Donor-specific HLA antibodies after fresh decellularized vs cryopreserved native allograft implantation.

This study aims to compare the immunogenicity of fresh decellularized with cryopreserved native heart valve allografts to identify potential immunological risks in subsequent organ transplantations. We measured the induction of allogeneic HLA class I and II specific antibodies and characterized donor-specific antibodies by Luminex-based single beads assay in both groups. Serum samples were collected before valve replacement, at 3 and 24 months postoperatively. Donor-specific HLA antibodies were assessed positive if the mean fluorescent intensity (MFI) was >1000. Between November 2016 and April 2017 patients with fresh decellularized homografts (n = 4) and cryopreserved native homografts (n = 4) were analyzed. Patients receiving cryopreserved native allografts reacted with broad HLA-specific antibody response. Antibodies were directed against mismatched HLA antigens of the donors but also against HLA specificities not present on the homograft with many antibodies having mean fluorescence intensity values >10 000. While HLA class I specific antibodies showed a significant increase (P = .002) in their MFI values on day 90, HLA class II specific antibodies did not show a significant increase (P = .069). In the fresh decellularized homografts group, no significant antibody induction was observed. Consequently, the native group presented significantly higher MFIs for HLA antibodies on day 90 compared with the patients receiving decellularized allografts (P = .021). No detectable HLA antibody response was observed after implantation of decellularized in comparison with cryopreserved native allografts. Lower immunogenicity as compared with native homografts might increase the chance of receiving a transplant if will be required later in the life of the patients.

Decellularized aortic allografts versus pulmonary autografts for aortic valve replacement in the growing sheep model: haemodynamic and morphological results at 20 months after implantation.

OBJECTIVES: Pulmonary autografts (PAs) represent the substitute of choice for aortic valve (AV) replacement, especially in children and young adults. Similarly, decellularized aortic valve allografts (DAVAs) have shown excellent mid-term function when implanted in the systemic circulation. The aim of this study was to compare the performance of DAVAs with that of pulmonary autografts after a Ross procedure in the growing sheep model. METHODS: AV root replacement was performed in female lambs (25 ± 3.4 kg) using either DAVAs (n = 5) or pulmonary autografts (n = 5) as in the Ross procedure. Sheep undergoing the Ross procedure received a decellularized pulmonary allograft in place of pulmonary valve. Haemodynamics was investigated by echocardiography and magnetic resonance imaging. The roots were explanted at 20 months and examined by histology to determine the degree of repopulation and quality of the extracellular matrix, and by immunohistochemistry to characterize the repopulating cells. RESULTS: The mean valve diameter increased from 16 to 21 and from 16 to 25 mm in DAVAs and PAs, respectively. At explantation, one PA and one DAVA exhibited moderate insufficiency. Significant differences in transvalvular gradient were only found in PAs between implantation and prior to explantation. The cusps of all implants were soft, pliable and showed no major signs of degeneration. In the decellularized allografts, cell repopulation occurred at the wall and cusp level with a well-maintained, three-layered cusp structure. Ventricular cusp surface of decellularized allografts was more strongly repopulated than the arterial surface. Cusps were covered with cells positive for endothelial markers and were also repopulated by interstitial cells. CONCLUSIONS: DAVAs and PAs provide adequate haemodynamics after AV replacement in the growing sheep. While decellularized grafts are repopulated by endothelial and interstitial cells, autografts maintain in general their native cell distribution. Maintenance of valvular competence during enlargement of the valve ring is, in our opinion, representative of the capacity for physiological growth in both graft types.