Human embryonic stem cell-derived endothelial cell product injection attenuates cardiac remodeling in myocardial infarction.
cell therapy
hESC-ECP
immunomodulation
ligand–receptor interaction
myocardial infarction
scRNAseq
Journal
Frontiers in cardiovascular medicine
ISSN: 2297-055X
Titre abrégé: Front Cardiovasc Med
Pays: Switzerland
ID NLM: 101653388
Informations de publication
Date de publication:
2022
2022
Historique:
received:
25
05
2022
accepted:
16
09
2022
entrez:
27
10
2022
pubmed:
28
10
2022
medline:
28
10
2022
Statut:
epublish
Résumé
Mechanisms contributing to tissue remodeling of the infarcted heart following cell-based therapy remain elusive. While cell-based interventions have the potential to influence the cardiac healing process, there is little direct evidence of preservation of functional myocardium. The aim of the study was to investigate tissue remodeling in the infarcted heart following human embryonic stem cell-derived endothelial cell product (hESC-ECP) therapy. Following coronary artery ligation (CAL) to induce cardiac ischemia, we investigated infarct size at 1 day post-injection in media-injected controls (CALM, Human embryonic stem cell-derived endothelial cell product injection reduces the infarct area (CALM: 54.5 ± 5.0%, CALC: 21.3 ± 4.9%), and end-diastolic (CALM: 87.8 ± 8.9 uL, CALC: 63.3 ± 2.7 uL) and end-systolic ventricular volume (CALM: 56.4 ± 9.3 uL, CALC: 33.7 ± 2.6 uL). LRI analyses indicate an alternative immunomodulatory effect mediated Delivery of the live hESC-ECP following CAL modulates the wound healing response during acute pathological remodeling, reducing infarct area, and preserving functional myocardium in this relatively acute model. Potential intrinsic myocardial cellular/hESC-ECP interactions indicate that discreet immunomodulation could provide novel therapeutic avenues to improve cardiac outcomes following myocardial infarction.
Sections du résumé
Background
UNASSIGNED
Mechanisms contributing to tissue remodeling of the infarcted heart following cell-based therapy remain elusive. While cell-based interventions have the potential to influence the cardiac healing process, there is little direct evidence of preservation of functional myocardium.
Aim
UNASSIGNED
The aim of the study was to investigate tissue remodeling in the infarcted heart following human embryonic stem cell-derived endothelial cell product (hESC-ECP) therapy.
Materials and methods
UNASSIGNED
Following coronary artery ligation (CAL) to induce cardiac ischemia, we investigated infarct size at 1 day post-injection in media-injected controls (CALM,
Results
UNASSIGNED
Human embryonic stem cell-derived endothelial cell product injection reduces the infarct area (CALM: 54.5 ± 5.0%, CALC: 21.3 ± 4.9%), and end-diastolic (CALM: 87.8 ± 8.9 uL, CALC: 63.3 ± 2.7 uL) and end-systolic ventricular volume (CALM: 56.4 ± 9.3 uL, CALC: 33.7 ± 2.6 uL). LRI analyses indicate an alternative immunomodulatory effect mediated
Conclusion
UNASSIGNED
Delivery of the live hESC-ECP following CAL modulates the wound healing response during acute pathological remodeling, reducing infarct area, and preserving functional myocardium in this relatively acute model. Potential intrinsic myocardial cellular/hESC-ECP interactions indicate that discreet immunomodulation could provide novel therapeutic avenues to improve cardiac outcomes following myocardial infarction.
Identifiants
pubmed: 36299872
doi: 10.3389/fcvm.2022.953211
pmc: PMC9588936
doi:
Types de publication
Journal Article
Langues
eng
Pagination
953211Subventions
Organisme : British Heart Foundation
ID : CH/11/2/28733
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/17/27/32698
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M011542/1
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/14/3/30706
Pays : United Kingdom
Informations de copyright
Copyright © 2022 Spiroski, McCracken, Thomson, Magalhaes-Pinto, Lalwani, Newton, Miller, Bénézech, Hadoke, Brittan, Mountford, Beqqali, Gray and Baker.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Int J Mol Sci. 2021 Jan 19;22(2):
pubmed: 33478078
Cell Rep. 2020 Dec 8;33(10):108472
pubmed: 33296652
Arterioscler Thromb Vasc Biol. 2010 Jul;30(7):1389-97
pubmed: 20431067
Nat Methods. 2019 Dec;16(12):1289-1296
pubmed: 31740819
J Clin Invest. 2018 May 1;128(5):2127-2143
pubmed: 29664017
Nat Biotechnol. 2018 Jun;36(5):421-427
pubmed: 29608177
Bioinformatics. 2017 Apr 15;33(8):1179-1186
pubmed: 28088763
Nat Biotechnol. 2019 Aug;37(8):895-906
pubmed: 31375810
Nature. 2020 Jan;577(7790):405-409
pubmed: 31775156
Clin Exp Immunol. 2019 Oct;198(1):83-93
pubmed: 31119724
Arterioscler Thromb Vasc Biol. 2020 Jan;40(1):34-44
pubmed: 31510789
Nat Protoc. 2009;4(8):1184-91
pubmed: 19617889
Mol Ther. 2018 Jul 5;26(7):1669-1684
pubmed: 29703701
Cell Rep. 2020 Mar 3;30(9):3149-3163.e6
pubmed: 32130914
Eur Heart J. 2016 Jun 14;37(23):1789-98
pubmed: 27055812
Nat Rev Immunol. 2018 Dec;18(12):733-744
pubmed: 30228378
Eur Heart J. 2020 Mar 1;41(9):1024-1036
pubmed: 31242503
Circ Res. 2018 Jul 6;123(2):132-137
pubmed: 29976683
Nat Commun. 2016 Sep 01;7:12651
pubmed: 27582256
BMC Biol. 2016 Mar 17;14:21
pubmed: 26988708
Curr Opin Physiol. 2018 Feb;1:46-51
pubmed: 29876531
Cell. 2010 Sep 17;142(6):847-56
pubmed: 20850008
Circ Res. 2012 Sep 14;111(7):882-93
pubmed: 22821929
Springerplus. 2015 Jul 10;4:336
pubmed: 26185738
Br J Pharmacol. 2010 Aug;160(7):1577-9
pubmed: 20649561
Nat Immunol. 2015 Aug;16(8):819-828
pubmed: 26147686
Mol Ther. 2021 Feb 3;29(2):426-427
pubmed: 33472031
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
Proc Natl Acad Sci U S A. 2019 Oct 22;116(43):21673-21684
pubmed: 31591231
Circulation. 2011 Feb 1;123(4):e18-e209
pubmed: 21160056
PLoS One. 2009 Dec 31;4(12):e8443
pubmed: 20046878
Circulation. 2018 Feb 27;137(9):948-960
pubmed: 29167227
Nat Protoc. 2020 Apr;15(4):1484-1506
pubmed: 32103204