Therapeutic potential of extracellular vesicles derived from cardiac progenitor cells in rodent models of chemotherapy-induced cardiomyopathy.
cardiac strain
cardio-oncology
cardiovascular progenitor
chemotherapy-induced cardiomyopathy
extracellular vesicles
regenerative medicine
Journal
Frontiers in cardiovascular medicine
ISSN: 2297-055X
Titre abrégé: Front Cardiovasc Med
Pays: Switzerland
ID NLM: 101653388
Informations de publication
Date de publication:
2023
2023
Historique:
received:
15
04
2023
accepted:
13
06
2023
medline:
24
7
2023
pubmed:
24
7
2023
entrez:
24
7
2023
Statut:
epublish
Résumé
Current treatments of chemotherapy-induced cardiomyopathy (CCM) are of limited efficacy. We assessed whether repeated intravenous injections of human extracellular vesicles from cardiac progenitor cells (EV-CPC) could represent a new therapeutic option and whether EV manufacturing according to a Good Manufacturing Practices (GMP)-compatible process did not impair their bioactivity. Immuno-competent mice received intra-peritoneal injections (IP) of doxorubicin (DOX) (4 mg/kg each; cumulative dose: 12 mg/kg) and were then intravenously (IV) injected three times with EV-CPC (total dose: 30 billion). Cardiac function was assessed 9-11 weeks later by cardiac magnetic resonance imaging (CMR) using strain as the primary end point. Then, immuno-competent rats received 5 IP injections of DOX (3 mg/kg each; cumulative dose 15 mg/kg) followed by 3 equal IV injections of GMP-EV (total dose: 100 billion). Cardiac function was assessed by two dimensional-echocardiography. In the chronic mouse model of CCM, DOX + placebo-injected hearts incurred a significant decline in basal (global, epi- and endocardial) circumferential strain compared with sham DOX-untreated mice ( Intravenously-injected extracellular vesicles derived from CPC have cardio-protective effects which may make them an attractive user-friendly option for the treatment of CCM.
Sections du résumé
Background
UNASSIGNED
Current treatments of chemotherapy-induced cardiomyopathy (CCM) are of limited efficacy. We assessed whether repeated intravenous injections of human extracellular vesicles from cardiac progenitor cells (EV-CPC) could represent a new therapeutic option and whether EV manufacturing according to a Good Manufacturing Practices (GMP)-compatible process did not impair their bioactivity.
Methods
UNASSIGNED
Immuno-competent mice received intra-peritoneal injections (IP) of doxorubicin (DOX) (4 mg/kg each; cumulative dose: 12 mg/kg) and were then intravenously (IV) injected three times with EV-CPC (total dose: 30 billion). Cardiac function was assessed 9-11 weeks later by cardiac magnetic resonance imaging (CMR) using strain as the primary end point. Then, immuno-competent rats received 5 IP injections of DOX (3 mg/kg each; cumulative dose 15 mg/kg) followed by 3 equal IV injections of GMP-EV (total dose: 100 billion). Cardiac function was assessed by two dimensional-echocardiography.
Results
UNASSIGNED
In the chronic mouse model of CCM, DOX + placebo-injected hearts incurred a significant decline in basal (global, epi- and endocardial) circumferential strain compared with sham DOX-untreated mice (
Conclusions
UNASSIGNED
Intravenously-injected extracellular vesicles derived from CPC have cardio-protective effects which may make them an attractive user-friendly option for the treatment of CCM.
Identifiants
pubmed: 37485274
doi: 10.3389/fcvm.2023.1206279
pmc: PMC10360184
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1206279Informations de copyright
© 2023 Desgres, Lima Correa, Petrusca, Autret, Pezzana, Marigny, Guillas, Bellamy, Vilar, Perier, Dingli, Loew, Humbert, Larghero, Churlaud, Renault, Croisille, Hagège, Silvestre and Menasché.
Déclaration de conflit d'intérêts
NR is a full time employee of FUJIFILM Cellular Dynamics, Inc. PM is a member of the Strategic Advisory Board of FUJIFILM Cellular Dynamics, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The remaining 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
Circ Res. 2017 Jan 20;120(2):332-340
pubmed: 27856497
J Extracell Vesicles. 2015 Apr 20;4:26316
pubmed: 25899407
J Am Heart Assoc. 2014 Jan 13;3(1):e000550
pubmed: 24419736
Nat Rev Neurol. 2023 Jan;19(1):9-18
pubmed: 36396913
Arterioscler Thromb Vasc Biol. 2021 Nov;41(11):2648-2660
pubmed: 34587760
Nat Rev Cardiol. 2020 Nov;17(11):685-697
pubmed: 32483304
Circ Res. 2017 Oct 27;121(10):1192-1204
pubmed: 28974553
Echocardiography. 2018 Jul;35(7):922-934
pubmed: 29603386
Front Pharmacol. 2022 Nov 24;13:1052091
pubmed: 36506565
Eur Heart J Suppl. 2021 Oct 08;23(Suppl E):E28-E32
pubmed: 35233212
Sci Rep. 2019 Mar 15;9(1):4647
pubmed: 30874584
J Am Coll Cardiol. 2012 Mar 6;59(10):942-53
pubmed: 22381431
J Am Heart Assoc. 2018 Feb 13;7(4):
pubmed: 29440036
Biochem Biophys Res Commun. 2018 Sep 18;503(4):2611-2618
pubmed: 30126637
J Am Coll Cardiol. 2009 Aug 11;54(7):618-24
pubmed: 19660692
Eur Heart J. 2018 May 21;39(20):1835-1847
pubmed: 29420830
Am J Respir Crit Care Med. 2018 Jan 1;197(1):104-116
pubmed: 28853608
Cardiovasc Res. 2020 Feb 1;116(2):383-392
pubmed: 31098627
Nat Commun. 2020 Feb 28;11(1):1064
pubmed: 32111836
Cell Transplant. 2012;21(9):1919-30
pubmed: 22449713
Aging (Albany NY). 2019 Feb 21;11(4):1129-1150
pubmed: 30792374
Transl Stroke Res. 2018 Oct;9(5):530-539
pubmed: 29285679
Eur Heart J. 2022 Jul 14;43(27):2562-2569
pubmed: 34951629
Eur Heart J. 2016 Sep 21;37(36):2768-2801
pubmed: 27567406
Circulation. 2018 Aug 14;138(7):696-711
pubmed: 29348263
J Basic Clin Pharm. 2016 Mar;7(2):27-31
pubmed: 27057123
Eur J Heart Fail. 2020 Sep;22(9):1504-1524
pubmed: 32621569
JACC CardioOncol. 2020 Nov;2(4):581-595
pubmed: 33403362
Nucl Med Biol. 2022 Sep-Oct;112-113:20-30
pubmed: 35763877
Stem Cell Res Ther. 2022 Jun 17;13(1):253
pubmed: 35715868
Commun Biol. 2022 Jul 28;5(1):753
pubmed: 35902687
Heart Fail Rev. 2021 Jul;26(4):881-890
pubmed: 33319255
Hum Exp Toxicol. 2019 Jul;38(7):857-874
pubmed: 30991846
Circ Heart Fail. 2015 Jan;8(1):98-108
pubmed: 25420486
Sci Rep. 2016 Jul 21;6:29994
pubmed: 27444332
J Heart Lung Transplant. 2016 Nov;35(11):1348-1357
pubmed: 27342903
J Am Soc Echocardiogr. 2014 Sep;27(9):911-39
pubmed: 25172399
Cardiovasc Res. 2021 Jan 1;117(1):292-307
pubmed: 32049348
J Extracell Vesicles. 2018 Nov 23;7(1):1535750
pubmed: 30637094
JAMA. 1991 Sep 25;266(12):1672-7
pubmed: 1886191
Front Physiol. 2021 Apr 07;12:658790
pubmed: 33897465
G3 (Bethesda). 2019 Aug 8;9(8):2637-2646
pubmed: 31263061
Sci Rep. 2021 Apr 21;11(1):8666
pubmed: 33883598
Circ Res. 2018 Jul 6;123(2):138-158
pubmed: 29976684
Sci Rep. 2018 Jan 25;8(1):1579
pubmed: 29371689
Circ Res. 2017 Mar 3;120(5):816-834
pubmed: 27908912
JACC CardioOncol. 2021 Jul 27;3(3):428-440
pubmed: 34604804
Circ Res. 2020 Mar 27;126(7):926-941
pubmed: 32213135