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Updated: Jun 16, 2026
Chronic Ovine Model of Right Ventricular Failure and Functional Tricuspid Regurgitation
Published on: March 17, 2023
Human cord blood stem cells enhance neonatal right ventricular function in an ovine model of right ventricular
Ben Davies1, Ngaire J Elwood, Shan Li
1Australia and New Zealand Children's Heart Research Centre, University of Melbourne, Melbourne, Australia. ben_davies@doctors.org.uk
Insights
Human cord blood stem cells improved right ventricular function in a sheep model of heart failure. This study shows potential for cell therapy in pediatric congenital heart disease under increased workload.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Pediatric Cardiology
Background:
- Nonischemic right ventricular dysfunction is a significant issue in pediatric congenital heart disease.
- Cell transplantation has not been explored in pediatric settings for enhancing ventricular function under high workload.
Purpose of the Study:
- To investigate the engraftment and functional effects of human cord blood stem cells in a neonatal ovine model of right ventricular training.
- To determine if cord blood stem cells can improve ventricular function in response to increased workload.
Main Methods:
- Neonatal sheep underwent pulmonary artery banding to simulate increased workload.
- Epicardial injection of human cord blood stem cells or placebo was administered.
- Right ventricular function was assessed using conductance catheterization before and after intervention.
Main Results:
- Human cord blood stem cells were detected in various tissues up to 6 weeks post-transplantation, expressing hematopoietic markers.
- No differentiation or fusion of transplanted cells was observed.
- In the pulmonary artery banding group, stem cell transplantation significantly improved right ventricular function compared to placebo.
Conclusions:
- Cord blood stem cells engraft and enhance right ventricular function when the heart is under increased workload.
- Transplanted cells primarily adopt hematopoietic fates within the myocardium, bone marrow, and spleen.
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.
