The Utility of Right Ventricular Endomyocardial Biopsy for the Diagnosis of Xenograft Rejection After CD46 Pig-to-Baboon Cardiac Transplantation

Ricci, Davide; Tazelaar, Henry D.; Miyagi, Naoto; Rao, Vinay; Pedersen, Rachel; Kremers, Walter K.; Byrne, Guerard W.; McGregor, Christopher G.A.

doi:10.1016/j.healun.2007.07.028

Cited by 9 publications

(6 citation statements)

References 21 publications

(9 reference statements)

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“…More aggressive salvage therapies may also include B-cell and plasma cell depletion and complement inhibition [ 105 , 106 ]. In CXTx, there are few studies which have attempted to diagnose and treat presumptive rejection episodes, most of these after hCXTx [ 9 , 25 , 33 , 107 – 109 ]. Putative rejection episodes were diagnosed based on biochemical markers (troponin T, AST), graft contractility, telemetric measures of cardiac performance, and echocardiography.…”

Section: Diagnosis and Treatment Of Rejectionmentioning

confidence: 99%

“…Putative rejection episodes were diagnosed based on biochemical markers (troponin T, AST), graft contractility, telemetric measures of cardiac performance, and echocardiography. Serial biopsies after oCXTx will likely be applicable for diagnosis of rejection [ 109 – 111 ], but the difficulty of obtaining endomyocardial biopsies in NHPs has limited their exploration in animal models. When presumptive rejection episodes were treated using steroids, or steroids and ATG, there was no evidence for reversal of rejection, and, unsurprisingly, in some instances, excessive antirejection therapy increased the frequency of infectious complications [ 9 , 25 ].…”

Section: Diagnosis and Treatment Of Rejectionmentioning

confidence: 99%

See 1 more Smart Citation

Porcine to Human Heart Transplantation: Is Clinical Application Now Appropriate?

McGregor

Byrne

2017

Journal of Immunology Research

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Cardiac xenotransplantation (CXTx) is a promising solution to the chronic shortage of donor hearts. Recent advancements in immune suppression have greatly improved the survival of heterotopic CXTx, now extended beyond 2 years, and life-supporting kidney XTx. Advances in donor genetic modification (B4GALNT2 and CMAH mutations) with proven Gal-deficient donors expressing human complement regulatory protein(s) have also accelerated, reducing donor pig organ antigenicity. These advances can now be combined and tested in life-supporting orthotopic preclinical studies in nonhuman primates and immunologically appropriate models confirming their efficacy and safety for a clinical CXTx program. Preclinical studies should also allow for organ rejection to develop xenospecific assays and therapies to reverse rejection. The complexity of future clinical CXTx presents a substantial and unique set of regulatory challenges which must be addressed to avoid delay; however, dependent on these prospective life-supporting preclinical studies in NHPs, it appears that the scientific path forward is well defined and the era of clinical CXTx is approaching.

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Section: Diagnosis and Treatment Of Rejectionmentioning

confidence: 99%

Section: Diagnosis and Treatment Of Rejectionmentioning

confidence: 99%

Porcine to Human Heart Transplantation: Is Clinical Application Now Appropriate?

McGregor

Byrne

2017

Journal of Immunology Research

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“…Ricci et al [43] explored the value of right ventricular endomyocardial biopsy for the diagnosis of rejection after pig-to-baboon heterotopic cardiac xenoTx. Their results indicated that delayed xenograft rejection is a widespread process involving both right and left ventricles similarly.…”

Section: Cell Transplantation As a Form Of Xenotransplantationmentioning

confidence: 99%

Update: cardiac xenotransplantation

Ekser¹,

Cooper²

2008

Current Opinion in Organ Transplantation

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Purpose of review-To review the latest development in cardiac xenotransplantation in small and large animal models and related in vitro studies.Recent findings-With the recent introduction of α1,3-galactosyltransferase gene-knockout (GT-KO) pig organs for xenotransplantation, improved cardiac graft survival has been obtained. However, this experience has demonstrated the importance of pig antigens other than Galα1,3Gal (Gal) antigens (so-called nonGal antigens) as targets for primate anti-pig antibodies. Several in vitro studies have confirmed that, although the incidence and levels of anti-nonGal antibodies in non-human primates and humans are significantly less when compared with total anti-pig antibodies (i.e., anti-Gal + antinonGal), they can result in complement-mediated lysis of GT-KO pig cells. More recently, it has been demonstrated that regulatory T cells (Treg) suppress the cellular xenogeneic response, thus potentially preventing or reducing T cell-mediated rejection. The importance of thrombotic microangiopathy as a feature of the immune/inflammatory response and incompatibilities between the coagulation-anticoagulation systems of pig and primate are receiving increasing attention. Development of GT-KO pigs transgenic for one or more 'anti-thrombotic' genes, e.g., CD39 or tissue factor pathway inhibitor, may contribute to overcoming these problems.Summary-Although GT-KO pigs have provided an advance over wild-type pigs as a source of Organs for transplantation into primates, further genetic modification of GT-KO pigs is required to overcome the remaining immune barriers before a clinical trial of cardiac xenotransplantation can be contemplated.

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“…Ricci et al. analyzed the histopathology of CD46‐transgenic pig hearts transplanted into baboons for the diagnosis of xenograft rejection [6]. They showed that linear regression analysis of histology scores from endomyocardial biopsies and cross sections of explanted hearts equally represented histology of right and left ventricle tissue.…”

Section: Preclinical Studiesmentioning

confidence: 99%

“…Authors concluded that delayed xenograft rejection was a widespread process involving similarly both right and left ventricles. Histological assessment of the right ventricle by endomyocardial biopsy could therefore be an effective method for monitoring xenograft rejection after cardiac xenotransplantation [6].…”

Section: Preclinical Studiesmentioning

confidence: 99%