In Vitro Recognition and Impairment of Pig Islet Cells by Baboon Immune Cells

Lalain, Sandrine; Gianello, Pierre; Gouin, E.; Saı̈, Pierre

doi:10.1097/00007890-200111150-00012

Cited by 3 publications

(3 citation statements)

References 21 publications

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“…It is noteworthy that even in the presence of this immune reaction, porcine islets were able to remain functional and maintain normoglycemia. This immune response must have been caused by some type of indirect recognition mechanism (42). Questions could be raised about possible complement mediated damage, as Roos et al demonstrated that both anti‐pig IgG and IgM could activate complement with subsequent cytotoxicity (43).…”

Section: Discussionmentioning

confidence: 99%

Survival of Microencapsulated Adult Pig Islets in Mice In Spite of an Antibody Response

Duvivier‐Kali

Omer

López-Ávalos

et al. 2004

American Journal of Transplantation

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The aim of this study was to assess the capacity of simple alginate capsules to protect adult pig islets in a model of xenotransplantation. Adult pig islets were microencapsulated in alginate, with either single alginate coats (SAC) or double alginate coats (DAC), and transplanted into the streptozotocininduced diabetic B6AF1 mice. Normalization of glucose levels was associated with an improvement of the glucose clearance during intravenous glucose tolerance tests. After explantation, all mice became hyperglycemic, demonstrating the efficacy of the encapsulated pig islets. Explanted capsules were mainly free of fibrotic reaction and encapsulated islets were still functional, responding to glucose stimulation with a 10-fold increase in insulin secretion. However, a significant decrease in the insulin content and insulin responses to glucose was observed for encapsulated islets explanted from hyperglycemic mice. An immune response of both IgG and IgM subtypes was detectable after transplantation. Interestingly, there were more newly formed antibodies in the serum of mice transplanted with SAC capsules than in the serum of mice transplanted with DAC capsules. In conclusion, alginate capsules can prolong the survival of adult pig islets transplanted into diabetic mice for up to 190 days, even in the presence of an antibody response.

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Section: Discussionmentioning

confidence: 99%

Survival of Microencapsulated Adult Pig Islets in Mice In Spite of an Antibody Response

Duvivier‐Kali

Omer

López-Ávalos

et al. 2004

American Journal of Transplantation

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“…Hanganutziu-Deicher (HD) antigens and other sialic acid an-The maximum number of islets reported to be success-tigens have been shown to account for significant anti-suggesting more Th2 than Th1 activity (70). The importance of CD4 + T cells was also demonstrated by Fried-genicity of adult pig islets in vitro (61).…”

Section: Immunological Response To Transplanted Isletsmentioning

confidence: 99%

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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“…Whilst it is broadly accepted that the most significant cause of porcine islet rejection in the primate is the cell-mediated response [117][118][119], porcine islets are nonetheless susceptible to damage and destruction mediated by anti-pig antibodies and complement [120][121][122].…”

Section: Porcine Islets and Humoral Rejection Following Transplantatimentioning

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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In Vitro Recognition and Impairment of Pig Islet Cells by Baboon Immune Cells

Cited by 3 publications

References 21 publications

Survival of Microencapsulated Adult Pig Islets in Mice In Spite of an Antibody Response

Survival of Microencapsulated Adult Pig Islets in Mice In Spite of an Antibody Response

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

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

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