فهرست مطالب

Organ Transplantation Medicine - Volume:6 Issue: 2, Spring 2015

International Journal of Organ Transplantation Medicine
Volume:6 Issue: 2, Spring 2015

  • تاریخ انتشار: 1394/01/19
  • تعداد عناوین: 6
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  • Mh Karimi, B. Geramizadeh, Sa Malek, Hosseini Page 45
    Liver is an exclusive anatomical and immunological organ that displays a considerable tolerance effect. Liver allograft acceptance is shown to occur spontaneously within different species. Although in human transplant patients tolerance is rarely seen, the severity level and cellular mechanisms of transplant rejection vary. Non-paranchymal liver cells, including Kupffer cells, liver sinusoidal endothelial cells, hepatic stellate cells, and resident dendritic cells may participate in liver tolerogenicity. The mentioned cells secret anti-inflammatory cytokines such as TGF-β and IL-10 and express negative co-stimulatory molecules like PD-L1 to mediate immunosuppression. Other mechanisms such as microchimerism, soluble major histocompatibility complex and regulatory T cells may take part in tolerance induction. Understanding the mechanisms involved in liver transplant rejection/tolerance helps us to improve therapeutic options to induce hepatic tolerance.
  • B. Rajeshkumar, P. Agrawal, M. Rashighi, Rf Saidi Page 55
    Background
    Organ transplantation currently requires long-term immunosuppression. This is associated with multiple complications including infection, malignancy and other toxicities. Immunologic tolerance is considered the optimal solution to these limitations.
    Objective
    To develop a simple and non-toxic regimen to induce mixed chimerism and tolerance using mesenchymal stem cell (MSC) in a murine model.
    Methods
    Wild type C57BL6 (H2Dk) and Bal/C (H2Dd) mice were used as donors and recipients, respectively. We studied to achieve tolerance to skin grafts (SG) through mixed chimerism (MC) by simultaneous skin graft and non-myeloablative donor bone marrow transplantation (DBMT) +/– MSC. All recipients received rapamycin and CTLA-4 Ig without radiation.
    Results
    DBMT+MSC combined with co-stimulation blockage and rapamycin led to stable mixed chimerism, expansion of Tregs population and donor-specific skin graft tolerance. The flow cytometry analysis revealed that recipient mice developed 15%–85% chimerism. The skin allografts survived for a long time. Elimination of MSC failed to induce mixed chimerism and tolerance.
    Conclusion
    Our results demonstrate that donor-specific immune tolerance can be effectively induced by non-myeloablative DBMT-MSC combination without any additional cytoreductive treatment. This approach provides a promising and non-toxic allograft tolerance strategy.
  • M. Bahrebar, M. Soleimani, Mh Karimi, A. Vahdati, R. Yaghobi Page 61
    Background
    Pancreatic duodenal homeobox1 (PDX-1) is a transcription factor that is important in regulating pancreas development and maintaining β-cell function. β-cell replacement is an effective approach for the treatment of type 1 diabetes. Human adipose-mesenchymal stem cells (hAMSCs) are the ideal population cells for differentiating into insulin-producing cells.
    Objective
    To determine if islet-like cell aggregates production could be generated from hAMSCs by lentiviral overexpression of PDX-1.
    Methods
    After isolation of hAMSCs, characteristics of these cells were identified by flow-cytometic analysis and multilineage differentiation studies. PDX-1 gene delivered into hAMSCs through lentiviral vector for differentiating hAMSCs into insulin-producing cells (IPCs) at the utilized protocol for 14 days. Characteristics of IPCs were evaluated by immunocytofluorescence, dithizone staining, and quantitative reverse transcription PCR. In response to high glucose medium, insulin release was detected by chemiluminescence enzyme immunoassay.
    Results
    The islet-like cell aggregates appeared about 10 days after introduction of PDX-1 into hAMSCs. PDX-1 induced its own expression (auto-induction), a number of islet-related genes such as Ngn3, Nkx2- 2, and insulin. The insulin-positive cells were detected in the PDX-1 transduced cells. In response to glucose challenge test, secretion of insulin hormone in the medium with high glucose concentration significantly increased in the PDX-1-transduced cells related to medium with low glucose concentration.
    Conclusion
    Introduction of lentiviral PDX-1 significantly induces hAMSCs to differentiate into islet-like cell aggregates, which may provide a source of adipose stem cells-derived insulin-producing cells for cell replacement therapy in type 1 diabetes.
  • M. Pakfetrat, R. Yaghobi, Z. Salmanpoor, J. Roozbeh, S. Torabinezhad, S. Kadkhodaei Page 77
    Background
    Polyomavirus BK is a major cause of nephropathy in immunosuppressed transplanted patients. Non-invasive diagnostic protocols such as molecular detection of polyomavirus BK replication are a useful strategy to predict BK virus-associated nephropathy (BKVAN).
    Objective
    To determine the prevalence of polyomavirus BK infection among kidney transplant patients suspected to have BKVAN.
    Methods
    In a cross-sectional study 108 kidney transplanted patients whose laboratory and clinical presentation were in favor of nephropathy between 2010 and 2012, were enrolled for analysis. Polyomavirus BK replication was evaluated in plasma and tissue samples of studied patients using a quantitative realtime PCR. Active cytomegalovirus infection was analyzed in studied patients using antigenemia method. A possible association between polyomavirus BK infection with clinical and laboratory risk factors of BKVAN were evaluated.
    Results
    The polyomavirus BK replication was found in 17 (15.7%) of 108 of plasma and 9 (11%) of 82 tissue samples in kidney transplanted patients. Cytomegalovirus co-infection was found in 3 of 17 and 3 of 9 plasma and tissue samples in polyomavirus BK infected patients, respectively. Significant associations were found between polyomavirus BK infection with tubulointerstitial nephritis and acute cellular rejection, as important pathologic findings of BKVAN.
    Conclusion
    Diagnosis of single and co-infection of polyomavirus BK infection in plasma samples is a useful assay to evaluate the risk of BKVAN in kidney transplant patients. Established threshold values for studied viral infections have beneficial use in screening of kidney transplant patients at risk of BKVAN, need to confirm and standardized in completed further studies.
  • Mustafa Ascha, Mona Ascha, Nn Zein, N. Alkhouri, B. Eghtesad, K. Abu, Elmagd, T. Diago, Ia Hanouneh Page 86
    Hepatitis C virus (HCV) infection remains a leading indication for orthotopic liver transplantation (OLT) worldwide. Recurrence of HCV following OLT is universal. There is scarcity of data on the post-OLT treatment of HCV genotype-4—the predominant genotype in North Africa and the Middle East. Herein, we present three patients who have experienced HCV genotype-4 recurrence post-OLT. All three patients were interferon-naive and were treated with simeprivir (SIM) and sofosbuvir (SOF) combination therapy for 12–24 weeks. The data from this case series show that SIM+SOF are well-tolerated and effective for achieving viral clearance in HCV genotype-4 post-OLT patients. Given the limited nature of a case series, further research must be pursued regarding post-OLT HCV genotype-4 responses to direct-acting anti-viral therapy.