Exosomal Expression of CXCR4 Targets Cardioprotective Vesicles to Myocardial Infarction and Improves Outcome after Systemic Administration

Autor: Giuseppe Vassalli, Giovanni G. Camici, Sara Bolis, Elisabetta Cervio, Giuseppina Milano, Vanessa Biemmi, A. Ciullo, Tiziano Moccetti, Emanuel T. Fertig, Lucio Barile, Mihaela Gherghiceanu
Přispěvatelé: University of Zurich, Barile, Lucio
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Benzylamines
Myocardial Infarction
1607 Spectroscopy
Fluorescent Antibody Technique
Pharmacology
Cyclams
Cell therapy
lcsh:Chemistry
0302 clinical medicine
Heterocyclic Compounds
intravenous injection
Myocardial infarction
lcsh:QH301-705.5
Spectroscopy
Cells
Cultured
Ejection fraction
General Medicine
Flow Cytometry
3. Good health
Computer Science Applications
030220 oncology & carcinogenesis
10209 Clinic for Cardiology
Systemic administration
1606 Physical and Theoretical Chemistry
Cardiac function curve
Receptors
CXCR4
1503 Catalysis
Cell Survival
Blotting
Western
Ischemia
cardiac progenitor cells
610 Medicine & health
Enzyme-Linked Immunosorbent Assay
macromolecular substances
exosomes
11171 Cardiocentro Ticino
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Animals
Cell Survival/drug effects
Cell Survival/genetics
Cell Survival/physiology
Chemokine CXCL12/genetics
Chemokine CXCL12/metabolism
Cryoelectron Microscopy
Exosomes/metabolism
Heterocyclic Compounds/therapeutic use
Humans
Myocardial Infarction/genetics
Myocardial Infarction/metabolism
Myocardial Infarction/therapy
RNA
Messenger/genetics
RNA
Messenger/metabolism
Rats
Rats
Wistar
Receptors
CXCR4/antagonists & inhibitors
Receptors
CXCR4/genetics
Receptors
CXCR4/metabolism
CXCR4
1312 Molecular Biology
1706 Computer Science Applications
medicine
RNA
Messenger
Physical and Theoretical Chemistry
Progenitor cell
Molecular Biology
1604 Inorganic Chemistry
business.industry
Organic Chemistry
fungi
medicine.disease
Chemokine CXCL12
carbohydrates (lipids)
enzymes and coenzymes (carbohydrates)
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
business
Reperfusion injury
1605 Organic Chemistry
Zdroj: International Journal of Molecular Sciences, Vol 20, Iss 3, p 468 (2019)
International Journal of Molecular Sciences
Volume 20
Issue 3
International journal of molecular sciences, vol. 20, no. 3
ISSN: 1422-0067
Popis: Cell therapy has been evaluated to enhance heart function after injury. Delivered cells mostly act via paracrine mechanisms, including secreted growth factors, cytokines, and vesicles, such as exosomes (Exo). Intramyocardial injection of cardiac-resident progenitor cells (CPC)-derived Exo reduced scarring and improved cardiac function after myocardial infarction in rats. Here, we explore a clinically relevant approach to enhance the homing process to cardiomyocytes (CM), which is crucial for therapeutic efficacy upon systemic delivery of Exo. By overexpressing exosomal CXCR4, we increased the efficacy of plasmatic injection of cardioprotective Exo-CPC by increasing their bioavailability to ischemic hearts. Intravenous injection of ExoCXCR4 significantly reduced infarct size and improved left ventricle ejection fraction at 4 weeks compared to ExoCTRL (p <
0.01). Hemodynamic measurements showed that ExoCXCR4 improved dp/dt min, as compared to ExoCTRL and PBS group. In vitro, ExoCXCR4 was more bioactive than ExoCTRL in preventing CM death. This in vitro effect was independent from SDF-1α, as shown by using AMD3100 as specific CXCR4 antagonist. We showed, for the first time, that systemic administration of Exo derived from CXCR4-overexpressing CPC improves heart function in a rat model of ischemia reperfusion injury These data represent a substantial step toward clinical application of Exo-based therapeutics in cardiovascular disease.
Databáze: OpenAIRE
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