed: 28750645
Circ Res. 2017 Mar 3;120(5):756-758
pubmed: 28254795
Stem Cells. 2018 Jul;36(7):1033-1044
pubmed: 29569797
J Neuroinflammation. 2015 Jan 24;12:15
pubmed: 25616391
Stem Cells Transl Med. 2017 Apr;6(4):1168-1177
pubmed: 28233474
Hypertension. 2015 Apr;65(4):910-5
pubmed: 25712722
Angiology. 2018 Aug;69(7):609-616
pubmed: 29172652
Cell. 2007 Nov 30;131(5):861-72
pubmed: 18035408
Stem Cell Res. 2015 Jul;15(1):122-129
pubmed: 26042795
Stem Cells. 2017 Apr;35(4):952-966
pubmed: 28207177
Stem Cells. 2013 Jan;31(1):92-103
pubmed: 23079999
Tissue Eng Part C Methods. 2017 Aug;23(8):474-484
pubmed: 28622076
Curr Eye Res. 2015 Mar;40(3):321-31
pubmed: 24871583
Nat Biotechnol. 2010 Feb;28(2):161-6
pubmed: 20081865
Arterioscler Thromb Vasc Biol. 2014 Apr;34(4):913-20
pubmed: 24526696
Cell Res. 2011 Mar;21(3):518-29
pubmed: 21243013
Stem Cells Dev. 2015 Dec 1;24(23):2740-5
pubmed: 26413932
Front Cell Dev Biol. 2015 Feb 02;3:2
pubmed: 25699255
Cell Commun Signal. 2015 Jul 22;13:34
pubmed: 26198171
Stem Cells Cloning. 2014 Feb 15;7:19-29
pubmed: 24627642
Nucleic Acids Res. 2003 Jul 1;31(13):3651-3
pubmed: 12824386
Circ Res. 2014 Sep 26;115(8):709-20
pubmed: 25091710
Bioinformatics. 2002 Feb;18(2):333-4
pubmed: 11847087
Exp Cell Res. 1997 Aug 25;235(1):218-26
pubmed: 9281371
Am J Transl Res. 2013;5(1):21-35
pubmed: 23390563
Cell Signal. 2012 Oct;24(10):1940-9
pubmed: 22735811
Nat Protoc. 2012 Nov;7(11):2013-21
pubmed: 23080273
Stem Cell Res Ther. 2015 Dec 30;6:261
pubmed: 26718617
Am J Physiol Heart Circ Physiol. 2010 Nov;299(5):H1365-73
pubmed: 20802140
J Cell Sci. 2008 Oct 15;121(Pt 20):3317-24
pubmed: 18796538
Stem Cell Res. 2012 Jan;8(1):85-96
pubmed: 22099023
Indian J Pharmacol. 2014 Nov-Dec;46(6):579-83
pubmed: 25538326
Phys Ther. 2008 Nov;88(11):1322-35
pubmed: 18801863
Histochem Cell Biol. 2004 Nov;122(5):477-83
pubmed: 15558296
Circ Res. 2014 Aug 29;115(6):581-90
pubmed: 25057127
FEBS Lett. 2014 Apr 17;588(8):1322-30
pubmed: 24548564
Int J Chron Obstruct Pulmon Dis. 2016 Dec 12;11:3179-3187
pubmed: 28003744
Stem Cells. 2017 Apr;35(4):909-919
pubmed: 28248004
Arterioscler Thromb Vasc Biol. 2011 Nov;31(11):e72-9
pubmed: 21836062
Biomed Rep. 2015 May;3(3):279-283
pubmed: 26137222
Stem Cells Transl Med. 2017 Aug;6(8):1673-1683
pubmed: 28628273
J Mol Cell Cardiol. 1994 Jul;26(7):861-8
pubmed: 7966354
Nat Cell Biol. 2011 May;13(5):497-505
pubmed: 21540845
Arterioscler Thromb Vasc Biol. 2014 Jan;34(1):177-86
pubmed: 24158517
Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):827-34
pubmed: 20081116