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A Novel Model for Xenograft Right Ventricle to Pulmonary Artery Conduit
Chace B Mitchell1, Luke M Wiggins, Winfield J Wells
1From the Division of Cardiothoracic Surgery, Department of Surgery, Heart Institute, Children's Hospital of Los Angeles, University of Southern California, Los Angeles, California.
Insights
Genetically engineered porcine conduits show promise for growing pediatric heart valve replacements. This innovative xenograft approach in nonhuman primates offers a potential solution for right ventricular to pulmonary artery discontinuity, needing further long-term study.
Area of Science:
- Biomedical Engineering
- Cardiovascular Surgery
- Regenerative Medicine
Background:
- Neonatal cardiac surgery outcomes have improved significantly over 40 years.
- Long-term management of congenital heart disease survivors, especially pediatric heart valve disease, requires focus.
- Current valved conduit options for right ventricular to pulmonary artery (RVPA) discontinuity are limited by patient size and growth potential.
Purpose of the Study:
- To evaluate the feasibility of using genetically engineered porcine (GEP) donor RVPA conduits in infantile nonhuman primate (NHP) recipients.
- To assess the short-term efficacy and safety of GEP conduits under single-drug immunosuppression.
Main Methods:
- Development of a preclinical model using GEP donor RVPA conduits in infantile NHP recipients.
- Administration of single-drug immunosuppression to NHP recipients.
- Short-term follow-up to assess for pulmonary valve insufficiency or stenosis.
Main Results:
- Successful placement of GEP donor RVPA conduits in infantile NHP recipients.
- NHP recipients maintained on single-drug immunosuppression showed no evidence of pulmonary valve insufficiency or stenosis during short-term follow-up.
Conclusions:
- Genetically engineered porcine RVPA conduits represent a potential xenograft alternative for pediatric heart valve replacement.
- This preclinical model demonstrates short-term feasibility and safety, warranting further investigation into long-term outcomes and human application.
Abstract:
The last 40 years have shown dramatic improvement in outcomes for neonatal cardiac surgery for a spectrum of congenital heart disease diagnoses. With more patients surviving into adulthood, the long-term impact of initial management strategies of these patients has come into focus. This is particularly true for patients with pediatric heart valve disease. Many patients born with right ventricular to pulmonary artery (RVPA) discontinuity require placement of a valved conduit in the neonatal period. Valved conduit options are limited in this patient population due to patient size and inability to respond to somatic growth. Genetically engineered porcine (GEP) donors may offer a xenograft conduit alternative that can grow with the patient. We have developed a model utilizing GEP donor RVPA conduits placed in infantile nonhuman primate (NHP) recipients. Our recipient is maintained on single-drug immunosuppression and demonstrates no evidence of pulmonary valve insufficiency or stenosis during short-term follow-up. Further studies and long-term outcomes are necessary to determine the utility of this technology in human application.
