Endothelial-like cells expanded from CD34+ blood cells improve left ventricular function after experimental myocardial infarction.
Mobilization and recruitment of endothelial progenitor cells (EPC) contributes to vasculogenesis in vivo. So far, applications for cell therapy are limited by the number of available cells. Expansion of EPC or their progeny may, therefore, facilitate its therapeutic use in ischemic disease. The aim of this study was to expand CD34+ EPC-derived progeny from different sources, characterize them, and investigate their potential for use in therapeutic vasculogenesis. CD34+ cells from G-CSF-mobilized peripheral blood (PB) and cord blood (CB) were isolated using immunomagnetic beads and cultured in endothelial cell medium. Cells were expanded up to 16 (PB) and up to 46 (CB) population doublings, respectively. Immunophenotypic and mRNA expression analyses showed a high degree of similarity between the cultured cells and human umbilical vein endothelial cells (HUVEC). By day 14 after transplantation, transplanted human CD31-positive EPC-derived cells were detected. These cells expressed the proliferation marker Ki67 and formed vessel-like structures in ischemic myocardium. Most strikingly, transplantation of EPC-derived cells improved left ventricular function after experimental ischemia, as shown by echocardiography. In conclusion, cells cultured from CD34+ EPC can be expanded in vitro to clinically relevant numbers. In vivo, these cells proliferate, form vascular structures, and improve left ventricular function after experimental myocardial infarction. Therefore, in vitro expanded EPC-derived endothelial cells may be beneficial in the treatment of ischemic disease.
Ott
Ilka
I
I.Department of Medicine, Technical University Munich, Munich, Germany.
Keller
Ulrich
U
Knoedler
Martina
M
Götze
Katharina S
KS
Doss
Katharina
K
Fischer
Philipp
P
Urlbauer
Katja
K
Debus
Gerlinde
G
von Bubnoff
Nikolas
N
Rudelius
Martina
M
Schömig
Albert
A
Peschel
Christian
C
Oostendorp
Robert A J
RA
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis*; D001773:Blood Cells / Q000166:cytology*; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D005312:Fetal Blood / Q000166:cytology; D020869:Gene Expression Profiling; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D018189:Immunomagnetic Separation; D016130:Immunophenotyping; D008297:Male; D009203:Myocardial Infarction / Q000601:surgery; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000601:surgery; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011923:Rats, Nude; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology; D016277:Ventricular Function, Left
D018952:Antigens, CD34; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor