Role of Complement Regulatory Proteins in the Survival of Murine Allo-transplanted Sertoli Cells

Sertoli cells (SC) are known to contain immunoprotective properties, which allow them to survive as allografts without the use of immunosuppressive drugs. Experiments were designed to determine which factors are related to prolonged survival of allogeneic SC. Balb/c derived Sertoli (TM4) and colon cancer (CT-26) cell lines were implanted beneath the kidney capsule of non-immunosuppressed C57BL/6 mice and compared their survival as allografts. Compared to TM4 graft, which survived more than 7 days after transplantation, CT-26 showed massive infiltration of polymorphonuclear cells, necrosis and enlargement of draining lymph nodes. Cultured cell lines showed no differences in their expression patterns of FasL, TGF β1, clusterin and two complement regulatory proteins (CRP, i.e., membrane cofactor protein, MCP; decay accelerating factor, DAF), but protectin (CD59), another member of CRP was expressed only on TM4. These results suggest that CD59 and unknown factors may contribute to the prolonged survival of SC in non-immunoprivileged sites

Mechanism of Humoral and Cellular Immune Modulation Provided by Porcine Sertoli Cells

The understanding of main mechanisms that determine the ability of immune privilege related to Sertoli cells (SCs) will provide clues for promoting a local tolerogenic environment. In this study, we evaluated the property of humoral and cellular immune response modulation provided by porcine SCs. Porcine SCs were resistant to human antibody and complement-mediated formation of the membrane attack complex (38.41±2.77% vs. 55.02±5.44%, p=0.027) and cell lysis (42.95±1.75% vs. 87.99±2.25%, p<0.001) compared to immortalized aortic endothelial cells, suggesting that porcine SCs are able to escape cellular lysis associated with complement activation by producing one or more immunoprotective factors that may be capable of inhibiting membrane attack complex formation. On the other hand, porcine SCs and their culture supernatant suppressed the up-regulation of CD40 expression (p<0.05) on DCs in the presence of LPS stimulation. These novel findings, as we know, suggest that immune modulatory effects of porcine SCs in the presence of other antigen can be obtained from the first step of antigen presentation. These might open optimistic perspectives for the use of porcine SCs in tolerance induction eliminating the need for chronic immunosuppressive drugs

The Effect of Cyclooxygenase-2 Expression on Tumor Volume Response in Patients Treated with Radiotherapy for Uterine Cervical Cancer

We investigated the correlation between Cyclooxygenase-2 (COX-2) expression and the tumor response in patients with cervical cancer that were treated with curative radiotherapy (RT). Fifty-seven patients with squamous cell carcinoma were treated with concurrent radiochemotherapy (CRCT, n=29) or RT alone (n=28). The response of each patient was evaluated by three serial Magnetic Resonance Imaging examinations: before the start of RT, at four weeks after the start of RT (mid-RT) and at four weeks after the completion of RT (post-RT). Forty-three patients had positive COX-2 expression. The COX-2 negative patients achieved a higher rate of complete response (CR) at mid-RT than did the COX-2 positive patients (28.6% vs. 7.0%, P=0.054), but not at post-RT (64.3% vs. 69.8%). The initial tumor volume was a significant predictor of CR at mid-RT (P=0.003) and post-RT (P=0.004). The multivariate analysis showed that the initial tumor volume (at mid-RT and post-RT) and CRCT (at post-RT) were significant predictors of CR; however, the COX-2 expression was not. In conclusion, the COX-2 expression status has no significant correlation with the tumor response. Further studies on the changes in COX-2 expression levels during RT may be helpful for determination of its role in the tumor response to treatment and patient prognosis

Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage

The International Stem Cell Initiative analyzed 125 human embryonic stem (ES) cell lines and 11 induced pluripotent stem (iPS) cell lines, from 38 laboratories worldwide, for genetic changes occurring during culture. Most lines were analyzed at an early and late passage. Single-nucleotide polymorphism (SNP) analysis revealed that they included representatives of most major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed haphazardly with no link to time in culture. Structural variants, determined from the SNP arrays, also appeared sporadically. No common variants related to culture were observed on chromosomes 1, 12 and 17, but a minimal amplicon in chromosome 20q11.21, including three genes expressed in human ES cells, ID1, BCL2L1 and HM13, occurred in >20% of the lines. Of these genes, BCL2L1 is a strong candidate for driving culture adaptation of ES cells

Sensitivity of the Keum River basin to climate change

This study reports an examination of the sensitivity of water resources in the Keum River basin to climate change. Assuming a doubling in CO2 concentrations, a cooperative study provided four climate change scenarios for this study, which have been translated into temperature and precipitation scenarios on a basin scale. The study utilized these temperature and precipitation data for each climate change scenario as inputs to the NWS-PC model to generate the corresponding streamflow scenario over the Keum River basin. A reservoir simulation model for the Dae-Chung Dam in the Keum River basin has been developed with an object-oriented simulation environment, STELLA. For each streamflow scenario, the performance of the reservoir was assessed in terms of reliability, resiliency, and vulnerability. Although the simulation results are heavily dependent on the choice of the climate change scenarios, the following conclusions can be clearly concluded: (1) the future streamflow over the Dae-Chung Dam tends to decease during the dry period, which seriously increases competitive water use issues and (2) flood control issues predominate under the 2CO2-High case

Establishment and characterization of porcine Sertoli cell line for the study of xenotransplantation

BACKGROUND: An understanding of the main mechanism that determines the ability of immune privilege related to Sertoli cells (SC) will provide clues for promoting a local tolerogenic environment. In this report, we established neonatal porcine SC line and evaluated their characteristics. METHODS: SC line was established following the transfection of primary SC (NPSC) from the testis of neonatal pig with plasmid pRNS-1 carrying genes for neomycin resistance and the SV40 large T antigen. Immunohistochemistry and RT-PCR were performed to evaluate the character of immortalized SC lines. RESULTS: Our immortalized SC line (iPS) proliferated stably and had a phenotype similar to NPSC, as indicated by the immunoexpression of follicle stimulating hormone receptor (FSHR), and mRNA expression of androgen receptor (AR), and Wilms' tumor antigen (WT1). Interestingly, NPSC and iPS expressed mRNA of complement regulatory proteins (CRP) such as membrane cofactor protein (CD46), decay accelerating factor (DAF or CD55), and protectin (CD59), but CD59 mRNA expression was negligible in iPS. CONCLUSION: These results suggest that iPS, immortalized by the introduction of SV40 T, retain their original characteristics, except for the relatively low expression of CD59, and that they may be useful for future in vitro and in vivo studies of immune privilege mechanisms related to SC