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2017 ; 12
(1
): 56
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Xenoantigenicity of porcine decellularized valves
#MMPMID28716099
Helder MRK
; Stoyles NJ
; Tefft BJ
; Hennessy RS
; Hennessy RRC
; Dyer R
; Witt T
; Simari RD
; Lerman A
J Cardiothorac Surg
2017[Jul]; 12
(1
): 56
PMID28716099
show ga
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 ?-gal antigens but not remove all the non ?-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 ?-gal
epitopes by ELISA. To test for non ?-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 ?-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 ?g/mL and it
increased to 71.9 ± 12.1 ?g/mL average of all time points postoperatively
(p = 0.04). Preoperatively anti-pig IgG in sheep serum was 44.9 ± 1.5 ?g/mL and
it increased to 72.6 ± 6.0 ?g/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
?-gal antigens; however, significant reduction in ?-gal presence on
decellularized cusps was observed. Clinical implications of the non ?-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.
|*Bioprosthesis/adverse effects
[MESH]
|*Heart Valve Prosthesis
[MESH]
|*Immunity, Humoral
[MESH]
|Animals
[MESH]
|Aortic Valve/*surgery
[MESH]
|Calcinosis/etiology/*immunology
[MESH]
|Disease Models, Animal
[MESH]
|Graft vs Host Disease/complications/*immunology
[MESH]
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