# Antibody and Cellular Immune Responses in Old α1,3-Galactosyltransferase-Knockout Mice Implanted with Bioprosthetic Heart Valve Tissues

## TL;DR

This study explores how aging affects immune responses to bioprosthetic heart valves in mice, revealing age-related differences in antibody and cellular immunity.

## Contribution

The study introduces the use of Gal KO mice to investigate age-related immune responses to different bioprosthetic heart valve tissues.

## Key findings

- Old Gal KO mice showed decreased anti-Gal IgM levels compared to adults after implantation of Freedom-Solo valves.
- Cellular immune responses were generally lower in old mice, though some valve types still triggered strong immune infiltration.
- The Gal KO mouse model is effective for studying age-related immune differences in bioprosthetic heart valve tissues.

## Abstract

Structural valve deterioration (SVD) remains a key limitation in bioprosthetic heart valve (BHV) usage influenced by patient age. A deeper understanding of SVD pathogenesis, particularly of the immune-mediated processes altering current BHV materials, is therefore critical. To this end, commercially available BHV tissues of bovine, porcine, and equine origin were investigated following subcutaneous implantation into α1,3-galactosyltransferase-knockout (Gal KO) mice. We compared the immune responses between adult and aged animals via histological assessments of explants and measurement of serum anti-galactose α1,3-galactose (Gal) and anti-non-Gal antibodies at 2 months post-implantation. In contrast to adult mice, old Gal KO mice did not show increased levels of serum anti-Gal or -non-Gal antibodies after receiving specific BHV tissue (i.e., Freedom-Solo). Instead, a significant decrease in serum anti-Gal IgM was found in old recipients of Freedom-Solo. Furthermore, the overall cellular immune response was attenuated in explants from old mice compared with adults (i.e., ATS 3f and Crown). Nevertheless, the Freedom-Solo (bovine) and the Hancock-II (porcine) tissues still elicited strong cellular immune infiltration in the old cohorts. Therefore, the Gal KO mouse model offers a valuable platform to investigate age-related differences regarding cellular and humoral immune responses to various BHV tissues, contributing to our understanding of SVD.