Effect of Anticomplement Agent K76 Cooh on Hamster-to-Rat and Guinea Pig-to-Rat Heart Xenotransplantation1

Tanaka, Mitsuko; Murase, Noriko; Ye, Qing; Miyazaki, Wasei; Nomoto, Minoru; Miyazawa, Hironari; Manez, Rafael; Toyama, Y; Demetris, Anthony J.; Todo, Satoru; Starzl, Thomas E.

doi:10.1097/00007890-199609150-00025

Cited by 19 publications

(6 citation statements)

References 27 publications

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“…In a C6 deficient PVG rat strain a prolonged mean GS to 6.1 days was reported (265). These data are in accordance with the limited effect of COF treatment (213,228) and preliminary data on K76, a C5 convertase inhibitor, which failed to prolong GS (266).…”

Section: Data From Immunodeficient Recipientssupporting

confidence: 87%

Pathogenesis and mechanisms of graft rejection in concordant xenotransplantation with special reference to hamster‐to‐rat cardiac transplantation

STEINBRÜCHEL

1996

APMIS

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Section: Data From Immunodeficient Recipientssupporting

confidence: 87%

Pathogenesis and mechanisms of graft rejection in concordant xenotransplantation with special reference to hamster‐to‐rat cardiac transplantation

STEINBRÜCHEL

1996

APMIS

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“…One limitation of this approach in the experimental setting is that evaluation of composite EC-MSC islet grafts in small animal models are not easily performed because of several significant species-specific differences in important areas such as angiogenesis, tissue repair, and innate immunity (31). Also, severely immunodeficient mice (SCID, nu/nu, and Rag) trigger strong innate immune responses that mainly target the vasculature of a transplanted organ due to the phylogenetic disparity between the two species, i.e., human-to-mouse is a discordant xenotransplantation model triggering activation of neutrophils, natural killer cells, macrophages, the complement and coagulation systems, and naturally occurring xenoreactive antibodies (32)(33)(34)(35)(36)(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

Formation of Composite Endothelial Cell–Mesenchymal Stem Cell Islets

et al. 2008

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OBJECTIVE-Mesenchymal stem cells (MSCs) contribute to endothelial cell (EC) migration by producing proteases, thereby paving the way into the tissues for ECs. MSCs were added to our previously described composite EC islets as a potential means to improve their capacity for islet angiogenesis.RESEARCH DESIGN AND METHODS-Human islets were coated with primary human bone marrow-derived MSCs and dermal microvascular ECs. The capacity of ECs, with or without MSCs, to adhere to and grow into human islets was analyzed. The survival and functionality of these composite islets were evaluated in a dynamic perifusion assay, and their capacity for angiogenesis in vitro was assessed in a three-dimensional fibrin gel assay.RESULTS-ECs proliferated after culture in MSC-conditioned medium, and MSCs improved the EC coverage threefold compared with EC islets alone. Islet survival in vitro and the functionality of the composite islets after culture were equal to those of control islets. The EC-MSC islets showed a twofold increase in total sprout formation compared with EC islets, and vascular sprouts emanating from the EC-MSC-islet surface showed migration of ECs into the islets and also into the surrounding matrix, either alone or in concert with MSCs. T he islets of Langerhans are micro-organs, with afferent and efferent blood vessels connecting the capillary network of the islets to the circulation system (1). Intra-islet endothelial cells (ECs) are fenestrated, and the density of the capillary network in the islets is ϳ10 times higher than that of the surrounding exocrine tissue (2,3). During the process of islet isolation before transplantation, the ECs in the islets lose their external vascular support; this situation contributes to their dedifferentiation, apoptosis, and necrosis during subsequent in vitro culture (4). CONCLUSIONS-ECThe formation of new capillaries during revascularization is a complex process that involves digestion of the vascular wall by proteases and the migration, proliferation, and differentiation of ECs (5). When blood vessels are assembled, ECs produce platelet-derived growth factor, which attracts supportive cells, including mesenchymal stem cells (MSCs) that can differentiate into pericytes (6).We hypothesized that adding MSCs to our previously described composite EC islets (7) might improve the adherence of the ECs to the islets and subsequent vascularization because MSCs contribute to EC migration by producing proteases, thereby paving the way into the surrounding tissue for the immature EC sprouts (8). MSCs have also been shown to upregulate the expression of angiopoietin and vascular endothelial growth factor (VEGF) in ECs, contributing to an increase in angiogenesis and stabilization of the vasculature (9). Moreover, MSCs have been shown to possess important immune-modulating properties (10), and they do not trigger adaptive immune reactions, which could make them ideal in islet transplantation setting (11,12).The present study describes a gentle and reproducible technique for forming EC-MSC i...

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“…This contrast to the normal pathology observed in hDAF hearts and non‐transgenic hearts transplanted in recipients that underwent EIA before Tx, suggesting that the xenograft underwent HAR, not AHXR. The prolonged beating may be due to the non‐functionality of the model, as has been shown in other experimental models of heterotopic heart xenotransplantation, where a delay between rejection of the organ and cessation of beating was observed [14].…”

Section: Discussionmentioning

confidence: 99%

Failure to deplete anti‐Galα1‐3Gal antibodies after pig‐to‐baboon organ xenotransplantation by immunoaffinity columns containing multiple Galα1‐3Gal oligosaccharides

Máñez

Doménech

Centeno

et al. 2004

Xenotransplantation

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The EIA reduces anti-alphaGal and APHA antibodies, preventing the HAR of non-transgenic pig hearts transplanted in baboons, as does hDAF expression. However, EIA does not modify the level of anti-alphaGal IgM and APHA antibodies after Tx nor the AHXR of either non-transgenic or hDAF pig organs. The increase in anti-alphaGal IgM after Tx was similar for the different antibodies of the anti-alphaGal polymorphism, and was only partially neutralized in vitro with the specific alphaGal oligosaccharide.

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Effect of Anticomplement Agent K76 Cooh on Hamster-to-Rat and Guinea Pig-to-Rat Heart Xenotransplantation1

Cited by 19 publications

References 27 publications

Pathogenesis and mechanisms of graft rejection in concordant xenotransplantation with special reference to hamster‐to‐rat cardiac transplantation

Pathogenesis and mechanisms of graft rejection in concordant xenotransplantation with special reference to hamster‐to‐rat cardiac transplantation

Formation of Composite Endothelial Cell–Mesenchymal Stem Cell Islets

Failure to deplete anti‐Galα1‐3Gal antibodies after pig‐to‐baboon organ xenotransplantation by immunoaffinity columns containing multiple Galα1‐3Gal oligosaccharides

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