Cardiomyocyte Transplantation after Myocardial Infarction Alters the Immune Response in the Heart.
Animals
Antigens, CD
/ immunology
Antigens, Differentiation, Myelomonocytic
/ immunology
Disease Models, Animal
Gene Expression Profiling
Heart
/ physiology
Macrophages
/ immunology
Mice
Mice, Inbred C57BL
Monocytes
/ immunology
Myocardial Infarction
/ physiopathology
Myocardium
/ immunology
Myocytes, Cardiac
/ immunology
Receptors, CCR2
/ immunology
T-Lymphocytes, Regulatory
/ immunology
cardiomyocytes
immune response
infarction
translation
transplantation
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
03 08 2020
03 08 2020
Historique:
received:
14
06
2020
revised:
29
07
2020
accepted:
31
07
2020
entrez:
7
8
2020
pubmed:
7
8
2020
medline:
11
3
2021
Statut:
epublish
Résumé
We investigated the influence of syngeneic cardiomyocyte transplantation after myocardial infarction (MI) on the immune response and cardiac function. Methods and Results: We show for the first time that the immune response is altered as a result of syngeneic neonatal cardiomyocyte transplantation after MI leading to improved cardiac pump function as observed by magnetic resonance imaging in C57BL/6J mice. Interestingly, there was no improvement in the capillary density as well as infarct area as observed by CD31 and Sirius Red staining, respectively. Flow cytometric analysis revealed a significantly different response of monocyte-derived macrophages and regulatory T cells after cell transplantation. Interestingly, the inhibition of monocyte infiltration accompanied by cardiomyocyte transplantation diminished the positive effect of cell transplantation alone. The number of CD68+ macrophages in the remote area of the heart observed after four weeks was also different between the groups. Transcriptome analysis showed several changes in the gene expression involving circadian regulation, mitochondrial metabolism and immune responses after cardiomyocyte transplantation. Conclusion: Our work shows that cardiomyocyte transplantation alters the immune response after myocardial infarction with the recruited monocytes playing a role in the beneficial effect of cell transplantation. It also paves the way for further optimization of the efficacy of cardiomyocyte transplantation and their successful translation in the clinic.
Identifiants
pubmed: 32756334
pii: cells9081825
doi: 10.3390/cells9081825
pmc: PMC7465503
pii:
doi:
Substances chimiques
Antigens, CD
0
Antigens, Differentiation, Myelomonocytic
0
CD68 protein, mouse
0
Ccr2 protein, mouse
0
Receptors, CCR2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Références
Circulation. 2002 Apr 9;105(14):1720-6
pubmed: 11940553
Science. 2013 Sep 27;341(6153):1483-8
pubmed: 23970558
Inflamm Regen. 2020 Jan 13;40:1
pubmed: 31938077
Nucleic Acids Res. 2016 Jul 8;44(W1):W147-53
pubmed: 27190236
Chronobiol Int. 1999 Sep;16(5):581-622
pubmed: 10513884
Blood. 2006 Jan 1;107(1):367-72
pubmed: 16141348
Circ Res. 2007 Aug 31;101(5):484-92
pubmed: 17641227
J Biol Chem. 2006 Aug 25;281(34):24254-69
pubmed: 16798731
Nature. 2014 Jun 12;510(7504):273-7
pubmed: 24776797
Sci Rep. 2016 Jan 08;6:19111
pubmed: 26743035
J Exp Med. 2006 Oct 2;203(10):2315-27
pubmed: 16954371
Science. 2010 Dec 3;330(6009):1349-54
pubmed: 21127246
Bioinformatics. 2009 Apr 15;25(8):1091-3
pubmed: 19237447
Circ Res. 2018 Mar 30;122(7):958-969
pubmed: 29343525
Angiogenesis. 2014 Oct;17(4):881-96
pubmed: 24903490
BMC Med Imaging. 2010 Jan 11;10:1
pubmed: 20064248
Circ Res. 2017 Sep 1;121(6):e22-e36
pubmed: 28743804
Cell Stem Cell. 2014 Jul 3;15(1):14-25
pubmed: 24996166
Nature. 2016 Oct 20;538(7625):388-391
pubmed: 27723741
J Mol Cell Cardiol. 2017 Nov;112:58-63
pubmed: 28823816
Proc Natl Acad Sci U S A. 2014 Nov 11;111(45):16029-34
pubmed: 25349429
Stem Cells. 2006 Jan;24(1):74-85
pubmed: 16099998
J Am Coll Cardiol. 2013 Nov 12;62(20):1890-901
pubmed: 23973704
Adv Drug Deliv Rev. 2017 Oct 1;120:2-24
pubmed: 29054357
Circ Res. 2015 Jun 19;117(1):80-8
pubmed: 26089365
Circ Res. 2001 Dec 7;89(12):1199-208
pubmed: 11739286
J Neuroimmunol. 2011 Apr;233(1-2):106-11
pubmed: 21354631
Elife. 2019 Mar 26;8:
pubmed: 30912746
EMBO Rep. 2017 Jul;18(7):1199-1212
pubmed: 28536247
Nat Biotechnol. 2017 Apr 11;35(4):291
pubmed: 28398319
J Mol Cell Cardiol. 2012 Sep;53(3):401-8
pubmed: 22728218
Nat Immunol. 2019 Jan;20(1):29-39
pubmed: 30538339
Nature. 2020 Jan;577(7790):405-409
pubmed: 31775156
Stem Cells. 2012 Jun;30(6):1196-205
pubmed: 22438013
Nat Biotechnol. 2007 Sep;25(9):1015-24
pubmed: 17721512
Immunity. 2014 Jan 16;40(1):91-104
pubmed: 24439267
Nat Biotechnol. 2004 Oct;22(10):1282-9
pubmed: 15448703
Sci Data. 2018 Jul 24;5:180145
pubmed: 30040082
J Am Coll Cardiol. 2007 Nov 6;50(19):1884-93
pubmed: 17980256
Cells. 2019 Dec 11;8(12):
pubmed: 31835854
Circulation. 2017 Mar 7;135(10):e146-e603
pubmed: 28122885
Nat Biotechnol. 2018 Aug;36(7):597-605
pubmed: 29969440