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J Thorac Cardiovasc Surg 2005;130:469-476
© 2005 The American Association for Thoracic Surgery

Evolving Technology

Decellularization reduces the immune response to aortic valve allografts in the rat

^a Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
^b Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
^c Faculty of Science, University of Alberta, Edmonton, Alberta, Canada.

Received for publication December 24, 2004; revisions received February 18, 2005; accepted for publication March 22, 2005.

^_* Address for reprints: Steven R. Meyer, MD, Department of Surgery, 2D4.37 Walter Mackenzie Health Sciences Centre, 8440-112 St, Edmonton, Alberta, Canada T6G 2B7. (Email: srmeyer{at}ualberta.ca).

OBJECTIVES: Cryopreserved valve allografts used in congenital cardiac surgery are associated with a significant cellular and humoral immune response. This might be reduced by removal of antigenic cellular elements (decellularization). The aim of this study was to determine the immunologic effect of decellularization in a rat allograft valve model.

METHODS: Brown Norway and Lewis rat aortic valves were decellularized with a series of hypotonic and hypertonic buffers, protease inhibitors, gentle detergents (Triton X-100), and phosphate-buffered saline. Valves were implanted into Lewis rats in syngeneic and allogeneic combinations. Cellular (CD3 and CD8) infiltrates were assessed with morphometric analysis, and the humoral response was assessed with flow cytometry.

RESULTS: Morphometric analysis identified a significant reduction in CD3⁺ cell infiltrates (cells per square millimeter of leaflet tissue) in decellularized allografts compared with that seen in nondecellularized allografts at 1 (79 ± 29 vs 3310 ± 223, P < .001), 2 (26 ± 11 vs 109 ± 20, P = .004), and 4 weeks (283 ± 122 vs 984 ± 145, P < .001). Anti-CD8 staining confirmed the majority of infiltrates were cytotoxic T cells. Flow cytometric mean channel fluorescence intensity identified a negative shift (abrogated antibody formation) for decellularized allografts compared with nondecellularized allografts at 2 (19 ± 1 vs 27 ± 3, P = .033), 4 (35 ± 2 vs 133 ± 29, P = .001), and 16 weeks (28 ± 2 vs 166 ± 54, P = .017).

CONCLUSIONS: Decellularization significantly reduces the cellular and humoral immune response to allograft tissue. This could prolong the durability of valve allografts and might prevent immunologic sensitization of allograft recipients.

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