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).
Messina
Elisa
E
Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy.
De Angelis
Luciana
L
Frati
Giacomo
G
Morrone
Stefania
S
Chimenti
Stefano
S
Fiordaliso
Fabio
F
Salio
Monica
M
Battaglia
Massimo
M
Latronico
Michael V G
MV
Coletta
Marcello
M
Vivarelli
Elisabetta
E
Frati
Luigi
L
Cossu
Giulio
G
Giacomello
Alessandro
A
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*