Cardiac Xenotransplantation: Future and Limitations

Ogata, Kyoichi; Platt, Jeffrey L.

doi:10.1159/000075995

Cited by 16 publications

(13 citation statements)

References 85 publications

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“…Transplantation is the best therapy to "cure" these patients, however, fewer than 5% of those who need a cardiac transplant receive one in the United States each year (1). To solve the severe shortage of human heart donors, xenotransplantation may offer a great source to these patients who are desperately in need of an organ.…”

mentioning

confidence: 99%

CD80/CD86 Costimulation Regulates Acute Vascular Rejection

Hosiawa

Wang²,

DeVries

et al. 2005

The Journal of Immunology

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Xenotransplantation may provide the only solution to the shortage of human donor organs. Although hyperacute rejection associated with xenotransplantation can now be overcome, acute vascular rejection (AVR) remains a primary barrier to xenotransplantation. To date, standard immunosuppressive agents fail to block AVR or prolong xenograft survival. The present study was undertaken to determine the role of CD80/CD86 costimulatory molecules in regulating AVR. Lewis rat hearts were transplanted heterotopically into wild-type or IL-12, CD80- or CD86-deficient C57BL/6 mice. Wild-type recipients were treated with CD80 or CD86 neutralizing Ab with and without daily cyclosporin A (CsA, 15 mg/kg). Transplanted hearts in untreated wild-type recipients were rejected on postoperative days (POD) 17–21 and showed cell-mediated rejection (CMR) and AVR pathologies. In contrast, transplanted hearts in IL-12 and CD80 recipients or wild-type recipients treated with CD80 neutralizing Ab were rapidly rejected on POD 5 and 6 with AVR pathology. Interestingly, hearts transplanted into CD86 knockout recipients or wild-type recipients treated with CD86 neutralizing Ab underwent CMR on POD 17. Finally, blockade of CD86 but not CD80 rendered xenograft recipients sensitive to daily CsA therapy, leading to indefinite xenograft survival. To conclude, we demonstrate that AVR can be overcome by blocking the CD86 costimulatory pathway. Furthermore, we demonstrate that CD80 and CD86 have opposing roles in regulation of xenotransplantation rejection, where CD80 drives CMR and attenuates AVR while CD86 drives AVR. Most strikingly, indefinite xenograft survival can be achieved by suppressing AVR with CD86 neutralization in combination of CsA therapy, which inhibits CMR.

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mentioning

confidence: 99%

CD80/CD86 Costimulation Regulates Acute Vascular Rejection

Hosiawa

Wang²,

DeVries

et al. 2005

The Journal of Immunology

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“…1 The successful allotransplant has led to an established therapy for patients with end-stage liver diseases as a great success in the twentieth century. 2 However, the number of patients requiring liver transplant far outweighs the availability of suitable graft. 3 Also, an increasing number of patients, being referred for liver transplant, have created a crisis in donor organ availability.…”

Section: Introductionmentioning

confidence: 99%

Appropriate Donor Size for Porcine Liver Xenotransplant

Soleimani

Fonouni²,

Esmaeilzadeh³

et al. 2012

Exp Clin Transplant

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“…Organ transplantation is considered the preferred solution for the treatment of terminal organ failure [28]. However, there has always been a serious shortage of suitable human donors [13].…”

Section: Introductionmentioning

confidence: 99%

Multidetector computed tomographic angiography evaluation of micropig major systemic vessels for xenotransplantation

et al. 2011

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Due primarily to the increasing shortage of allogeneic donor organs, xenotransplantation has become the focus of a growing field of research. Currently, micropigs are the most suitable donor animal for humans. However, no standard method has been developed to evaluate the systemic vascular anatomy of micropigs and standard reference values to aid in the selection of normal healthy animals as potential organ donors are lacking. Using 64-channel multidetector row computed tomographic angiography (MDCTA), we evaluated morphological features of the major systemic vessels in micropigs and compared our results to published human data. The main vasculature of the animals was similar to that of humans, except for the iliac arterial system. However, diameters of the major systemic vessels were significantly different between micropigs and humans. Specifically, the diameter of the aortic arch, abdominal aorta, external iliac artery, and femoral artery, were measured as 1.50 ± 0.07 cm, 0.85 ± 0.06 cm, 0.52 ± 0.05 cm, and 0.48 ± 0.05 cm, respectively, in the micropigs. This MDCTA data for micropig major systemic vessels can be used as standard reference values for xenotransplantation studies. The use of 64-channel MDCTA enables accurate evaluation of the major systemic vasculature in micropigs.

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Cardiac Xenotransplantation: Future and Limitations

Cited by 16 publications

References 85 publications

CD80/CD86 Costimulation Regulates Acute Vascular Rejection

CD80/CD86 Costimulation Regulates Acute Vascular Rejection

Appropriate Donor Size for Porcine Liver Xenotransplant

Multidetector computed tomographic angiography evaluation of micropig major systemic vessels for xenotransplantation

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