Decellularization reduces immunogenicity of sheep pulmonary artery vascular patches

J Thorac Cardiovasc Surg. 2011 Apr;141(4):1056-62. doi: 10.1016/j.jtcvs.2010.02.060. Epub 2010 Jul 15.

Abstract

Objectives: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / surgery
  • Bioprosthesis*
  • Blood Vessel Prosthesis Implantation / instrumentation*
  • Blood Vessel Prosthesis*
  • Calcinosis / etiology
  • Cryopreservation
  • Cytokines / genetics
  • Graft Rejection / immunology
  • Graft Rejection / pathology
  • Graft Rejection / prevention & control*
  • Graft Survival*
  • Immunity, Humoral*
  • Immunohistochemistry
  • Isoantibodies / blood
  • Microscopy, Electron, Scanning
  • Pulmonary Artery / immunology
  • Pulmonary Artery / pathology
  • Pulmonary Artery / transplantation*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sheep
  • Time Factors
  • Transplantation Tolerance*
  • Transplantation, Homologous

Substances

  • Cytokines
  • Isoantibodies
  • RNA, Messenger