Early Systemic Cellular Immune Response in Children and Young Adults Receiving Decellularized Fresh Allografts for Pulmonary Valve Replacement

• Published in: Tissue engineering. Part A 2014-03, Vol.20 (5-6), p.13-1011
• Main Authors: Neumann, Anneke, Sarikouch, Samir, Breymann, Thomas, Cebotari, Serghei, Boethig, Dietmar, Horke, Alexander, Beerbaum, Philipp, Westhoff-Bleck, Mechthild, Bertram, Harald, Ono, Masamichi, Tudorache, Igor, Haverich, Axel, Beutel, Gernot
• Format: Article
• Language: English
• Subjects: Adolescent; Allografts - immunology; Allografts - transplantation; Cellular biology; Child; Children & youth; Cohort Studies; Female; Follow-Up Studies; Hemodynamics; Humans; Immunity, Cellular - immunology; Male; Original; Original Articles; Pulmonary arteries; Pulmonary Valve - immunology; Pulmonary Valve - transplantation; Skin & tissue grafts; Young Adult; Young adults
• ISSN: 1937-3341; 1937-335X
• DOI: 10.1089/ten.tea.2013.0316

Objectives: The longevity of homografts is determined by the activation of the recipients' immune system resulting from allogenic antigen exposition. Fresh decellularized pulmonary homografts (DPH) have shown promising early results in pulmonary valve replacement in children and young adults and could potentially avoid significant activation of the immune system, as more than 99% of the donor DNA is removed during the decellularization process. While the humoral immune response to decellularized allografts has been studied, detailed information on the more significant cellular immune response is currently lacking. Methods and Results: Peripheral blood samples were obtained from patients undergoing pulmonary valve replacement with DPH before, after, and for approximately 3 years after implantation. Absolute counts and percentages of mature T- (CD3 + ), B- (CD19 + ), and natural killer- (CD16 + /CD56 + ) cells, as well as T helper- (CD4 + ) and cytotoxic T-cell- (CD8 + ) subsets, were determined by fluorescence-activated cell sorting (FACS). Between May 2009 and September 2013, 199 blood samples taken from 47 patients with a mean age at DPH implantation of 16.6±10.8 years were analyzed. The hemodynamic performance of DPH was excellent in all but one patient, and no valve-related deaths or conduit explantations were observed. The short-term follow up revealed a significant postoperative decrease in cell counts of most subtypes with reconstitution after 3 months. Continued assessment did not show any significant deviations in cell counts from their baseline values. Conclusion: The absence of cellular immune response in patients receiving DPH supports the concept that decellularization can provide a basis for autologous regeneration.