A Technique for Transplanting Pancreatic Islets as a Vascularized Graft and Prevention of Rejection With Cyclosporin A

H, Reece-Smith; Homan, William P.; DuToit, Don; McShane, Paul; Morris, Peter J.

doi:10.1097/00007890-198106000-00008

Cited by 40 publications

(10 citation statements)

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“…The vulnerability of islets to alloimmune attack would therefore seem to be attributable to the manner in which isolated islets are transplanted, including their small size, exposed surface, and intravascular location, rather than to intrinsic differences between the effector mechanisms of the rejection of islets and other tissues and organs . This explanation is supported by experiments that have shown that isolated islet allografts transplanted within a vascularized organ allograft, either as a composite islet/kidney (39) or islet/liver (15) graft or within the whole pancreas (16,17) undergo rejection at a slower rate, commensurate with rejection of the organ bearing the islets .…”

Section: Discussionmentioning

confidence: 93%

“…The failure to extract insulin from any of the kidneys grafted originally with either 200 or 400 allogeneic islets alone is compatible with the destruction of all allografted tissue within 21 d of transplantation. Previously published metabolic and histological data have demonstrated that both LEW and PVG islets grafted into untreated DA recipients are destroyed within several days of intraportal transplantation (20,38,39), and within N1 wk of renal subcapsular transplantation (20,25).…”

Section: Discussionmentioning

confidence: 99%

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The specificity of rejection and the absence of susceptibility of pancreatic islet beta cells to nonspecific immune destruction in mixed strain islets grafted beneath the renal capsule in the rat.

Sutton

Gray

McShane

et al. 1989

The Journal of Experimental Medicine

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The specificity of rejection of isolated pancreatic islets was examined in the rat using a quantitative model in which syngeneic (DA) or a mixture of syngeneic and allogeneic (DA and LEW or PVG) islets were implanted beneath the capsule of the kidney of nondiabetic normal rats (DA). 3 wk after transplantation total insulin extraction assays of the kidney with its islet implant together with immunohistological examination of the site of transplantation for evidence of syngeneic or allogeneic tissue demonstrated the total destruction of allogeneic islets without any evidence of damage to syngeneic islets either distant or in immediate proximity to allogeneic islets. Pancreatic islets, and especially beta cells, appear to be particularly vulnerable to the effector arm of both autoimmune and alloimmune responses, a vulnerability that has been attributed to the cytotoxic effects of lymphokines, notably IL-1, released in both autoimmune and alloimmune responses. The experiments reported here demonstrate not only the exquisite specificity of the allograft reaction but are not compatible with a hypothesis that B cells within an intact islet are nonspecifically susceptible to destruction by lymphokines.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

The specificity of rejection and the absence of susceptibility of pancreatic islet beta cells to nonspecific immune destruction in mixed strain islets grafted beneath the renal capsule in the rat.

Sutton

Gray

McShane

et al. 1989

The Journal of Experimental Medicine

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“…The minimum effective dosage required to prolong survival of isolated pancreatic islets in incompatible rats is considerably in excess of that needed to produce indefinite renal allograft survival in the same species [47,137]. Isolated pancreatic islets implanted under the renal capsule have also been transplanted to CsA treated allogeneic diabetic hosts with indefinite survival of the islets [138]. More spectacular has been the marked prolongation of dog lung allograft survival achieved by VEITH and his colleagues with CsA alone or incombination with other immunosuppressants [117,165].…”

Section: (E) Graft Rejectionmentioning

confidence: 99%

Cyclosporine: Immunology, toxicity and pharmacology in experimental animals

1984

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Cyclosporine (CsA) is the first of a new order of pharmacological immune suppressants and represents a significant advance in the clinical control of graft rejection. In laboratory animals, its capacity to prolong allograft survival has been well documented, including reports of indefinite donor-specific immunological tolerance after shortterm CsA treatment. There is also evidence that CsA can inhibit the onset or progress of a variety of experimental autoimmune diseases. Underlying these properties of the drug is its capacity to selectively interfere with T helper cell activation and lymphokine production, although some direct effects on B cells have also been reported. In addition, sparing of suppressor cells may in part explain the mode of action of CsA which, at the molecular level, is not understood. CsA-induced nephrotoxicity in the rat has been extensively studied and is characterized by reversible proximal tubular cell damage. This problem may be aggravated by concomitant administration of other potentially nephrotoxic drugs, such as gentamicin, or by therapeutic agents which interfere with the metabolism of CsA. CsA is metabolized in the liver and excreted in the bile. Although the pathway of hepatic metabolism of CsA has not been precisely elucidated, animal studies suggest that agents capable of inducing metabolism of the drug CsA could be used to alleviate its nephrotoxic properties.

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“…Another improvement was the utilization of the renal capsule graft site, which provides one of the most vasculogenic sites for transplantation, thus resulting in a high take-rate and optimal growth. The renal capsule site has been used for growth of rat pancreatic islets (Reece-Smith et al 1981), mouse neural lobes (Stach-Chilf et al 1981), human gliomas (Weizsacker et al 1983), human tumor xenografts (Aamdal et al 1985), human fetal mammalian reproductive tract (Taguchi et al 1984), mouse mammary glands (Wiesen et al 1999) and a variety of other cells and tissues. Incorporating these modifications, a novel method was used to grow human breast epithelium in vivo, using organoids from reduction mammoplasties combined with either mouse or human mammary fibroblasts embedded in a collagen gel that was transplanted under the renal capsule of female nude mice (Parmar et al 2002).…”

Section: Human Mammary Cells In Culture: In Vitro Studies Of Human Epmentioning

confidence: 99%

Epithelial–stromal interactions in the mouse and human mammary gland in vivo

Parmar¹,

Cunha²

2004

Endocr Relat Cancer

163

147

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This review deals with the development and hormonal responses of mouse and human mammary glands. A major focus of the review is the role of mesenchymal-epithelial interactions in embryonic mammary development and the role of stromal-epithelial interactions in mammary gland biology. Finally, we present a new model for studying growth, differentiation and hormonal response in human breast epithelium grown in vivo in nude mouse hosts. This new model involves the construction of tissue recombinants composed of human or mouse mammary fibroblasts plus human breast epithelium in polymerized collagen gels. In the model, mouse mammary fibroblasts and human breast fibroblasts appear to support the normal differentiation and growth of human breast epithelium equally. This observation raises the possibility of using mouse mammary fibroblasts from various mutant mice to assess the role of specific paracrine-acting gene products in human mammary gland biology and carcinogenesis.

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A Technique for Transplanting Pancreatic Islets as a Vascularized Graft and Prevention of Rejection With Cyclosporin A

Cited by 40 publications

References 0 publications

The specificity of rejection and the absence of susceptibility of pancreatic islet beta cells to nonspecific immune destruction in mixed strain islets grafted beneath the renal capsule in the rat.

The specificity of rejection and the absence of susceptibility of pancreatic islet beta cells to nonspecific immune destruction in mixed strain islets grafted beneath the renal capsule in the rat.

Cyclosporine: Immunology, toxicity and pharmacology in experimental animals

Epithelial–stromal interactions in the mouse and human mammary gland in vivo

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