uu.seUppsala University Publications
Change search
Refine search result
1 - 17 of 17
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 1.
    Asif, Sana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Jonsson, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden..
    Teramura, Yuji
    Univ Tokyo, Dept Bioengn, Tokyo, Japan..
    Gustafson, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Ekdahl, Kristina N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden..
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Conjugation of human recombinant CD39 to primary human hepatocytes protects against thromboinflammation2015In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, S87-S87 p.Article in journal (Other academic)
  • 2.
    Biglarnia, Alireza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Emanuelsson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Quach, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Clausen, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Schneider, Mårten K. J.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    The free radical scavenger S-PBN significantly prolongs DSG-mediated graft survival in experimental xenotransplantation2012In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 19, no 3, 166-176 p.Article in journal (Refereed)
    Abstract [en]

    Background: Nitrones such as 2-sulfo-phenyl-N-tert-butyl nitrone (S-PBN) are known to trap and stabilize free radicals and to reduce inflammation. Recently, S-PBN was shown to reduce infiltration of T lymphocytes and the expression of adhesion molecules on the endothelium in experimental traumatic brain injury. We hypothesized that S-PBN could reduce infiltration of T lymphocytes during cell-mediated xenograft rejection and thereby increase graft survival. The concordant mouse-to-rat heart transplantation model was used to test the hypothesis. In this model, grafts undergo acute humoral xenograft rejection (AHXR) almost invariably on day 3 and succumb to cell-mediated rejection on approximately day 8 if AHXR is inhibited by treatment with 15-deoxyspergualin (DSG). Material and methods: Hearts from Naval Medical Research Institute (NMRI) mice were transplanted to the neck vessels of Lewis rats. Recipients were treated with S-PBN (n = 9), DSG (n = 9), S-PBN and DSG in combination (n = 10) or left untreated (n = 9) for survival studies. S-PBN was given daily intraperitoneally at a dose of 150 mg/kg body weight (BW) on day -1 to 30, and DSG was given daily intraperitoneally at a dose of 10 mg/kg BW on day -1 to 4 and 5 mg/kg BW on day 5 to 21. Nine additional recipients were given S-PBN only on days -1 and 0 in combination with continuous DSG treatment. Grafts were monitored until they stopped beating. Additional recipients were treated with S-PBN (n = 5), DSG (n = 5), S-PBN and DSG in combination (n = 6) or left untreated (n = 5) for morphological, immunohistochemical and flow cytometry analyses on days 2 and 6 after transplantation. Results: S-PBN treatment in combination with DSG resulted in increased median graft survival compared to DSG treatment alone (14 vs. 7 days; P = 0.019). Lower number of T lymphocytes on day 6 (P = 0.019) was observed by ex vivo propagation and flow cytometry when combining S-PBN with DSG, whereas immunohistochemical analyses demonstrated a significant reduction in the number of infiltrated CD4+, but not TCR+, cells. S-PBN treatment alone had no impact on graft survival compared to untreated rats (3 vs. 3 days). No differences were seen in ICAM-1 and VCAM-1 expression or in morphology between the groups. Conclusion: The combination of S-PBN and DSG treatment increases xenograft survival. The main effect of S-PBN appears to be in direct connection with the transplantation. Because of its low toxicity, S-PBN could become useful in combination with other immunosuppressants to reduce cell-mediated xenograft rejection.

  • 3.
    Biglarnia, Alireza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Yamamoto, Shinji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Sedigh, Amir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Drachenberg, Cinthia
    Univ Maryland Hosp, Dept Pathol, Baltimore, MD 21201 USA..
    Wagner, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Sund, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Berglund, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    von Zur-Muehlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Impact of duodenal cuff inflammation on outcome after clinical pancreas transplantation - a survey of a comprehensive follow-up strategy including serial protocol biopsy of the duodenal cuff2015In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, S15-S15 p.Article in journal (Other academic)
  • 4.
    Brandhorst, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Brandhorst, Heide
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Pancreas storage in oxygenated perfluorodecalin does not restore post-transplant function of isolated pig islets pre-damaged by warm ischemia2006In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 13, no 5, 465-470 p.Article in journal (Refereed)
    Abstract [en]

    Background: Cold storage in oxygenated perfluorodecalin (PFD) restores transplant function of ischemically damaged dog pancreata and reduces the impact of cold ischemia on recovery of isolated human islets. Whether PFD storage can improve islet isolation from pancreata exposed to significant warm ischemia (WI) is unclear yet. The present study aimed to clarify this question in adult pigs.

    Methods: After exsanguination, the intestine was removed immediately or left in the cavity for 30 min of WI. Resected pancreata were intraductally flushed with cold University of Wisconsin solution. Subsequently, pancreata were processed immediately by digestion-filtration (group I: 0 min WI, n = 6; II: 30 min WI, n = 6) or first stored for 3 h in oxygenated PFD (III: 0 min WI + PFD, n = 5; IV: 30 min WI + PFD, n = 6).

    Results: Pancreata subjected to 30 min of WI yielded significantly less islets compared with the corresponding non-ischemic organs (I vs. II, P < 0.01; III vs. IV, P < 0.05). Oxygenation did not ameliorate the loss in islet yield (II vs. IV, NS). Ischemic islets were characterized by depleted ATP stores (388 +/- 73 (I) vs. 133 +/- 22 ng/1000 IEQ (II), P < 0.01) and diminished insulin response to glucose calculated as stimulation index (SI; 2.47 +/- 0.36 (I) vs. 0.25 +/- 0.17 (II), P < 0.05). PFD storage of ischemic organs partially restored ATP content (217 +/- 23 ng/1000 IEQ, II vs. IV, P < 0.05) and glucose SI (1.60 +/- 0.09, II vs. IV, P < 0.05) to a significant extent that reached the level of corresponding PFD-stored, non-ischemic pancreata (III vs. IV, NS). Sustained normoglycemia was exclusively observed in diabetic nude mice transplanted with islets isolated from non-ischemic organs. The significantly reduced graft function of ischemic islets (I vs. II, III vs. IV, P < 0.001) was not increased by pancreatic oxygenation (II vs. IV, NS).

    Conclusions: The present study suggests that pancreas short-term storage in oxygenated PFD improves in vitro but not the in vivo function of ischemically damaged pig islets.

  • 5.
    Cooper, David K. C.
    et al.
    Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA..
    Bottino, Rita
    Allegheny Singer Res Inst, Inst Cellular Therapeut, 320 E N Ave, Pittsburgh, PA 15212 USA..
    Gianello, Pierre
    Catholic Univ Louvain, Fac Med, Expt Surg Lab, Brussels, Belgium..
    Graham, Melanie
    Univ Minnesota, Preclin Res Ctr, Dept Surg, St Paul, MN 55108 USA..
    Hawthorne, Wayne J.
    Univ Sydney, Westmead Hosp, Dept Surg, Westmead, NSW 2145, Australia..
    Kirk, Allan D.
    Duke Univ, Sch Med, Dept Surg, Durham, NC USA..
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Park, Chung-Gyu
    Seoul Natl Univ, Dept Microbiol & Immunol, Dept Biomed Sci, Xenotransplantat Res Ctr,Coll Med, Seoul, South Korea..
    Weber, Collin
    Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA..
    First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes - Chapter 4: pre-clinical efficacy and complication data required to justify a clinical trial2016In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 23, no 1, 46-52 p.Article in journal (Refereed)
    Abstract [en]

    In 2009, the International Xenotransplantation Association (IXA) published a consensus document that provided guidelines and recommendations (not regulations) for those contemplating clinical trials of porcine islet transplantation. These guidelines included the IXA's opinion on what constituted rigorous pre-clinical studies using the most relevant animal models and were based on non-human primate testing. We now report our discussion following a careful review of the 2009 guidelines as they relate to pre-clinical testing. In summary, we do not believe there is a need to greatly modify the conclusions and recommendations of the original consensus document. Pre-clinical studies should be sufficiently rigorous to provide optimism that a clinical trial is likely to be safe and has a realistic chance of success, but need not be so demanding that success might only be achieved by very prolonged experimentation, as this would not be in the interests of patients whose quality of life might benefit immensely from a successful islet xenotransplant. We believe these guidelines will be of benefit to both investigators planning a clinical trial and to institutions and regulatory authorities considering a proposal for a clinical trial. In addition, we suggest consideration should be given to establishing an IXA Clinical Trial Advisory Committee that would be available to advise (but not regulate) researchers considering initiating a clinical trial of xenotransplantation.

  • 6.
    Goto, Masafumi
    et al.
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan.;Tohoku Univ, Div Adv Surg Sci & Technol, Sendai, Miyagi 980, Japan..
    Friberg, Andrew
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Ståhle, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Imura, Takehiro
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan..
    Yamagata, Youhei
    Tokyo Univ Agr & Technol, Dept Appl Biol Chem, Tokyo, Japan..
    Watanabe, Kimiko
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan..
    Murayama, Kazutaka
    Tohoku Univ, Div Biomed Measurements & Diagnost, Sendai, Miyagi 980, Japan..
    Inagaki, Akiko
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan..
    Igarashi, Yasuhiro
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan..
    Satomi, Susumu
    Tohoku Univ, Div Adv Surg Sci & Technol, Sendai, Miyagi 980, Japan..
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Proof of concept for the clinical application of animal component free recombinant collagenase for isolating pancreatic islets2015In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, S50-S50 p.Article in journal (Other academic)
  • 7.
    Goto, Masafumi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Tjernberg, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Dufrane, Denis
    Elgue, Graciela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Brandhorst, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Ekdahl, Kristina Nilsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Brandhorst, Heidi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Wennberg, Lars
    Kurokawa, Yoshimochi
    Satomi, Susumu
    Lambris, John D.
    Gianello, Pierre
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Dissecting the instant blood-mediated inflammatory reaction in islet xenotransplantation2008In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 15, no 4, 225-234 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A massive destruction of transplanted tissue occurs immediately following transplantation of pancreatic islets from pig to non-human primates. The detrimental instant blood-mediated inflammatory reaction (IBMIR), triggered by the porcine islets, is a likely explanation for this tissue loss. This reaction may also be responsible for mediating an adaptive immune response in the recipient that requires a heavy immunosuppressive regimen. MATERIALS AND METHODS: Low molecular weight dextran sulfate (LMW-DS) and the complement inhibitor Compstatin were used in a combination of in vitro and in vivo studies designed to dissect the xenogeneic IBMIR in a non-human primate model of pancreatic islet transplantation. Adult porcine islets (10,000 IEQs/kg) were transplanted intraportally into three pairs of cynomolgus monkeys that had been treated with LMW-DS or heparin (control), and the effects on the IBMIR were characterized. Porcine islets were also incubated in human blood plasma in vitro to assess complement inhibition by LMW-DS and Compstatin. RESULTS: Morphological scoring and immunohistochemical staining revealed that the severe islet destruction and macrophage, neutrophilic granulocyte, and T-cell infiltration observed in the control (heparin-treated) animals were abrogated in the LMW-DS-treated monkeys. Both coagulation and complement activation were significantly reduced in monkeys treated with LMW-DS, but IgM and complement fragments were still found on the islet surface. This residual complement activation could be inhibited by Compstatin in vitro. CONCLUSIONS: The xenogeneic IBMIR in this non-human primate model is characterized by an immediate binding of antibodies that triggers deleterious complement activation and a subsequent clotting reaction that leads to further complement activation. The effectiveness of LMW-DS (in vivo and in vitro) and Compstatin (in vitro) in inhibiting this IBMIR provides the basis for a protocol that can be used to abrogate the IBMIR in pig-human clinical islet transplantation.

  • 8.
    Grapensparr, Liza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Intracardially injected neural crest stem cells home to the pancreas and delays disease progression in an animal model for type 1 diabetes2015In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, S198-S199 p.Article in journal (Other academic)
  • 9. Groth, Carl G
    et al.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Proceedings of "Pig-to-Man Islet Transplant Summit" held at the Nobel Forum, Stockholm, June 4-5, 20072008In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 15, no 2, 77-78 p.Article, review/survey (Other academic)
  • 10.
    Hårdstedt, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Finnegan, Colleen P
    Kirchhof, Nicole
    Hyland, Kendra A
    Wijkstrom, Martin
    Murtaugh, Michael P
    Hering, Bernhard J
    Post-transplant upregulation of chemokine messenger RNA in non-human primate recipients of intraportal pig islet xenografts2005In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 12, no 4, 293-302 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    We have previously shown that pig-to-primate intraportal islet xenografts reverse diabetes, escape hyperacute rejection, and undergo acute cellular rejection in non-immunosuppressed recipients. To gain a better understanding of mechanisms contributing to xenoislet rejection in non-human primates we examined gene expression in livers bearing islet xenografts in the first 72 h after transplantation.

    METHODS:

    Liver specimens were collected at sacrifice from seven non-immunosuppressed rhesus macaques at 12, 24, 48 and 72 h after intraportal porcine islet transplantation. Following total RNA extraction, mRNA was quantified using SYBR green real-time reverse transcription polymerase chain reaction (RT-PCR) for species-specific immune response genes. Data were analyzed using comparative cycle threshold (Ct) analysis, adjusted for specific primer-efficiencies and normalized to cyclophilin expression.

    RESULTS:

    Porcine insulin mRNA was detected in all liver samples. Cluster analysis revealed differential gene expression patterns at 12 and 24 h (early) compared with at 48 and 72 h (late) post-transplant. Gene expression patterns were associated with histological findings of predominantly neutrophils and only a few lymphocytes at 12 and 24 h and an increasing number of lymphocytes and macrophages at 48 and 72 h. Transcript levels of CXCR3 and its ligands, interferon-inducible protein 10 (IP-10) and monokine induced by IFN-gamma (Mig), significantly increased between early and late time points together with expression of MIP-1alpha, regulated on activation normal T expressed and secreted protein (RANTES) and MCP-1. CCR5 showed only a marginal, non-significant increase. Fas ligand, perforin and granzyme B transcripts were all elevated at 48 and 72 h post-transplant.

    CONCLUSIONS:

    Our data suggest that CXCR3, with ligands IP-10 and Mig, is involved in T cell recruitment in acute islet xenograft rejection in non-human primates. Upregulation of RANTES and MIP-1alpha transcripts in the absence of a significant CCR5 increase suggests a possible involvement of other chemokine receptors. MCP-1 expression is associated with T cell and macrophage infiltration. Elevated cytotoxic effector molecule expression (Fas ligand, perforin, granzyme B) indicates T-cell mediated graft destruction by cytotoxic and cytolytic mechanisms within 48 to 72 h after transplantation. These results identify the CXCR3-mediated chemoattractant pathway as an immunosuppressive target in pig-to-primate islet xenotransplantation.

  • 11.
    Korsgren, Olle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Groth, Carl G
    Co-transplantation of human and pig islets2008In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 15, no 2, 112-112 p.Article, review/survey (Refereed)
  • 12.
    Lorant, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Krook, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Wilton, Jacob
    Olausson, Michael
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Johnsson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Intragraft cytokine mRNA expression in rejecting and non-rejecting Vascularised Xenografts2003In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 10, no 4, 311-324 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The aim of the present study was to further investigate the characteristics of both graft-infiltrating cells and splenocytes during acute vascular rejection (AVR), cell-mediated rejection and non-rejection of vascularized concordant xenografts, by analysing both proinflammatory [interleukin-1beta (IL-1beta) and tumour necrosis factor (TNF-alpha)] and more specific [(IL-2, IL-4, IL-10, IL-12p40 and interferon-gamma (IFN-gamma)] cytokines. A parallel investigation was made of the antibody response of IgM and IgG to the xenografts.

    METHODS:

    Mouse hearts were heterotopically transplanted to the neck vessels of recipient rats. Grafts, spleens and sera were collected from untreated (AVR) and cyclosporin A (CyA) treated animals on day 2 after transplantation. Organs from rats treated with 15-deoxyspergualin (DSG) or CyA and DSG in combination were harvested on both day 2 and day 8. Grafts from DSG-treated rats undergo cell-mediated rejection and stop beating on day 9 and forth, while CyA + DSG treatment results in long-term graft survival. Real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was applied for analysis of intragraft and splenic cytokine messenger RNA (mRNA) expression. The phenotypes of the graft infiltrating cells were characterized by immunohistochemistry. The antibody response was investigated by means of immunofluorescence, haemagglutination and flow cytometry.

    RESULTS:

    All the studied cytokines (IL-1beta, IL-2, IL-4, IL-10, IL-12p40, IFN-gamma and TNF-alpha) were up-regulated in the grafts from rejecting untreated (day 2) and DSG-treated animals (day 8) in comparison with grafts from CyA + DSG treated animals (day 8). On day 2 under immunosuppression with CyA, DSG or CyA + DSG no or low cytokine mRNA levels were found. The mRNA levels of IL-2, IL-4 and IFN-gamma in the spleens were suppressed under both DSG- and CyA + DSG treatment on day 8. Immunofluorescence showed deposits of both IgM and IgG in grafts from untreated, CyA-treated (day 2) and DSG-treated (day 8) animals, while CyA + DSG treatment diminished these deposits on both day 2 and day 8. No circulating antibodies were identified in either group.

    CONCLUSION:

    We hereby conclude that both AVR on day 2 and cell-mediated rejection on day 8 (under DSG treatment) in a concordant cardiac mouse-to-rat xenotransplantation model are associated with an increase of proinflammatory cytokines, T helper 1 (Th1)-associated cytokines as well as IL-10, while immunosuppression with CyA + DSG diminishes the levels of all examined cytokines. Grafts undergoing AVR or cellular rejection are subjected to deposits of both IgM and IgG, although circulating donor specific antibodies are undetectable in serum.

  • 13.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    The instant blood-mediated inflammatory reaction in xenogeneic islet transplantation2008In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 15, no 2, 96-98 p.Article, review/survey (Refereed)
  • 14.
    Schmidt, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Forsman, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Andersson, Göran
    Blomberg, Jonas
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Pig islet xenotransplantation: activation of porcine endogenous retrovirus in the immediate post-transplantation period2005In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 12, no 6, 450-456 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Porcine endogenous retroviruses (PERV) are considered as the main infectious barrier in islet xenotransplantation. PERV has been shown to infect, but not to cause symptomatic disease in mice after islet transplantation. In vivo activation of PERV have so far not been examined. Expression of PERV was examined in adult and fetal porcine islets with or without the presence of known retroviral inducers or after transplantation to rats.

    METHODS: Isolated adult and fetal porcine islets were cultured under normal conditions or in the presence of dexamethasone or 5-azacytidine and 5-iodo-2-deoxyuridine. PERV mRNA content was analyzed by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and culture supernatants were analyzed for the presence of retroviral RT. Also, fetal islets were transplanted under the kidney capsule of immunocompetent or nude athymic rats. Expression of PERV mRNA in the grafts was evaluated by real-time quantitative RT-PCR. Infiltration of immunocompetent cells were evaluated by immunohistochemistry.

    RESULTS: Both fetal and adult islets in culture produced small or even undetectable amounts of PERV mRNA and retroviral RT. PERV expression was not enhanced by retroviral inducers. In contrast, activation of PERV expression was observed the first day after transplantation of fetal islet-like cell clusters in both athymic and normal rats. PERV expression peaked after 1 to 3 days and was then rapidly returned to background levels. PERV expression neither correlated with the innate immune response seen in athymic rats nor with the specific process of rejection in normal rats.

    CONCLUSION: Both fetal and adult islets produce low amounts of PERV mRNA in culture. After transplantation PERV expression is induced, seemingly independent of both the unspecific inflammatory response and the specific T-cell-mediated rejection process. It is speculated that PERV expression is correlated with the level of hypoxia in the islet xenograft.

  • 15.
    Schmidt, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Krook, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Goto, Masafumi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    MyD88-dependent toll-like receptor signalling is not a requirement for fetal islet xenograft rejection in mice2004In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 11, no 4, 347-352 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Rejection of pancreatic islet xenografts in mice shares immunopathological features with a Th1-associated delayed-type hypersensitivity (DTH) reaction. The aim of the present study was to investigate the mechanism of acute cellular xenograft rejection in a strain of mice with a targeted gene disruption of the toll-like receptor (TLR) signal adaptor protein MyD88. These mice have been shown to have markedly impaired Th1 immunity.

    METHODS: The MyD88-/- and normal mice were transplanted with 2 microl of fetal porcine islet-like cell clusters (ICC) under the left kidney capsule. On days 3, 6 or 12 after transplantation the mice were killed and the grafts either prepared for immunohistochemistry or real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The number of remaining ICC and infiltrating cells with different phenotypic characteristics was assessed semi-quantitatively. Grafts used for quantitative RT-PCR were analysed for content of murine mRNA of interferon (IFN)-gamma, interleukin (IL)-12p40, IL-4 and IL-10.

    RESULTS: On day 3, the rejection process was initiated in both MyD88-/- and normal mice as characterized by a moderate infiltration of F4/80+ and MAC-1+ macrophages and occasional CD3+ and CD4+ cells. Expression of IFN-gamma and IL-12p40 was lower but still detectable in the MyD88-/- mice, when compared with control animals. By day 6, rejection was almost completed in all animals with only few ICC remaining. 12 days after transplantation all grafts were completely destroyed and heavily infiltrated by macrophages. Moderate numbers of CD3+ and CD4+ and occasional CD8+ cells were also present.

    CONCLUSIONS: Islet xenograft rejection was found to persist in MyD88-/- mice. Despite a relatively lower expression of the Th1-associated cytokines IFN-gamma and IL12-p40 within the xenograft area, both the time course and morphological pattern of the rejection were essentially similar to that found in normal animals. Hence, MyD88-dependent TLR signalling does not appear to be a crucial component of acute cellular xenograft rejection

  • 16.
    Teramura, Yuji
    et al.
    Univ Tokyo, Dept Bioengn, Tokyo, Japan..
    Asif, Sana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Gustafson, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Nilsson-Ekdahl, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden..
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Heparinzation of cell surfaces with a heparin-binding peptide-conjugated PEG-lipid for regulation of thromboinflammation in transplantation of human MSC and hepatocyte2015In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, S70-S70 p.Article in journal (Other academic)
  • 17.
    Ullsten, Sara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Grapensparr, Liza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sandberg, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Schwann cells regulate angiogenesis and blood vessel structure in native and transplanted pancreatic2015In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, S46-S46 p.Article in journal (Other academic)
1 - 17 of 17
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf