Therapeutic potential of extracellular vesicles derived from cardiac progenitor cells in rodent models of chemotherapy-induced cardiomyopathy.
Front Cardiovasc Med
; 10: 1206279, 2023.
Article
in En
| MEDLINE
| ID: mdl-37485274
ABSTRACT
Background:
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:
Immuno-competent mice received intra-peritoneal injections (IP) of doxorubicin (DOX) (4â mg/kg each; cumulative dose 12â 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 (3â mg/kg each; cumulative dose 15â mg/kg) followed by 3 equal IV injections of GMP-EV (total dose 100 billion). Cardiac function was assessed by two dimensional-echocardiography.Results:
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 (p = 0.043, p = 0.042, p = 0.048 respectively) while EV-CPC preserved these indices. Global longitudinal strain followed a similar pattern. In the rat model, IV injections of GMP-EV also preserved left ventricular end-systolic and end-diastolic volumes compared with untreated controls.Conclusions:
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Clinical_trials
Language:
En
Journal:
Front Cardiovasc Med
Year:
2023
Document type:
Article
Affiliation country:
France