A novel xenograft model of human hepatocellular carcinoma in immunocompetent mice based on the microcarrier-6 |
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| Institution: | 1. Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao, Shandong, PR China;2. The Fourth Liver Disease Center, Beijing Youan Hospital, Capital Medical University, Beijing, PR China;3. Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, PR China;4. Department of Neurology, Qilu Hospital of Shandong University (Qingdao), Qingdao, Shandong, PR China;5. Institute of Liver Diseases, Affiliated Hospital of Jining Medical University, Shandong, PR China;6. Shanghai Meifeng Biotechnology Co., Ltd, Shanghai, PR China;1. Nephrology Department, Princess Alexandra Hospital, Brisbane, Queensland, Australia;2. Pathology Queensland, Brisbane, Queensland, Australia;1. Albany Medical Center, Albany, NY, United States of America;2. George Mason University, Fairfax, VA, United States of America;3. Division of Renal and Pancreatic Transplant Services, Albany Medical Center, Albany, NY, United States of America;1. Klinik am See, Rehabilitationszentrum, Rüdersdorf, Germany;2. Medical University Brandenburg \"Theodor Fontane\", Germany;3. Universität Potsdam, Professur für Rehabilitationswissenschaften, humanwissenschaftliche Fakultät, Germany;4. Clinic of Dermatology, Immunology and Allergology, Medical Center Dessau, Medical University Brandenburg \"Theodor Fontane\" Medical Center Dessau, Germany;1. Medical School of Ningbo University, Ningbo, Zhejiang, China;2. Department of Hepato-Pancreato-Biliary Surgery, Ningbo Medical Center Lihuili Hospital, The affiliated hospital of Ningbo University, Ningbo, Zhejiang, China;1. Department of Rheumatology, The Second Hospital of Shanxi Medical University, 030013 Taiyuan, Shanxi, China;2. Department of Pathology, Brigham and Women''s Hospital, Harvard Medical School, Boston, MA 02212, USA;1. School of Basic Medical Sciences, Ningxia Key Laboratory of Vascular Injury and Repair, Ningxia Medical University, Yinchuan 750004, Ningxia, China;2. Department of Pathology, Shanxi Province Cancer Hospital / Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences / Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan 030013, Shanxi, China;3. Department of Pathology, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China |
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| Abstract: | BackgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumors that threaten human health; thus, the establishment of an animal model with clinical features similar to human hepatocellular carcinoma is of important practical significance.MethodsTaking advantage of the novel microcarrier-6, human HCC cells were injected into immunocompetent mice to establish a novel human HCC patient-derived xenograft (PDX) model. Primary HCC cells were isolated from fresh hepatocellular carcinoma tissues, which were subsequently co-cultured with microcarrier-6 to construct a three-dimensional tumor cell culture model in vitro. The HCC-microcarrier complex was implanted into mice by subcutaneous inoculation, and the tumor formation time, tumor formation rate, and pathological manifestation were recorded. Changes of immune parameters in mice were detected by flow cytometry.ResultsThe success rate was 60% (6/10) in the establishment of hepatocellular carcinoma PDX mouse model, and the total tumor formation rate of the tumor-forming model is 90–100%. H&E staining and immunohistochemical experiments indicate that the model well retained the characteristics of the primary tumor. Interestingly, M2 macrophages in tumor-bearing mice increased significantly, and the levels of CD4+ T cells were significantly reduced.ConclusionsThrough the application of the microcarrier-6 in immunocompetent mice, we successfully established a novel human HCC PDX model, which can be used to better study and further elucidate the occurrence and pathogenic mechanism of HCC, improve the predictability of toxicity and drug sensitivity in HCC. |
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