Tianjin General Surgery Institute

Tianjin, China

Tianjin General Surgery Institute

Tianjin, China

Time filter

Source Type

Lu N.,Tianjin General Surgery Institute | Zhou D.,Nanchong Central Hospital | Li W.,Tianjin General Surgery Institute | He X.,Tianjin General Surgery Institute | Zhu L.,Tianjin General Surgery Institute
Gene Therapy and Molecular Biology | Year: 2012

Liver metastases are common for colon cancer and associate with poor prognosis. Interleukin-15 is considered to be one of the most promising cytokine for cancer gene therapy based on its activity on both innate and adaptive immunity. This study investigated the effect of IL-15 immune gene therapy on metastatic liver disease of colon cancer in murine model. IL-15 overexpression plasmid vector was transfected into CT-26 cells in vitro by lipofection and into mice in vivo by intravenous injection. IL-15 expression was detected by ELISA. The impact of IL-15 on T cell subsets were analyzed by flow cytometry. Murine model of CT-26 colon cancer liver metastases were established and the effect of IL-15 gene therapy on liver metastasis of colon cancer were determined. Results showed that IL-15 was detected in the supernatant of IL-15-overexpression plasmid transfected mouse CT-26 cells. Transgene expression was observed in the liver tissue after intravenous injection of IL-15-overexpression plasmid. IL-15 expression in vivo increased the proportion of CD3+CD8+ cells in peripheral blood of mice. Decreased liver metastases indicated by liver weight were observed in IL-15 gene therapy group. The survival time of mice in IL-15 gene therapy group is also significantly prolonged. In conclusion, IL-15 gene therapy inhibits experimental colon cancer liver metastases, prolongs the survival of tumor-bearing mice. IL-15 gene therapy provides a new approach for the treatment of colorectal liver metastases and is worth further evaluation.


Lu S.,Tianjin Medical University | Lu S.,Tianjin General Surgery Institute | Shi G.,Tianjin Medical University | Shi G.,Tianjin General Surgery Institute | And 14 more authors.
Journal of Translational Medicine | Year: 2016

Background: The endometrial regenerative cell (ERC) is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl4)-induced acute liver injury (ALI). Methods: An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl4. Transplanted ERCs were intravenously injected (1 million/mouse) into mice 30 min after ALI induction. Liver function, pathological and immunohistological changes, cell tracking, immune cell populations and cytokine profiles were assessed 24 h after the CCl4 induction. Results: ERC treatment effectively decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and improved hepatic histopathological abnormalities compared to the untreated ALI group. Immunohistochemical staining showed that over-expression of lymphocyte antigen 6 complex, locus G (Ly6G) was markedly inhibited, whereas expression of proliferating cell nuclear antigen (PCNA) was increased after ERC treatment. Furthermore, the frequency of CD4+ and CD8+ T cell populations in the spleen was significantly down-regulated, while the percentage of splenic CD4+CD25+FOXP3+ regulatory T cells (Tregs) was obviously up-regulated after ERC treatment. Moreover, splenic dendritic cells in ERC-treated mice exhibited dramatically decreased MHC-II expression. Cell tracking studies showed that transplanted PKH26-labeled ERCs engrafted to lung, spleen and injured liver. Compared to untreated controls, mice treated with ERCs had lower levels of IL-1β, IL-6, and TNF-α but higher level of IL-10 in both serum and liver. Conclusions: Human ERCs protect the liver from acute injury in mice through hepatocyte proliferation promotion, as well as through anti-inflammatory and immunoregulatory effects. © 2016 The Author(s).


Lv Y.,Tianjin Medical University | Xu X.,Tianjin General Surgery Institute | Zhang B.,Tianjin Medical University | Zhou G.,Tianjin General Surgery Institute | And 6 more authors.
Journal of Translational Medicine | Year: 2014

Endometrial regenerative cells (ERCs) are mesenchymal-like stem cells that can be non-invasively obtained from menstrual blood and are easily grown /generated at a large scale without tumorigenesis. We previously reported that ERCs exhibit unique immunoregulatory properties in vitro, however their immunosuppressive potential in protecting the colon from colitis has not been investigated. The present study was undertaken to determine the efficacy of ERCs in mediating immunomodulatory functions against colitis. Methods: Colitis was induced by 4% dextran-sulfate-sodium (DSS, in drinking water) in BALB/c mice for 7 days. ERCs were cultured from healthy female menstrual blood, and injected (1 million/mouse/day, i.v.) into mice on days 2, 5, and 8 following colitis induction. Colonic and splenic tissues were collected on day 14 post-DSS-induction. Clinical signs, disease activity index (DAI), pathological and immunohistological changes, cytokine profiles and cell populations were evaluated. Results: DSS-induced mice in untreated group developed severe colitis, characterized by body-weight loss, bloody stool, diarrhea, mucosal ulceration and colon shortening, as well as pathological changes of intra-colon cell infiltrations of neutrophils and Mac-1 positive cells. Notably, ERCs attenuated colitis with significantly reduced DAI, decreased levels of intra-colon IL-2 and TNF-Α, but increased expressions of IL-4 and IL-10. Compared with those of untreated colitis mice, splenic dendritic cells isolated from ERC-treated mice exhibited significantly decreased MHC-II expression. ERC-treated mice also demonstrated much less CD3+CD25+ active T cell and CD3+CD8+ T cell population and significantly higher level of CD4+CD25+Foxp3+ Treg cells. Conclusions: This study demonstrated novel anti-inflammatory and immunosuppressive effects of ERCs in attenuating colitis in mice, and suggested that the unique features of ERCs make them a promising therapeutic tool for the treatment of ulcerative colitis. © Lv et al. licensee BioMed Central Ltd.


Sun P.,Tianjin Medical University | Sun P.,Tianjin General Surgery Institute | Liu J.,Tianjin Medical University | Li W.,Tianjin Medical University | And 9 more authors.
Journal of Translational Medicine | Year: 2016

Background: Endometrial regenerative cells (ERCs) is an attractive novel type of adult mesenchymal stem cells that can be non-invasively obtained from menstrual blood and are easily replicated at a large scale without tumorigenesis. We have previously reported that ERCs exhibit unique immunoregulatory properties in experimental studies in vitro and in vivo. In this study, the protective effects of ERCs on renal ischemia-reperfusion injury (IRI) were examined. Methods: Renal IRI in C57BL/6 mice was induced by clipping bilateral renal pedicles for 30min, followed by reperfusion for 48h. ERCs were isolated from healthy female menstrual blood, and were injected (1 million/mouse, i.v.) into mice 2h prior to IRI induction. Renal function, pathological and immunohistological changes, cell populations and cytokine profiles were evaluated after 48h of renal reperfusion. Results: Here, we showed that as compared to untreated controls, administration of ERCs effectively prevented renal damage after IRI, indicated by better renal function and less pathological changes, which were associated with increased serum levels of IL-4, but decreased levels of TNF-aα, IFN-γ and IL-6. Also, ERC-treated mice displayed significantly less splenic and renal CD4+ and CD8+ T cell populations, while the percentage of splenic CD4+CD25+ regulatory T cells and infiltrating M2 macrophages in the kidneys were significantly increased in ERC-treated mice. Conclusions: This study demonstrates that the novel anti-inflammatory and immunoregulatory effects of ERCs are associated with attenuation of renal IRI, suggesting that the unique features of ERCs may make them a promising candidate for cell therapies in the treatment of ischemic acute kidney injury in patients. © 2016 Sun et al.


Wang H.,Tianjin Medical University | Wang H.,Tianjin General Surgery Institute | Qi F.,Tianjin Medical University | Dai X.,Tianjin Medical University | And 9 more authors.
Transplant Immunology | Year: 2014

Background: The potential of mesenchymal stem cells (MSCs) for immunosuppression has been tested in transplantation, but its mechanisms are not fully understood. This study investigated the role of MSC-expressing B7-H1 in the induction of immune tolerance to cardiac allografts by the combination therapy of MSCs and rapamycin (RAPA). Methods: The anti-alloimmunity of donor MSCs in the presence or absence of RAPA was examined in both mouse cardiac allograft model (C57BL/6 to BALB/c mice) and a variety of cultured immune cells. Immunohistochemical staining was used for the measurement of intragraft antibody deposition, and fluorescence-activated cell sorting (FACS) for the determination of serum alloantibodies and leukocyte phenotypes. Results: B7-H1 expression in cultured MSCs was up-regulated following IFN-γ stimulation. In transplant recipients, combination therapy of MSCs and RAPA induced immune tolerance to allografts, but blockade of B7-H1 on MSCs with monoclonal antibody abrogated the combination therapy-induced immune tolerance as heart allografts were rejected. The negative effect of MSC-expressing B7-H1 neutralization on graft survival was correlated with a reduction of regulatory immune cells (CD4+CD25+Foxp3+ T cells, tolerogenic dendritic cells and IL-4highIL-10HighCD83low B cells), and also with an increase in alloantibody (IgG and IgM) levels both inside the grafts and in the circulation as compared with un-neutralized controls. In vitro MSC-mediated suppression of antibody production and B cell proliferation depended on B7-H1 function and cell contact between CD19+ B cells and MSCs. Conclusion: These data suggest that MSC-expressing B7-H1 mediates the immune tolerance to cardiac allografts in recipients receiving MSC and RAPA combination therapy. © 2014 Elsevier B.V.


Tian W.,Tianjin Medical University | Liu Y.,Tianjin Medical University | Zhang B.,Tianjin Medical University | Dai X.,Tianjin Medical University | And 8 more authors.
Lung | Year: 2015

Background: Cold ischemia-reperfusion injury (IRI) is a major cause of graft failure in lung transplantation. Despite therapeutic benefits of mesenchymal stem cells (MSCs) in attenuating acute lung injury, their protection of lung transplants from cold IRI remains elusive. The present study was to test the efficacy of MSCs in the prevention of cold IRI using a novel murine model of orthotopic lung transplantation. Methods: Donor lungs from C57BL/6 mice were exposed to 6 h of cold ischemia before transplanted to syngeneic recipients. MSCs were isolated from the bone marrows of C57BL/6 mice for recipient treatment. Gas exchange was determined by the measurement of blood oxygenation, and lung injury and inflammation were assessed by histological analyses. Results: Intravenously delivered MSC migration/trafficking to the lung grafts occurred within 4-hours post-transplantation. As compared to untreated controls, the graft arterial blood oxygenation (PaO2/FiO2) capacity was significantly improved in MSC-treated recipients as early as 4 h post-reperfusion and such improvement continued over time. By 72 h, oxygenation reached normal level that was not seen in controls. MSCs treatment conferred significant protection of the grafts from cold IRI and cell apoptosis, which is correlated with less cellular infiltration, a decrease in proinflammatory cytokines (TNF-α, IL-6) and toll-like receptor 4, and an increase in anti-inflammatory TSG-6 generation. Conclusions: MSCs provide significant protection against cold IRI in lung transplants, and thus may be a promising strategy to improve outcomes after lung transplantation. © 2014, Springer Science+Business Media New York.


PubMed | University of British Columbia, Tianjin General Surgery Institute and Tianjin Medical University
Type: | Journal: Journal of translational medicine | Year: 2016

Endometrial regenerative cells (ERCs) is an attractive novel type of adult mesenchymal stem cells that can be non-invasively obtained from menstrual blood and are easily replicated at a large scale without tumorigenesis. We have previously reported that ERCs exhibit unique immunoregulatory properties in experimental studies in vitro and in vivo. In this study, the protective effects of ERCs on renal ischemia-reperfusion injury (IRI) were examined.Renal IRI in C57BL/6 mice was induced by clipping bilateral renal pedicles for 30 min, followed by reperfusion for 48 h. ERCs were isolated from healthy female menstrual blood, and were injected (1 million/mouse, i.v.) into mice 2 h prior to IRI induction. Renal function, pathological and immunohistological changes, cell populations and cytokine profiles were evaluated after 48 h of renal reperfusion.Here, we showed that as compared to untreated controls, administration of ERCs effectively prevented renal damage after IRI, indicated by better renal function and less pathological changes, which were associated with increased serum levels of IL-4, but decreased levels of TNF-, IFN- and IL-6. Also, ERC-treated mice displayed significantly less splenic and renal CD4(+) and CD8(+) T cell populations, while the percentage of splenic CD4(+)CD25(+) regulatory T cells and infiltrating M2 macrophages in the kidneys were significantly increased in ERC-treated mice.This study demonstrates that the novel anti-inflammatory and immunoregulatory effects of ERCs are associated with attenuation of renal IRI, suggesting that the unique features of ERCs may make them a promising candidate for cell therapies in the treatment of ischemic acute kidney injury in patients.


PubMed | Tianjin General Surgery Institute, Vancouver Coastal Health Research Institute and Tianjin Medical University
Type: Journal Article | Journal: Transplant immunology | Year: 2014

The potential of mesenchymal stem cells (MSCs) for immunosuppression has been tested in transplantation, but its mechanisms are not fully understood. This study investigated the role of MSC-expressing B7-H1 in the induction of immune tolerance to cardiac allografts by the combination therapy of MSCs and rapamycin (RAPA).The anti-alloimmunity of donor MSCs in the presence or absence of RAPA was examined in both mouse cardiac allograft model (C57BL/6 to BALB/c mice) and a variety of cultured immune cells. Immunohistochemical staining was used for the measurement of intragraft antibody deposition, and fluorescence-activated cell sorting (FACS) for the determination of serum alloantibodies and leukocyte phenotypes.B7-H1 expression in cultured MSCs was up-regulated following IFN- stimulation. In transplant recipients, combination therapy of MSCs and RAPA induced immune tolerance to allografts, but blockade of B7-H1 on MSCs with monoclonal antibody abrogated the combination therapy-induced immune tolerance as heart allografts were rejected. The negative effect of MSC-expressing B7-H1 neutralization on graft survival was correlated with a reduction of regulatory immune cells (CD4(+)CD25(+)Foxp3(+) T cells, tolerogenic dendritic cells and IL-4(high)IL-10(High)CD83(low) B cells), and also with an increase in alloantibody (IgG and IgM) levels both inside the grafts and in the circulation as compared with un-neutralized controls. In vitro MSC-mediated suppression of antibody production and B cell proliferation depended on B7-H1 function and cell contact between CD19(+) B cells and MSCs.These data suggest that MSC-expressing B7-H1 mediates the immune tolerance to cardiac allografts in recipients receiving MSC and RAPA combination therapy.

Loading Tianjin General Surgery Institute collaborators
Loading Tianjin General Surgery Institute collaborators