The Immunologic Basis of Xenograft Heart Valve Deterioration

• Author / Creator

  Bozso, Sabin J

• Valvular heart disease (VHD) is a common diagnosis with an approximate prevalence of 2.5% of the total population having moderate to severe VHD [1, 2]. The most common treatment for end-stage VHD is surgical valve replacement with constructs categorized into three classes: mechanical valves, homografts and xenografts. Given the need for lifelong anticoagulation with mechanical valves and the significant lack of availability of homografts, xenografts have become the most common valve type implanted clinically. The main issue facing xenograft tissue heart valve (XTHV) prostheses is their rate of structural valve deterioration (SVD) over time, leading to hemodynamic dysfunction and clinical symptoms of valve obstruction [3]. Emerging evidence from laboratory and clinical investigations suggests that XTHVs generate an immune response that has been implicated in the failure of these grafts [4-9]. To address these shortcomings, several attempts have been made to create functional heart valve replacements, using decellularized xenograft matrices with autologous cell recellularization to mask the xenograft scaffold from host immune recognition. However, to date, it remains unclear what effect an autologous recellularized xenograft has on the immune response in the host. Therefore, the objectives of this thesis are to establish the role of the immune system in prosthesis failure by analyzing explanted XTHVs developing SVD, to attenuate the immune response with autologous recellularized xenograft heart valves in a human, in-vitro and small animal, in-vivo model, and finally to assess the effect of immunomodulatory medication on clinical rates of SVD amongst patients receiving a XTHV. This work will lead to a better understanding of the immune mechanisms elicited by XTHVs and autologous recellularized xenografts, allowing us to ascertain if this approach may be a viable option for future valve constructs.

• Subjects / Keywords

  • surgery
  • xenograft
  • valve
  • recellularization
  • immunology

• Graduation date

  Fall 2021

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-f0w6-xk21

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.