The Immune Response to Crosslinked Tissue is Reduced in Decellularized Xenogeneic and Absent in Decellularized Allogeneic Heart Valves. Issue 4 (April 2015)

• Record Type: Journal Article
• Authors: Böer, Ulrike; Schridde, Ariane; Anssar, Marcel; Klingenberg, Melanie; Sarikouch, Samir; Dellmann, Ansgar; Harringer, Wolfgang; Haverich, Axel; Wilhelmi, Mathias
• Is Part Of: International journal of artificial organs. Volume 38:Issue 4(2015:Apr.)
• Page Start: 199
• Page End: 209
• Publication Date: 2015-04
• Subjects: Tissue engineering -- Heart valve -- Decellularization -- Antibody formation -- Inflammation; Artificial organs -- Periodicals; 617.956
• DOI: 10.5301/ijao.5000395
• Languages: English
• ISSNs: 0391-3988

Abstract

Background: The degeneration and failure of xenogeneic heart valves, such as the Matrix P Plus valve (MP-V) consisting of decellularized porcine valves (dec-pV) and equine glutaraldehyde-fixed conduits (ga-eC) have been linked to tissue immunogenicity accompanied by antibody formation. In contrast, decellularized allograft valves (dec-aV) are well-tolerated. Here, we determined tissue-specific antibody levels in patients after implantation of MP-V or dec-aV and related them to valve failure or time period after implantation. Methods and Results: Specific antibodies toward whole tissue-homogenates or alphaGal were determined retrospectively by ELISA analyses from patients who received MP-V with an uneventful course of 56.1 ± 5.1 months (n = 15), or with valve failure after 25.3 ± 14.6 months (n = 3), dec-aV for various times from 4 to 46 months (n = 14, uneventful) and from healthy controls (n = 4). All explanted valves were assessed histopathologically. MP-V induced antibodies toward both tissue components with significantly higher levels toward ga-eC than toward dec-pV (68.7 and 26.65 μg/ml IgG). In patients with valve failure, levels were not significantly higher and were related to inflammatory tissue infiltration. Anti-Gal antibodies in MP-V patients were significantly increased in both, the uneventful and the failure group. In contrast, in dec-aV patients only a slight tissue-specific antibody formation was observed after 4 months (6.24 μg/ml) that normalized to control levels after 1 year. Conclusions: The strong humoral immune response to glutaraldehyde-fixed tissues is reduced in decellularized xenogeneic valves and almost absent in decellularized allogeneic tissue up to 4.5 years after implantation.