Xenografting of pig islets in monkeys does not result in hyperacute rejection

Rijkelijkhuizen, J.K.R.A; Ossevoort, Miriam; Ringers, J.; Burg, M.P.M. van der; Kühn, Eva; Wubben, Jacqueline; Haanstra, Krista G.; Bouwman, E; Jonker, Margreet

doi:10.1016/s0041-1345(00)01122-2

Cited by 6 publications

(4 citation statements)

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“…Cortico-ACKNOWLEDGMENTS: We thank Agnes C. Zachoszcz for steroids used to be constituents of immunosuppressive to some more conventional agents (49). When an anti- Porcine C-peptide levels (18,19,27,38,49,57,102,108) ment regulatory proteins on islets of Langerhans: A comand histology of the graft (Table 3) At the present time, it would seem that adult porcine…”

Section: Immunological Response To Transplanted Isletsmentioning

confidence: 85%

“…However, Soderlund et al showed that necrosis of the graft was evident on the first day, and was progressive to day 3; the necrotic areas contained polymorphonuclear cells (106). Spreading the islets over a larger surface area reduces the risk of ischemic injury (102,106).…”

Section: Humanmentioning

confidence: 99%

“…Histology from subrenal capsu-vival of porcine islets in monkeys was extended significantly; cellular infiltration in subrenal capsular islet lar and intraportal grafts showed increasing T-cell infiltration before graft loss, with few B cells, macrophages, grafts was delayed from 11 to 53 days (102). Immunosuppressive regimens containing sirolimus and NK cells (102).…”

Section: Immunological Response To Transplanted Isletsmentioning

confidence: 99%

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Pig-to-Nonhuman Primate Islet Xenotransplantation: A Review of Current Problems

et al. 2006

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Islet allotransplantation has been shown to have potential as a treatment for type 1 diabetic patients. Xenotransplantation, using the pig as a donor, offers the possibility of an unlimited number of islets. This comprehensive review focuses on experience obtained in pig-to-nonhuman primate models, particularly with regard to the different types of islets (fetal, neonatal, adult) and isolation procedures used, and the methods to determine islet viability. The advantages and disadvantages of the methods to induce diabetes (pancreatectomy, streptozotocin) are discussed. Experience in pig-to-nonhuman primate islet transplantation studies is reviewed, including discussion of the possible mechanisms of rejection and the immunosuppressive regimens used. The research carried out to date has led to workable animal models to study islet xenotransplantation, but several questions regarding methodology remain unanswered, and details of these practicalities require to be adequately addressed. The encouraging porcine islet survival reported recently provides an indicator for future immunosuppressive regimens.

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Section: Immunological Response To Transplanted Isletsmentioning

confidence: 85%

Section: Humanmentioning

confidence: 99%

Section: Immunological Response To Transplanted Isletsmentioning

confidence: 99%

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Pig-to-Nonhuman Primate Islet Xenotransplantation: A Review of Current Problems

et al. 2006

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“…In this context, cellular transplants, and therefore islet transplants, are believed to be uniquely resistant to the HAR process. Supporting this notion, several groups report porcine islet survival for various periods of time following transplantation into primates [117,119,[124][125][126]. In contrast, studies assessing islet survival following rabbit-to-primate transplantation have demonstrated damage of the transplanted islets within 6 hours [127].…”

Section: Islets Are Less Susceptible To Har Phenomenamentioning

confidence: 99%

Antibody Mediated Rejection in Pig-To-Nonhuman Primate Xenotransplantation Models

Severo¹,

Bosio²,

Besenzon³

et al. 2005

CDTCHD

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Antibody-mediated mechanisms are central to the rejection that occurs when pig organs are transplanted into primates. In this article, the histopathological features of the humoral rejection process in these species combinations, namely hyperacute rejection and acute humoral xenograft rejection, will be illustrated. The profile of the natural and elicited antibodies involved will also be discussed. It has now been demonstrated that the natural immune response to a porcine xenograft is primarily directed to Galalpha1-3Gal (alphaGal) specificities, whilst the elicited immune response is directed to both alphaGal and non-alphaGal antigens. The principal characteristics of anti-alphaGal, anti-non-alphaGal and polyreactive antibodies will be described, together with the identification of the molecules recognised by natural and elicited xenoreactive antibodies. The role of the humoral immune response in the rejection of porcine islets in the primate is still uncertain and the current views on the subject will be discussed. Finally, a concise but comprehensive review of the different strategies that have been attempted to prevent the onset of antibody-mediated rejection is presented. These strategies encompass approaches aimed at interfering with the binding of xenoreactive antibodies with their targets, the use of conventional or novel immunosuppressants and splenectomy. It is undeniable that significant progress has been recently achieved in understanding the humoral rejection process of pig organs transplanted into primates. It is expected that a more comprehensive elucidation of the mechanisms underlying accommodation and tolerance may, in the not too distant future, further extend survival of pig organs transplanted into primates.

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