Patient characteristics and cell source determine the number of isolated human cardiac progenitor cells.
BACKGROUND
The identification and isolation of human cardiac progenitor cells (hCPCs) offer new approaches for myocardial regeneration and repair. Still, the optimal source of human cardiac progenitor cells and the influence of patient characteristics on their number remain unclear. Using a novel method to isolate human cardiac progenitor cells, we aimed to define the optimal source and association between their number and patient characteristics.


RESULTS
We developed a novel isolation method that produced viable cells (7 x 10(6)+/-6.53 x 10(5)/g) from various tissue samples obtained during heart surgery or endomyocardial biopsies (113 samples from 94 patients 23 to 80 years of age). The isolated cardiac cells were grown in culture with a stem cell expansion medium. According to fluorescence-activated cell sorting analysis, cultured cells derived from the right atrium generated higher amounts of c-kit(+) (24+/-2.5%) and Islet-1(+) cells (7%) in culture (mean of passages 1, 2, and 3) than did cultured cells from the left atrium (7.3+/-3.5%), right ventricle (4.1+/-1.6%), and left ventricle (9.7+/-3%; P=0.001). According to multivariable analysis, the right atrium as the cell source and female sex were associated with a higher number of c-kit(+) cells. There was no overlap between c-kit(+) and Islet-1 expression. In vitro assays of differentiation into osteoblasts, adipocytes, and myogenic lineage showed that the isolated human cardiac progenitor cells were multipotent. Finally, the cells were transplanted into infarcted myocardium of rats and generated myocardial grafts.


CONCLUSIONS
Our results show that the right atrium is the best source for c-kit(+) and Islet-1 progenitors, with higher percentages of c-kit(+) cells being produced by women.
Itzhaki-Alfia
Ayelet
A
Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Hashomer, Israel.
Leor
Jonathan
J
Raanani
Ehud
E
Sternik
Leonid
L
Spiegelstein
Dan
D
Netser
Shiri
S
Holbova
Radka
R
Pevsner-Fischer
Meirav
M
Lavee
Jacob
J
Barbash
Israel M
IM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001706:Biopsy; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006321:Heart / Q000502:physiology; D006325:Heart Atria / Q000166:cytology* / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D060850:LIM-Homeodomain Proteins; D008297:Male; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D051381:Rats; D011923:Rats, Nude; D012038:Regeneration / Q000502:physiology; D012727:Sex Characteristics; D033581:Stem Cell Transplantation; D014157:Transcription Factors
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D019009:Proto-Oncogene Proteins c-kit