Decellularization reduces immunogenicity of sheep pulmonary artery vascular patches.
OBJECTIVE
Allograft vascular tissue is important in the repair of complex structural lesions of the heart and great vessels, but induces a deleterious immune response that might shorten the effective lifespan of the tissue and sensitize the recipient. We hypothesized that decellularizing allograft vascular tissue reduces the host allogeneic immune response.


METHODS
Allograft ovine pulmonary artery patches were decellularized, cryopreserved, and implanted into the descending thoracic aorta. The humoral immune response was measured by means of flow cytometry at regular intervals over 6 months. Graft histology, immunohistochemistry, and calcification were assessed after 4 weeks or 6 months.


RESULTS
Leukocyte infiltration was reduced in decellularized grafts. A trend toward decreased in-patch calcification was observed in the decellularized group (7.6 ± 4.3 vs 40.0 ± 15.9 mg of calcium/mg of protein, P = .107). Decellularization reduced IgG antibody binding to donor splenocytes (9.8% ± 3.3% vs 57.8% ± 13.7% [control value], P = .010), as assessed by means of flow cytometry. All cytokines examined were detected in nondecellularized tissues after 4 weeks but not at 6 months, indicating complete graft rejection at that time. In contrast, transforming growth factor β1 and interleukin 10 were the only prominent cytokines in all decellularized grafts at 4 weeks after transplantation.


CONCLUSIONS
Decellularization of allograft vascular tissue minimized the recipient cellular immune response and eliminated the production of anti-donor antibodies in recipients.
Lehr
Eric J
EJ
Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA. elehr@smail.umaryland.edu
Rayat
Gina R
GR
Chiu
Brian
B
Churchill
Thomas
T
McGann
Locksley E
LE
Coe
James Y
JY
Ross
David B
DB
D000818:Animals; D001013:Aorta, Thoracic / Q000601:surgery; D001705:Bioprosthesis; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation / Q000295:instrumentation*; D002114:Calcinosis / Q000209:etiology; D015925:Cryopreservation; D016207:Cytokines / Q000235:genetics; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival; D056724:Immunity, Humoral; D007150:Immunohistochemistry; D007518:Isoantibodies / Q000097:blood; D008855:Microscopy, Electron, Scanning; D011651:Pulmonary Artery / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D013997:Time Factors; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous
D016207:Cytokines; D007518:Isoantibodies; D012333:RNA, Messenger