Secondary Organ Allografting After a Primary “Bridging” Xenotransplant

Ye, Y; Luo, Yigang; Kobayashi, T; Taniguchi, Shigeki; Li, S; Niekrasz, Marek; Kosanke, Stanley D.; Baker, Judy; Mieles, Luis; Smith, D. M.; Cooper, D. K. C.

doi:10.1097/00007890-199507150-00004

Cited by 29 publications

(20 citation statements)

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“…In addition, patients who no longer have access sites to allow dialysis might be considered. (Present evidence, though very limited, suggests that rejection of a pig kidney would not increase the patient’s sensitization to a potential kidney allograft [54,57,58]. We suggest that the potential benefit to the patient, and the relatively low risk of the procedure, would make such a limited trial ethical.…”

Section: Commentmentioning

confidence: 91%

Current status of pig kidney xenotransplantation

Iwase

Kobayashi

2015

International Journal of Surgery

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Significant progress in life-supporting kidney xenograft survival in nonhuman primates (NHPs) has been associated largely with the increasing availability of pigs with genetic modifications that protect the pig tissues from the primate immune response and/or correct molecular incompatibilities between pig and primate. Blockade of the CD40/CD154 costimulation pathway with anti-CD154 mAb therapy has contributed to prolongation of kidney xenograft survival, although this agent may not be clinically available. An anti-CD40 mAb-based regimen is proving equally successful, but blockade of the CD28/B7 pathway is inadequate. Severe proteinuria were uniformly documented in the early studies of pig kidney xenotransplantation, but whether this resulted from immune injury or from physiological incompatibilities between the species, or both, remained uncertain. Recent experiments suggest it was related to a continuing immune response. Before 2014, the longest survival of a pig kidney graft in a NHP was 90 days, though graft survival >30 days was unusual. Recently this has been extended to >125 days, without features of a consumptive coagulopathy or a protein-losing nephropathy. In conclusion, overcoming the immune, coagulation, and inflammatory responses by the development of precise genetic modifications in donor pigs, along with effective immunosuppressive and anticoagulant/anti-inflammatory therapy is advancing the field towards clinical trials.

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Section: Commentmentioning

confidence: 91%

Current status of pig kidney xenotransplantation

Iwase

Kobayashi

2015

International Journal of Surgery

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“…45 Initial in vitro and in vivo studies demonstrated that sera from baboons previously exposed to pig organs that became sensitized to pig antigens did not develop sensitization to baboon antigens (allosensitization). 71 Later in vitro studies confirmed that, despite the development of high levels of elicited anti-pig Abs, baboons did not develop allosensitization. 72 This would enable a pig organ to be used successfully as a bridge to allotransplantation.…”

Section: The Development Of Ahxr and Tm Can Be Identified By Changes mentioning

confidence: 96%

Pig–to–Non-human Primate Heart Transplantation: Immunologic Progress Over 20 Years

Zhu¹,

Dor²,

Cooper³

2007

The Journal of Heart and Lung Transplantation

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“…Most studies have indicated that antibodies directed to HLA do not cross-react with those directed against pig antigens. Furthermore, although the data are currently limited, a patient who undergoes a pig organ transplant that fails (and develops sensitization to pig antigens) may not be at a disadvantage when receiving a subsequent allotransplant (22, 23). …”

Section: How Far Has Xenotransplantation Research Progressed Today?mentioning

confidence: 99%

The case for xenotransplantation

Cooper

2015

Clinical Transplantation

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The availability of organs and cells from deceased humans for transplantation is not meeting the demand. Xenotransplantation, specifically the transplantation of organs and cells from genetically-engineered pigs, could resolve this problem. Diabetic monkeys have remained normoglycemic and insulin-independent after pig islet transplantation for >1 year, and a pig heterotopic (non-life-supporting) heart transplant recently reached the one-year milestone in a baboon. With these encouraging results, why is it that, with some notable exceptions, research into xenotransplantation has received relatively little support by industry, government funding agencies, and medical charitable foundations? Industry appears reluctant to support research that will take more than 2–3 years to come to clinical trial, and the funding agencies appear to have been “distracted” by the current appeal of stem cell technology and regenerative medicine. It has only been the willingness of living donors to provide organs that has significantly increased the number of transplants being performed worldwide. These altruistic donations are not without risk of morbidity and even mortality to the donor. Although with the best of intentions, we are therefore traversing the Hippocratic Oath of doctors to “do no harm”. This should be a stimulus to fund exploration of alternative approaches, including xenotransplantation.

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Secondary Organ Allografting After a Primary “Bridging” Xenotransplant

Cited by 29 publications

References 0 publications

Current status of pig kidney xenotransplantation

Current status of pig kidney xenotransplantation

Pig–to–Non-human Primate Heart Transplantation: Immunologic Progress Over 20 Years

The case for xenotransplantation

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