Background: Engineered tissue heart valves may become a promising therapeutics for heart valve disease. Compared with synthetic materials, acellular porcine scaffolds are considered as suitable matrices for tissue-engineered heart valves for the mechanical and structural properties of native tissue. Whether acellular porcine scaffolds can cause infection in recipients with porcine endogenous retrovirus (PERV) is critical for evaluating the safety of transplantation of tissue-engineered heart valves based on acellular porcine scaffolds. This study was completed to evaluate the risk of PERV transmission for application of acellular porcine aortic valves (PAVs).
Methods: Native aortic valves obtained from Chinese pigs of different species were acellularized by our modified detergent-enzymatic acellularization procedure. Polymerase chain reaction and reverse transcriptase polymerase chain reaction for pol sequences were used to detect PERV infection. In vitro, ovine endothelial cells (ECs) were inoculated and cocultured with supernatants of porcine aortic endothelial cells (PAECs) and acellualr PAVs, respectively. On 7th day, DNA and RNA of ovine ECs were isolated and tested for PERV. In vivo, acellular PAVs were implanted in the descending thoracic aorta in 40 sheep. Blood samples from the sheep and implanted acellular PAVs were collected 24 months after operation and tested for PERV.
Results: All cells were removed from the PAVs. Acellularized PAVs were repopulated by autologous cells of the host 24 months after implantation. PERV was detected in all native PAVs, porcine blood samples, acellularized PAVs and ovine ECs inoculated with supernatants of PAECs; no PERV was detected in ovine ECs cocultured with acellularized PAVs, ovine blood samples, and implanted acellular PAVs.
Conclusions: Acellularized PAVs processed by modified detergent-enzymatic acellularization procedure can be used for cardiovascular tissue-engineered grafts as matrix scaffolds without risk of PERV transmission.