Human cardiac progenitor cells with regenerative potential can be isolated and characterized from 3D-electro-anatomic guided endomyocardial biopsies.
OBJECTIVE
In the present study, we aimed to develop a percutaneous approach and a reproducible methodology for the isolation and expansion of Cardiac Progenitor Cells (CPCs) from EndoMyocardial Biopsies (EMB) in vivo. Moreover, in an animal model of non-ischemic heart failure (HF), we would like to test whether CPCs obtained by this methodology may engraft the myocardium and differentiate.


RESULTS
EMB were obtained using a preformed sheath and a disposable bioptome, advanced via right femoral vein in 12 healthy mini pigs, to the right ventricle. EMB were enzymatically dissociated, cells were expanded and sorted for c-kit. We used 3D-Electro-Anatomic Mapping (3D-EAM) to obtain CPCs from 32 patients affected by non-ischemic cardiomyopathy. The in vivo regenerative potential of CPCs was tested in a rodent model of drug-induced non-ischemic cardiomyopathy. c-kit positive CPCs replicative capacity was assessed in 30 patients. Telomere length averaged 7.4±0.4kbp and telomerase activity was present in all preparations (1.7×105copies). The in situ hybridization experiments showed that injected human CPCs may acquire a neonatal myocyte phenotype given the expression of the alpha-sarcomeric actin together with the presence of the Alu probe, suggesting a beneficial impact on LV performance.


CONCLUSIONS
The success in obtaining CPCs characterized by high regenerative potential, in vitro and in vivo, from EMB indicates that harvesting without thoracotomy in patients affected by either ischemic or non-ischemic cardiomyopathy is feasible. These initial results may potentially expand the future application of CPCs to all patients affected by HF not undergoing surgical procedures.
Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Rome, Italy. Electronic address: domenico.damario@gmail.com.
Domenico
D
D'Amario
Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Antonio Maria
AM
Leone
Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Maria Lucia
ML
Narducci
Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Costantino
C
Smaldone
Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Dalgisio
D
Lecis
Department of Pathology, Catholic University of the Sacred Heart, Rome, Italy.
Frediano
F
Inzani
Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Marco
M
Luciani
Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Andrea
A
Siracusano
Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Federica
F
La Neve
Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Melissa
M
Manchi
Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Gemma
G
Pelargonio
Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Francesco
F
Perna
Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Piergiorgio
P
Bruno
Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Massimo
M
Massetti
Institute of Internal Medicine and Diabetes Care Unit, Catholic University of the Sacred Heart, Rome, Italy.
Dario
D
Pitocco
Department of Experimental Medicine, Section of Pharmacology, Università della Campania "Luigi Vanvitelli", Naples, Italy.
Donato
D
Cappetta
Department of Experimental Medicine, Section of Pharmacology, Università della Campania "Luigi Vanvitelli", Naples, Italy.
Grazia
G
Esposito
Department of Experimental Medicine, Section of Pharmacology, Università della Campania "Luigi Vanvitelli", Naples, Italy.
Konrad
K
Urbanek
Department of Experimental Medicine, Section of Pharmacology, Università della Campania "Luigi Vanvitelli", Naples, Italy.
Antonella
A
De Angelis
Department of Experimental Medicine, Section of Pharmacology, Università della Campania "Luigi Vanvitelli", Naples, Italy.
Francesco
F
Rossi
Institute of Human Physiology, Catholic University of the Sacred Heart, Rome, Italy.
Roberto
R
Piacentini
Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Giulia
G
Angelini
Institute of Human Physiology, Catholic University of the Sacred Heart, Rome, Italy.
Domenica Donatella
DD
Li Puma
Institute of Human Physiology, Catholic University of the Sacred Heart, Rome, Italy; San Raffaele Pisana Scientific Institute for Research, Hospitalization and Health Care, Rome, Italy.
Claudio
C
Grassi
Laboratory of Molecular Biology, Institute of Biochemistry and Clinical Biochemistry, Catholic University of the Sacred Heart, Rome, Italy.
Elisa
E
De Paolis
Laboratory of Molecular Biology, Institute of Biochemistry and Clinical Biochemistry, Catholic University of the Sacred Heart, Rome, Italy.
Ettore
E
Capoluongo
Department of Radiological Sciences, Institute of Radiology, Catholic University of the Sacred Heart, Rome, Italy.
Valentina
V
Silvestri
Department of Radiological Sciences, Institute of Radiology, Catholic University of the Sacred Heart, Rome, Italy.
Biagio
B
Merlino
Department of Radiological Sciences, Institute of Radiology, Catholic University of the Sacred Heart, Rome, Italy.
Riccardo
R
Marano
Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Rome, Italy. Electronic address: Filippo.Crea@unicatt.it.
Filippo
F
Crea
D000328:Adult; D000818:Animals; D019560:Echocardiography, Three-Dimensional / Q000379:methods*; D004699:Endocardium / Q000166:cytology* / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000502:physiology* / Q000637:transplantation; D012038:Regeneration / Q000502:physiology; D013234:Stem Cells / Q000502:physiology*; D013552:Swine; D013556:Swine, Miniature
3D-endomyocardial biopsies; Cardiac progenitor/stem cells; Endomyocardial biopsies; Heart failure