Isolation and expansion of adult cardiac stem cells from human and murine heart.
Cardiac myocytes have been traditionally regarded as terminally differentiated cells that adapt to increased work and compensate for disease exclusively through hypertrophy. However, in the past few years, compelling evidence has accumulated suggesting that the heart has regenerative potential. Recent studies have even surmised the existence of resident cardiac stem cells, endothelial cells generating cardiomyocytes by cell contact or extracardiac progenitors for cardiomyocytes, but these findings are still controversial. We describe the isolation of undifferentiated cells that grow as self-adherent clusters (that we have termed "cardiospheres") from subcultures of postnatal atrial or ventricular human biopsy specimens and from murine hearts. These cells are clonogenic, express stem and endothelial progenitor cell antigens/markers, and appear to have the properties of adult cardiac stem cells. They are capable of long-term self-renewal and can differentiate in vitro and after ectopic (dorsal subcutaneous connective tissue) or orthotopic (myocardial infarction) transplantation in SCID beige mouse to yield the major specialized cell types of the heart: myocytes (ie, cells demonstrating contractile activity and/or showing cardiomyocyte markers) and vascular cells (ie, cells with endothelial or smooth muscle markers).
Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy.
Elisa
E
Messina
Luciana
L
De Angelis
Giacomo
G
Frati
Stefania
S
Morrone
Stefano
S
Chimenti
Fabio
F
Fiordaliso
Monica
M
Salio
Massimo
M
Battaglia
Michael V G
MV
Latronico
Marcello
M
Coletta
Elisabetta
E
Vivarelli
Luigi
L
Frati
Giulio
G
Cossu
Alessandro
A
Giacomello
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002449:Cell Aggregation; D002454:Cell Differentiation; D002455:Cell Division; D002469:Cell Separation / Q000379:methods*; D002478:Cells, Cultured / Q000166:cytology; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells / Q000166:cytology; D018920:Coculture Techniques; D005434:Flow Cytometry; D017930:Genes, Reporter; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D051379:Mice; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D008822:Mice, Transgenic; D008875:Middle Aged; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000628:therapy; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology*; D009940:Organoids / Q000166:cytology; D051381:Rats; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*