Xenoantigenicity of porcine decellularized valves

Meghana R.K. Helder, Nicholas J. Stoyles, Brandon J. Tefft, Ryan S. Hennessy, Rebecca R.C. Hennessy, Roy Dyer, Tyra Witt, Robert D. Simari, Amir Lerman

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Article number56
JournalJournal of Cardiothoracic Surgery
Volume12
Issue number1
DOIs
StatePublished - Jul 17 2017

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Swine
Antigens
Aortic Valve
Sheep
Serum
Sodium Dodecyl Sulfate
Epitopes
Heterografts
Anti-Idiotypic Antibodies
Enzyme-Linked Immunosorbent Assay
Staining and Labeling
Antibodies
anti-IgG
anti-IgM

Keywords

  • Immune response
  • Valve deterioration
  • Valve durability

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

Cite this

Helder, M. R. K., Stoyles, N. J., Tefft, B. J., Hennessy, R. S., Hennessy, R. R. C., Dyer, R., ... Lerman, A. (2017). Xenoantigenicity of porcine decellularized valves. Journal of Cardiothoracic Surgery, 12(1), [56]. https://doi.org/10.1186/s13019-017-0621-5

Xenoantigenicity of porcine decellularized valves. / Helder, Meghana R.K.; Stoyles, Nicholas J.; Tefft, Brandon J.; Hennessy, Ryan S.; Hennessy, Rebecca R.C.; Dyer, Roy; Witt, Tyra; Simari, Robert D.; Lerman, Amir.

In: Journal of Cardiothoracic Surgery, Vol. 12, No. 1, 56, 17.07.2017.

Research output: Contribution to journalArticle

Helder, MRK, Stoyles, NJ, Tefft, BJ, Hennessy, RS, Hennessy, RRC, Dyer, R, Witt, T, Simari, RD & Lerman, A 2017, 'Xenoantigenicity of porcine decellularized valves', Journal of Cardiothoracic Surgery, vol. 12, no. 1, 56. https://doi.org/10.1186/s13019-017-0621-5
Helder MRK, Stoyles NJ, Tefft BJ, Hennessy RS, Hennessy RRC, Dyer R et al. Xenoantigenicity of porcine decellularized valves. Journal of Cardiothoracic Surgery. 2017 Jul 17;12(1). 56. https://doi.org/10.1186/s13019-017-0621-5
Helder, Meghana R.K. ; Stoyles, Nicholas J. ; Tefft, Brandon J. ; Hennessy, Ryan S. ; Hennessy, Rebecca R.C. ; Dyer, Roy ; Witt, Tyra ; Simari, Robert D. ; Lerman, Amir. / Xenoantigenicity of porcine decellularized valves. In: Journal of Cardiothoracic Surgery. 2017 ; Vol. 12, No. 1.
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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.",
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AU - Helder, Meghana R.K.

AU - Stoyles, Nicholas J.

AU - Tefft, Brandon J.

AU - Hennessy, Ryan S.

AU - Hennessy, Rebecca R.C.

AU - Dyer, Roy

AU - Witt, Tyra

AU - Simari, Robert D.

AU - Lerman, Amir

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N2 - 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.

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KW - Immune response

KW - Valve deterioration

KW - Valve durability

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