Ex-vivo expanded umbilical cord blood stem cells retain capacity for myocardial regeneration.
BACKGROUND
Umbilical cord blood (UCB) is a source of human hematopoietic precursor cells (HPCs), a stem cell (SC) type that has been used in several trials for myocardial repair. A certain minimal number of cells is required for measurable regeneration and a major challenge of SC-based regenerative therapy constitutes ex-vivo expansion of the primitive cell compartment. The aim of this study was to investigate the ex-vivo expansion potential of UCB-derived HPCs and the ability of these expanded cells to migrate to the site of damage and improve ventricular function in a rodent model of myocardial infarction (MI).


RESULTS
UCB-derived HPCs, defined by coexpression of CD133 and CD34, were expanded using various cytokine combinations. MI was induced by left anterior descending artery ligation in nude rats. Cells were injected intravenously 2 days after infarction. The combination of SC factor, thrombopoietin, flt3-ligand and interleukin-6 was found to be the most effective for inducing proliferation of HPCs. The migratory capacity of expanded HPCs was similar to that of non-expanded HPCs and improvement of ejection fraction was significant in both groups, with a relative increase of >60%.


CONCLUSIONS
UCB-derived HPCs can be reproducibly expanded ex-vivo and retain their potential to improve cardiac function post-MI. (Circ J 2010; 74: 188 - 194).
Schlechta
Bernhard
B
University Clinic of Cardiac Surgery, Medical University of Innsbruck, Austria. bernhard.schlechta@meduniwien.ac.at
Wiedemann
Dominik
D
Kittinger
Clemens
C
Jandrositz
Anita
A
Bonaros
Nikolaos E
NE
Huber
Johannes C
JC
Preisegger
Karl-Heinz
KH
Kocher
Alfred A
AA
D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation; D003331:Coronary Vessels / Q000503:physiopathology; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007378:Interleukins / Q000494:pharmacology; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012038:Regeneration / Q000502:physiology*
D007378:Interleukins