Humoral Responses to Pig-to-Baboon Cardiac Transplantation: Implications for the Pathogenesis and Treatment of Acute Vascular Rejection and for Accommodation

McCurry, Kenneth R.; Parker, William; Cotterell, Adrian; Weidner, Bryan C.; Lin, Song; Daniels, Larkin J; Holzknecht, Zoie E.; Byrne, Guerard W.; Diamond, Lisa E.; Logan, John S.; Platt, Jeffrey L.

doi:10.1016/s0198-8859(97)00229-2

Cited by 87 publications

(51 citation statements)

References 60 publications

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“…We found that OECs isolated from HT transgenic animals express the H antigen and exhibit a sevenfold reduction in Galα1,3αGal epitope expression that led to reduced complement activation by human serum, which is consistent with observations on other cell types derived from the HT transgenic pigs (11,12). Although anti-αGal antibody reactivity and complement activation certainly contribute to xenogeneic organ rejection (25,26), cells transplanted into the CNS are also susceptible to humoral-mediated rejection (27). Cicchetti et al (27) showed that an induced anti-αGal antibody response to cells transplanted in the CNS was a parameter for tissue rejection and that the induced anti-αGal response was similar to the response observed in whole organ transplantation, i.e., three-to five-fold increase within the first 2 wk after transplantation.…”

Section: Expression Of the H Antigen On Oecs From Ht Transgenic Pigssupporting

confidence: 88%

Remyelination of the nonhuman primate spinal cord by transplantation of H‐transferase transgenic adult pig olfactory ensheathing cells

Radtke

Akiyama²,

Brokaw

et al. 2003

FASEB j.

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Olfactory ensheathing cells (OECs) have been shown to mediate remyelination and to stimulate axonal regeneration in a number of in vivo rodent spinal cord studies. However, whether OECs display similar properties in the primate model has not been tested so far. In the present study, we thus transplanted highly-purified OECs isolated from transgenic pigs expressing the α1,2 fucosyltransferase gene (H-transferase or HT) gene into a demyelinated lesion of the African green monkey spinal cord. Four weeks posttransplantation, robust remyelination was found in 62.5% of the lesion sites, whereas there was virtually no remyelination in the nontransplanted controls. This together with the immunohistochemical demonstration of the grafted cells within the lesioned area confirmed that remyelination was indeed achieved by OECs. Additional in vitro assays demonstrated 1) that the applied cell suspension consisted of >98% OECs, 2) that the majority of the cells expressed the transgene, and 3) that expression of the HT gene reduced complement activation more than twofold compared with the nontransgenic control. This is the first demonstration that xenotransplantation of characterized OECs into the primate spinal cord results in remyelination.

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Section: Expression Of the H Antigen On Oecs From Ht Transgenic Pigssupporting

confidence: 88%

Remyelination of the nonhuman primate spinal cord by transplantation of H‐transferase transgenic adult pig olfactory ensheathing cells

Radtke

Akiyama²,

Brokaw

et al. 2003

FASEB j.

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“…Thus, the results shown in Figure 1 suggest that while antibodies clearly cause rejection, the process of rejection precedes rather than follows the increase of antibodies in the blood. Moreover, when rejection was averted by expressing human complement regulatory proteins in the xenogeneic source, rather than by depleting antibodies, removal of a functioning transplant led to immediate increase of the level of xenoreactive antibodies in the blood [27]. These experimental observations led us to suggest that graft-specific antibodies might be produced in large amounts but might evade detection in the blood because those antibodies bound to the graft; and, as a corollary, the presence of antibodies may indicate that damage or decrease in blood flow has occurred [28].…”

Section: Accommodation In Experimental Modelsmentioning

confidence: 99%

Accommodation of grafts: Implications for health and disease

Tang

Platt

2007

Human Immunology

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Accommodation refers to the acquired resistance of a graft to immune-mediated injury. It is typically observed after antibodies that would cause rejection of a graft are removed from a recipient and then return. Besides being a condition so induced, accommodation can occur spontaneously, without the depleting of antibodies. Indeed, we postulate that spontaneous accommodation may be the most common outcome of clinical organ transplantation. This communication will review the current understanding of accommodation, emphasizing recent advances and important questions. Among the recent advances are the discoveries of potentially broader relevance of accommodation for biology and immunology and pathways by which accommodation may be achieved. To investigate these pathways and to understand how accommodation begins and how it evolves, clinical organ transplants might offer a useful and incisive model.

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“…Triple drugs (cyclosporine or FK506, azathioprine and prednisolone) and quadruple drugs (ATG, cyclosporine or FK506, azathioprine and prednisolone) treatment in pig transplantation were reported in the literature [27][28][29] . But the optimal dose of immunosuppressive drugs was ascertained in previous reports.…”

Section: Immunosuppressive Treatment Of Auxiliary Lsbt Pigsmentioning

confidence: 99%

“…But the optimal dose of immunosuppressive drugs was ascertained in previous reports. The suggested dose of cyclosporine was from 3 mg/kg·d to 25 mg/ kg·d by IV or SB injection [27,28,30,31] . Some reports indicated that pigs required a higher dose of cyclosporine than humans to prevent allograft rejection in thymus transplantation [32] .…”

Section: Immunosuppressive Treatment Of Auxiliary Lsbt Pigsmentioning

confidence: 99%

Auxiliaryen-blocliver-small bowel transplantation with partial pancreas preservation in pigs

Yin

Ni²,

Jiang³

et al. 2004

WJG

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AIM:The aim of this study was to describe an auxiliary combined liver-small bowel transplantation model with the preservation of duodenum, head of pancreas and hepatic biliary system in pigs. The technique, feasibility, security and immunosuppression were commented. METHODS:Forty outbred long-white pigs were randomized into two groups, and the auxiliary composite liver/small bowel allotransplantations were undertaken in 10 longwhite pigs in each group with the recipient liver preserved. Group A was not treated with immunosuppressive drugs while group B was treated with cyclosporine A and methylprednisolone after operation. The hemodynamic changes and amylase of body fluid (including blood, urine and abdominal drain) were analyzed. RESULTS:The average survival time of the animals was 10±1.929 d (6 to 25 d) in group A while more than 30 d in group B. The pigs could tolerate the hemodynamic fluctuation during operation and the hemodynamic parameters recovered to normal 2 h after blood reperfusion. The transient high amylase level was decreased to normal one week after operation and autopsy showed no pancreatitis. CONCLUSION:Auxiliary en-bloc liver-small bowel transplantation with partial pancreas preservation is a feasible and safe model with simplified surgical techniques for composite liver/small bowel transplantation. This model may be used as a preclinical training model for clinical transplantation method, clinical liver-small bowel transplantation related complication research, basic research including immunosuppressive treatment, organ preservation, acute rejection, chronic rejection, immuno-tolerance and xenotransplantation.

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Humoral Responses to Pig-to-Baboon Cardiac Transplantation: Implications for the Pathogenesis and Treatment of Acute Vascular Rejection and for Accommodation

Cited by 87 publications

References 60 publications

Remyelination of the nonhuman primate spinal cord by transplantation of H‐transferase transgenic adult pig olfactory ensheathing cells

Remyelination of the nonhuman primate spinal cord by transplantation of H‐transferase transgenic adult pig olfactory ensheathing cells

Accommodation of grafts: Implications for health and disease

Auxiliaryen-blocliver-small bowel transplantation with partial pancreas preservation in pigs

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