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Tang X.-J.,Hubei University of Medicine | Sun X.-Y.,Institute of Transplant Medicine | Huang K.-M.,Hubei University of Medicine | Zhang L.,Hubei University of Medicine | And 8 more authors.
Oncotarget | Year: 2015

Chimeric antigen receptor (CAR)-based T-cell adoptive immunotherapy is a distinctively promising therapy for cancer. The engineering of CARs into T cells provides T cells with tumor-targeting capabilities and intensifies their cytotoxic activity through stimulated cell expansion and enhanced cytokine production. As a novel and potent therapeutic modality, there exists some uncontrollable processes which are the potential sources of adverse events. As an extension of this impactful modality, CAR-T cell-derived exosomes may substitute CAR-T cells to act as ultimate attackers, thereby overcoming some limitations. Exosomes retain most characteristics of parent cells and play an essential role in intercellular communications via transmitting their cargo to recipient cells. The application of CAR-T cell-derived exosomes will make this cell-based therapy more clinically controllable as it also provides a cell-free platform to diversify anticancer mediators, which responds effectively to the complexity and volatility of cancer. It is believed that the appropriate application of both cellular and exosomal platforms will make this effective treatment more practicable. Source

Moniri M.R.,University of British Columbia | Sun X.-Y.,Institute of Transplant Medicine | Rayat J.,University of British Columbia | Dai D.,University of British Columbia | And 5 more authors.
Cancer Gene Therapy | Year: 2012

Mesenchymal stem cells (MSCs) have attracted great interest in cancer therapy owing to their tumor-oriented homing capacity and the feasibility of autologous transplantation. Currently, pancreatic cancer patients face a very poor prognosis, primarily due to the lack of therapeutic strategies with an effective degree of specificity. Anticancer gene-engineered MSCs specifically target tumor sites and can produce anticancer agents locally and constantly. This study was performed to characterize pancreas-derived MSCs and investigate the effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-engineered MSCs on pancreatic cancer cells under different culture conditions. Pancreas-derived MSCs exhibited positive expression on CD44, CD73, CD95, CD105, negative on CD34 and differentiated into adipogenic and osteogenic cells. TRAIL expression was assessed by both enzyme-linked immunosorbent assay and western blot analysis. Different patterns of TRAIL receptor expression were observed on the pancreatic cancer cell lines, including PANC1, HP62, ASPC1, TRM6 and BXPC3. Cell viability was assessed using a real-time monitoring system. Pancreatic cancer cell death was proportionally related to conditioned media from MSC nsTRAIL and MSC stTRAIL. The results suggest that MSCs exhibit intrinsic inhibition of pancreatic cancer cells and that this effect can be potentiated by TRAIL-transfection on death receptor-bearing cell types. © 2012 Nature America, Inc. All rights reserved. Source

Li M.,Guangxi Medical University | Li M.,Guangxi University | Sun X.,Institute of Transplant Medicine | Sun X.,Guangxi Key Laboratory for Transplantation Medicine | And 5 more authors.
Clinical and Experimental Immunology | Year: 2014

Bone marrow mesenchymal stem cells (BMSCs) inhibit immune cell responsiveness, and especially of T lymphocytes. We showed that BMSCs markedly inhibited the proliferation and cytokine production by CD8+ T cells by a cell-to-cell contact phenomenon and secretion of soluble factors. BMSCs down-regulate the expression of natural killer group 2, member D protein (NKG2D) receptors on CD8+ T cells when co-cultured with them. Moreover, CD8+ T cells that express low levels of NKG2D had impaired proliferation after triggering by a mitogen. The major histocompatibility complex (MHC) class I chain-related (MIC) A/B molecule, which is a typical ligand for NKG2D, was expressed on BMSCs, and caused dampening of cell proliferation. Monoclonal antibody blocking experiments targeted to MIC A/B impaired CD8+ T cell function, as evaluated by proliferation and cytokine production. In addition, the production of prostaglandin E2 (PGE2), indoleamine 2, 3-dioxygenase (IDO) and transforming growth factor (TGF)-β1 were increased when BMSCs were co-cultured with CD8+ T cells. The addition of specific inhibitors against PGE2, IDO and TGF-β partially restored the proliferation of CD8+ T cells. Our results suggest that BMSCs suppress CD8+ T cell-mediated activation by suppressing NKG2D expression and secretion of PGE2, IDO and TGF-β. Our observations further confirm the feasibility of BMSCs as a potential adoptive cellular therapy in immune-mediated diseases such as graft-versus-host disease (GVHD). © 2014 British Society for Immunology. Source

Sun X.Y.,Institute of Transplant Medicine | Dong J.H.,Institute of Transplant Medicine | Qin K.,Institute of Transplant Medicine | Lan L.G.,Institute of Transplant Medicine | And 6 more authors.
Experimental and Therapeutic Medicine | Year: 2016

Effective use of all available donated organs is critical, in order to meet the increasing demand for transplants. The present study explored liver transplantation with livers that were donated following cardiac death (DCD). According to the guidelines established by The Red Cross Society of China, 42 DCD organs were procured. Selected donors were treated with extracorporeal membrane oxygenation (ECMO) prior to the organ retrieval. The present single center study included 6 liver transplantations of DCD organs (5 liver transplants and 1 liver kidney combined transplant). All 6 recipients had a successful recovery without significant complications. The serum alanine transaminase, total bilirubin and international normalized ratio returned to the normal levels within a short period of time following transplantation, and the liver function remained normal during the follow up period, which lasted up to 24 months. The present report demonstrated the feasibility of orthotopic liver transplantation using DCD livers. The pre conditioning DCD donors and optimization of the recipi­ent's condition using ECMO, played a crucial role in ensuring the success of transplantation. © 2016, Spandidos Publications. All Rights reserved. Source

Sun X.-Y.,Institute of Transplant Medicine | Nong J.,Institute of Transplant Medicine | Ke Q.,Institute of Transplant Medicine | Lu H.,University of British Columbia | And 3 more authors.
Anticancer Research | Year: 2011

Background: Mesenchymal stem cells (MSCs) have attracted great interest in cancer therapy since the discovery of their tumor tropism. This study was performed to investigate the effects of TNF-related apoptosis-inducing ligand (TRAIL)-engineered MSCs on hepatocellular carcinoma (HCC) cells (HepG2) under different culture conditions. Materials and Methods: MSCs engineered with non-secreting TRAIL (MSC TRAIL-GFP) (GFP, green fluorescence protein) and secreting TRAIL (MSC stTRAIL) were used for the direct co-cultures, and conditioned media (CM) from corresponding cultures were applied to HepG2 as indirect co-cultures. Immunoblotting, ELISA and FACS analysis were used to detect the expression of TRAIL and TRAIL receptors. Cell death was assessed using live/dead assay. Results: Death receptor (DR) 5 was identified on the HepG2 cells. The expression of TRAIL was confirmed in the cell lysates (MSC TRAIL-GFP >MSC stTRAIL) and the conditioned media (MSC stTRAIL >MSC TRAIL-GFP). Higher cell death was observed in high MSCIHepG2 ratio cocultures. HepG2 cell death was proportionally related to CM from MSC TRAIL-GFP and MSC stTRAIL. Conclusion: MSCs exhibit intrinsic inhibition of HepG2 which is potentiated by TRAIL-transfection. Source

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