Human cord blood stem cells enhance neonatal right ventricular function in an ovine model of right ventricular training.
BACKGROUND
Nonischemic right ventricular dysfunction and cardiac failure is a source of considerable morbidity in children with congenital heart disease. Cell transplantation has not previously been studied in the pediatric setting in which enhancing ventricular function in response to supraphysiologic workloads might be beneficial.


METHODS
Engraftment and differentiation of human cord blood stem cells were studied in an immunosuppressed neonatal ovine model of right ventricular training. Week-old sheep underwent pulmonary artery banding and epicardial injection of cord blood stem cells (n=8) or pulmonary artery banding and placebo injection (n=8). Control groups received cord blood stem cells (n=6) or placebo (n=6) injection without pulmonary artery banding. Right ventricular function was measured at baseline and 1 month later using conductance catheter.


RESULTS
Cord blood stem cells were detected in the myocardium, spleen, kidney, and bone marrow up to 6 weeks after transplantation and expressed the hematopoietic markers CD45 and CD23. We identified neither differentiation nor fusion of transplanted human cells. In the groups undergoing pulmonary artery banding, cord blood stem cell transplantation was accompanied by functional benefits compared with placebo injection: end-systolic elastance increased by a mean of 1.4 +/- 0.2 mm Hg/mL compared with 0.9 +/- 0.1 mm Hg/mL, and the slope of preload recruitable stroke work increased by 21.1 +/- 2.9 mm Hg compared with 15.8 +/- 2.5 mm Hg. Cord blood stem cell transplantation had no significant effect on right ventricular function in the absence of pulmonary artery banding.


CONCLUSIONS
Our data demonstrate that in the presence of increased workload, cord blood stem cells engraft and augment right ventricular function. Transplanted cells adopt hematopoietic fates in the myocardium, bone marrow, and spleen.
Davies
Ben
B
Australia and New Zealand Children's Heart Research Centre, University of Melbourne, Melbourne, Australia. ben_davies@doctors.org.uk
Elwood
Ngaire J
NJ
Li
Shan
S
Cullinane
Fiona
F
Edwards
Glenn A
GA
Newgreen
Donald F
DF
Brizard
Christian P
CP
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D036101:Cord Blood Stem Cell Transplantation; D004195:Disease Models, Animal; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D006352:Heart Ventricles / Q000473:pathology; D006411:Hematopoiesis, Extramedullary / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D007231:Infant, Newborn; D007267:Injections; D017493:Leukocyte Common Antigens / Q000235:genetics; D018613:Microscopy, Confocal; D009200:Myocardial Contraction / Q000502:physiology; D010496:Pericardium; D011247:Pregnancy; D017455:Receptors, IgE / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D013599:Systole / Q000502:physiology; D018497:Ventricular Dysfunction, Right / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016278:Ventricular Function, Right / Q000502:physiology*
D005819:Genetic Markers; D017455:Receptors, IgE; D017493:Leukocyte Common Antigens