Safety and feasibility for pediatric cardiac regeneration using epicardial delivery of autologous umbilical cord blood-derived mononuclear cells established in a porcine model system

Susana Cantero Peral, Harold M. Burkhart, Saji Oommen, Satsuki Yamada, Scott Nyberg, Xing Li, Patrick W. O’Leary, Andre Terzic, Bryan C. Cannon, Timothy J Nelson

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Congenital heart diseases (CHDs) requiring surgical palliation mandate new treatment strategies to optimize long-term outcomes. Despite the mounting evidence of cardiac regeneration, there are no long-term safety studies of autologous cell-based transplantation in the pediatric setting. We aimed to establish a porcine pipeline to evaluate the feasibility and long-term safety of autologous umbilical cord blood mononuclear cells (UCB-MNCs) transplanted into the right ventricle (RV) of juvenile porcine hearts. Piglets were born by caesarean section to enable UCB collection. Upon meeting release criteria, 12 animals were randomized in a double-blinded fashion prior to surgical delivery of test article (n = 6) or placebo (n = 6). The UCB-MNC (3×106 cells per kilogram) or control (dimethyl sulfoxide, 10%) products were injected intramyocardially into the RV under direct visualization. The cohorts were monitored for 3 months after product delivery with assessments of cardiac performance, rhythm, and serial cardiac biochemical markers, followed by terminal necropsy. No mortalities were associated with intramyocardial delivery of UCB-MNCs or placebo. Two animals from the placebo group developed local skin infection after surgery that responded to antibiotic treatment. Electrophysiological assessments revealed no arrhythmias in either group throughout the 3-month study. Two animals in the cell-therapy group had transient, subclinical dysrhythmia in the perioperative period, likely because of an exaggerated response to anesthesia. Overall, this study demonstrated that autologous UCB-MNCs can be safely collected and surgically delivered in a pediatric setting. The safety profile establishes the foundation for cell-based therapy directed at the RV of juvenile hearts and aims to accelerate cell-based therapies toward clinical trials for CHD.

Original languageEnglish (US)
Pages (from-to)195-206
Number of pages12
JournalStem cells translational medicine
Volume4
Issue number2
DOIs
StatePublished - Jan 1 2015

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Keywords

  • Autologous umbilical cord blood
  • Congenital heart disease
  • Intramyocardial delivery
  • Porcine
  • Right ventricle
  • Safety

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology

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