Long-term (10-month) pig islet xenograft tolerance using measured total lymphoid irradiation, splenectomy, short-term rabbit antithymocyte globulin, and deoxyspergualin without long-term immunosuppression

Llyung, T; Contreras, Juan L.; Thomas, Francis T.; Pittman, K; Thomas, Judith M.

doi:10.1016/s0041-1345(98)01858-2

Cited by 5 publications

(6 citation statements)

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“…Rats were prepared with 15 Gy of TLI, anti-thymocyte globulin, splenectomy, and deoxyspergualin. Mean graft survival in 30 animals was 302 ± 42 days, confirming and improving upon the Japanese results [63].…”

Section: Rodent-to-rodent Transplantationsupporting

confidence: 82%

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Non‐human to human organ transplantation:Its biologic basis and a potential role for radiation therapy

Halperin

2001

Intl Journal of Cancer

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SUMMARY There is an inadequate supply of human donor organs for transplantation. Xenotransplantation, the transplantation of organs from non-human animals to humans, is one of the potential solutions to this problem. The pig appears to be the preferred donor. For xenotransplantation to be successful, researchers must deal with three fundamental problems: (1) Hyperacute rejection of porcine organs, related to binding of xenoreactive natural antibodies of the recipient to antigens on the graft's endothelial cells, must be overcome. (2) Transmission of animal pathogens to humans must be prevented. Concern about zoonosis is not only directed to the transplant recipient but also concerns the risk that an infectious agent will be transferred from the recipient to the general population. (3) The xenografted organ must be physiologically compatible with the recipient. The physiological function of a pig organ in a human and its ability to sustain a human are problematic. Total lymphoid irradiation (TLI) and thoraco-abdominal irradiation (TAI) as immunosuppressive modalities have been investigated in rodent-to-rodent, large mammals and non-human primates-to-primates, and pig-to-primate models. In certain clinical situations, TLI and TAI may prove to be important components for the preparation of the xenotransplant recipient. Progress in genetic engineering and cloning may soon lead to clinical trials in xenotransplantation.

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Section: Rodent-to-rodent Transplantationsupporting

confidence: 82%

“…TLI plus cyclosporine produced a small but statistically significant prolongation of graft survival (Fig. 4) [11,[63][64][65][66][67][68].…”

Section: Rodent-to-rodent Transplantationmentioning

confidence: 99%

Non‐human to human organ transplantation:Its biologic basis and a potential role for radiation therapy

Halperin

2001

Intl Journal of Cancer

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“…Undoubtedly, the problems in obtaining a good quality graft, especially of porcine islets, have in many instances contributed substantially. Apart from a series of sparsely documented studies (13, 20, 30), two recent articles reported successful transplantation of adult porcine islets in the rat (21, 32). In both studies the graft survivals were alike and remarkably similar to the present study.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of Long-term Cultured Porcine Islets in the Rat: Prolonged Graft Survival and Recipient Growth on Reduced Immunosuppression

et al. 2010

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To evaluate whether further improvement in porcine islet xenotransplantation is feasible, a number of questions were addressed. Earlier we showed significant improvement in the nude mouse of the porcine islets by selection through long-term culture. Now these islets were tested in the stringent pig-to-rat model. Islets were isolated from adult pigs, cultured for 1.5-3 weeks and transplanted to rats. Possible rejection mechanisms were assessed by interference of the cellular response with cyclosporine A (CsA), blocking macrophages with gadolinium chloride (GdCl), and suppressing the humoral response with cyclophosphamide. Modifications in graft size and condition were analyzed. Untreated control recipients showed primary nonfunction (PNF). CsA treatment could fully overcome PNF and resulted in graft survival from 10 to over 134 days. Rejection was the main cause of function loss. Although rejection could not be prevented by intensifying the induction therapy, increased maintenance immunosuppression effectively blocked rejection, albeit at the expense of toxicity. Blocking the humoral response was ineffective; all grafts showed PNF. In contrast, depletion of macrophages fully prevented PNF. Combination of GdCl and CsA gave no additional effect, and grafts were rejected between 57 and 162 days. Generally, graft survivals were similar to those reported in the literature; however, long-term cultured islets required much less maintenance immunosuppression. Cessation of graft function was not always due to rejection; in some cases "islet exhaustion" was found, possibly caused by discrepancy between the graft size and the rapidly growing recipient. Neither the presence of damaged islet tissue in the graft nor the size of the graft exerted any influence on graft survival. On rejection, no real infiltration of the graft was seen; destruction gradually processed from the outside. The good functional capability of the cultured islets was illustrated by disappearance of the clinical symptoms and increase in body weight, which almost doubled in the long-term survivors.

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“…TLI plus cyclosporine produced a small but statistically significant prolongation of graft survival (Fig. 4)[11, 63–68].…”

Section: Tli For Xenotransplantation In Animal Modelsmentioning

confidence: 99%

Humans as second orangutans: sense or nonsense?

Stoneking

2009

BioEssays

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Long-term (10-month) pig islet xenograft tolerance using measured total lymphoid irradiation, splenectomy, short-term rabbit antithymocyte globulin, and deoxyspergualin without long-term immunosuppression

Cited by 5 publications

References 1 publication

Non‐human to human organ transplantation:Its biologic basis and a potential role for radiation therapy

Non‐human to human organ transplantation:Its biologic basis and a potential role for radiation therapy

Transplantation of Long-term Cultured Porcine Islets in the Rat: Prolonged Graft Survival and Recipient Growth on Reduced Immunosuppression

Humans as second orangutans: sense or nonsense?

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