Absence of Initial Cellular Immune Response in Children and Young Adults Receiving Decellularized Pulmonary Allografts

Objectives: Decellularized homografts (DH), which have shown promising early results in pulmonary valve replacement in children and young adults, could potentially avoid significant activation of the immune system, as more than 99% of donor DNA is removed during the decellularization process. The aim of this study was to evaluate whether implantation of a fresh decellularized human allograft induces a cellular immune response.

Methods: Peripheral blood samples were obtained from patients undergoing pulmonary valve replacement with DH before operation, directly postoperatively, after 3 and 6 months and then every 6 months up to 3 years after DH implantation. Absolute counts and percentages of mature T-(CD3), B-(CD19), and NK-(CD56) cells, as well as T helper-(CD4) and cytotoxic T cell (CD8) subsets, were determined by FACS analysis.

Results: Starting in May 2009, 144 blood samples from 47 patients (median [IQR] age: 14.0 [8.7 – 21.1] years, range: 0.5 month-51 years) were analyzed. Hemodynamic performance of DH was excellent. No valve-related deaths or conduit explantations were observed. Follow-up revealed a mild decrease in cell count of most subtypes postoperatively with reconstitution after 3 months, while long-term follow-up did not show any significant deviation of numbers of cell subsets.

Conclusion: The lack of immune response in patients receiving DH supports the concept of decellularization as the basis for autologous regeneration.