Xenoantigenicity of porcine decellularized valves
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RESEARCH ARTICLE
Open Access
Xenoantigenicity of porcine decellularized valves Meghana R. K. Helder1, Nicholas J. Stoyles2, Brandon J. Tefft2, Ryan S. Hennessy2, Rebecca R. C. Hennessy2, Roy Dyer3, Tyra Witt2, Robert D. Simari2 and Amir Lerman2*
Abstract Background: The xenoantigenicity of porcine bioprosthetic valves is implicated as an etiology leading to calcification and subsequent valve failure. Decellularization of porcine valves theoretically could erase the antigenicity of the tissue leading to more durable prosthetic valves, but the effectiveness of decellularization protocols in regard to completely removing antigens has yet to be verified. Our hypothesis was that decellularization would remove the more abundant α-gal antigens but not remove all the non α-gal antigens, which could mount a response. Methods: Porcine aortic valves were decellularized with 1% sodium dodecyl sulfate for 4 days. Decellularized cusps were evaluated for α-gal epitopes by ELISA. To test for non α-gal antigens, valves were implanted into sheep. Serum was obtained from the sheep preoperatively and 1 week, 1 month, and 2 months postoperatively. This serum was utilized for anti-porcine antibody staining and for quantification of anti-pig IgM and IgG antibodies and complement. Results: Decellularized porcine cusps had 2.8 ± 2.0% relative α-gal epitope as compared to fresh porcine aortic valve cusps and was not statistically significantly different (p = 0.4) from the human aortic valve cusp which had a 2.0 ± 0.4% relative concentration. Anti-pig IgM and IgG increased postoperatively from baseline levels. Preoperatively anti-pig IgM was 27.7 ± 1.7 μg/mL and it increased to 71.9 ± 12.1 μg/mL average of all time points postoperatively (p = 0.04). Preoperatively anti-pig IgG in sheep serum was 44.9 ± 1.5 μg/mL and it increased to 72.6 ± 6.0 μg/mL average of all time points postoperatively (p = 0.01). There was a statistically significant difference (p = 0.00007) in the serum C1q concentration before valve implantation (2.5 ± 0.2 IU/mL) and at averaged time points after valve implantation (5.3 ± 0. 3 IU/mL). Conclusions: Decellularization with 1% sodium dodecyl sulfate does not fully eliminate non α-gal antigens; however, significant reduction in α-gal presence on decellularized cusps was observed. Clinical implications of the non α-gal antigenic response are yet to be determined. As such, evaluation of any novel decellularized xenografts must include rigorous antigen testing prior to human trials. Keywords: Valve deterioration, Valve durability, Immune response
Background The scarcity of aortic valve allografts has led to a large amount of research utilizing porcine aortic valves as a valve replacement option [1]. Commercial porcine bioprosthetic valves are widely used and are arguably a hemodynamically superior option for aortic valve replacement as compared to mechanical valves, and avoid * Correspondence: [email protected] This project has been presented at the American Association of Thoracic Surgeons on April 28, 2015 in Seattl
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