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Review
. 2012 Apr;17(2):148-54.
doi: 10.1097/MOT.0b013e3283509120.

Cardiac xenotransplantation: progress and challenges

Guerard W Byrne  1 , Christopher G A McGregor
Affiliations
Review

Cardiac xenotransplantation: progress and challenges

Guerard W Byrne et al. Curr Opin Organ Transplant. 2012 Apr.

Abstract

Purpose of review: Cardiac xenotransplantation (CXTx) remains a promising approach to alleviate the chronic shortage of donor hearts. This review summarizes recent results of heterotopic and orthotopic CXTx, highlights the role of non-Gal antibody in xenograft rejection, and discusses challenges to clinical orthotopic CXTx.

Recent findings: Pigs mutated in the α 1,3 galactosyltransferase gene (GTKO pigs) are devoid of the galactose α1,3 galactose (αGal) carbohydrate antigen. This situation effectively eliminates any role for anti-Gal antibody in GTKO cardiac xenograft rejection. Survival of heterotopic GTKO cardiac xenografts in nonhuman primates continues to increase. GTKO graft rejection commonly involves vascular antibody deposition and variable complement deposition. Non-Gal antibody responses to porcine antigens associated with inflammation, complement, and hemostatic regulation and to new carbohydrate antigens have been identified. Their contribution to rejection remains under investigation. Orthotopic CXTx is limited by early perioperative cardiac xenograft dysfunction (PCXD). However, hearts affected by PCXD recover full cardiac function and orthotopic survival up to 2 months without rejection has been reported.

Summary: CXTx remains a promising technology for treating end-stage cardiac failure. Genetic modification of the donor and refinement of immunosuppressive regimens have extended heterotopic cardiac xenograft survival from minutes to in excess of 8 months.

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Conflict of interest statement

Conflicts of interest

There are no conflicts of interest to report.

Figures

Figure 1
Figure 1
Common histopathologic changes observed in DXR of GTKO organs. The illustration depicts the relative intensity and timing of major histologic features based on analysis of interim biopsies from Gal-positive and GTKO heterotopic cardiac xenografts (14). IgM, vascular antibody binding; MV, myocyte vacuolization; MT, microvascular thrombosis; CN, coagulative necrosis
Figure 2
Figure 2
Immunohistopathology comparison of GTKO hyperacute rejection after heterotopic cardiac xenotransplantation and perioperative cardiac xenograft dysfunction (PCXD) after orthotopic cardiac xenotransplantation. Hyperacute rejection (A – C). PCXD (D – F). Panels show hematoxylin and eosin staining (A and D), vascular IgM deposition (B and E) and vascular C5b deposition (C and F). Panels A – C (Byrne GW, McGregor CGA, et al, 2012 Transplantation, accepted pending revision)
Figure 3
Figure 3
Orthotopic cardiac xenograft survival. The graph summarizes the published results for pig-to-primate cardiac xenotransplantation based on recipient survival. Values are based on the data reported in references (–46).
See this image and copyright information in PMC

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