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Gasparini P, Casanova M, Centonze G, Borzi C, Bergamaschi L, Collini P, Testi A, Chiaravalli S, Massimino M, Sozzi G, Ferrari A, Moro M. Establishment of 6 pediatric rhabdomyosarcoma patient’s derived xenograft models closely recapitulating patients’ tumor characteristics. TUMORI JOURNAL 2022:3008916221110266. [PMID: 36114629 DOI: 10.1177/03008916221110266] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Introduction: The prognosis for patients with metastatic and recurrent pediatric rhabdomyosarcoma (RMS) remains poor. The availability of preclinical models is essential to identify promising treatments We established a series of pediatric RMS patient derived xenografts (PDXs), all faithfully mirroring primary tumor characteristics and representing a unique tool for clarifying the biological processes underlying RMS progression and relapse. Methods: Fresh tumor samples from 12 RMS patients were implanted subcutaneously in both flanks of immunocompromised mice. PDXs were considered as grafted after accomplishing three passages in mice. Characterization of tumor tissues and models was performed by comparing both morphology and immunoistochemical and fluorescence in situ hybridization (FISH) characteristics. Results: Six PDXs were established, with a successful take rate of 50%. All models closely mirrored parental tumor characteristics. An increased grafting rate for tumors derived from patients with worse outcome (p = 0.006) was detected. For 50% PDXs grafting occurred when the corresponding patient was still alive. Conclusion: Our findings increase the number of available RMS PDX models and strengthen the role of PDXs as useful preclinical tools for patients with unmet medical needs and to develop personalized therapies.
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Affiliation(s)
- Patrizia Gasparini
- Tumor Genomics Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Michela Casanova
- Paediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Giovanni Centonze
- First Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
| | - Cristina Borzi
- Tumor Genomics Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Luca Bergamaschi
- Paediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Paola Collini
- Soft Tissue and Bone Pathology, Histopathology and Pediatric Pathology Unit, Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Adele Testi
- Laboratory of Molecular Pathology, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Stefano Chiaravalli
- Paediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Maura Massimino
- Paediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Gabriella Sozzi
- Tumor Genomics Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Andrea Ferrari
- Paediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Massimo Moro
- Tumor Genomics Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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Pan Y, Liao X, Yang L, Zhang C, Wang J, Zheng P, Yu G, Song H. Extract of Marsdenia tenacissima (Roxb.) Moon [Apocynaceae] Suppresses Hepatocellular Carcinoma by Inhibiting Angiogenesis. Front Pharmacol 2022; 13:900128. [PMID: 35847002 PMCID: PMC9279733 DOI: 10.3389/fphar.2022.900128] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Accepted: 05/19/2022] [Indexed: 12/01/2022] Open
Abstract
The extract of Marsdeniatenacissima (Roxb.) Moon [Apocynaceae] (MTE) has shown a significant anti-cancer effect on hepatocellular carcinoma (HCC), but its mechanism remains unclear. In this study, we used transcriptomics methods to investigate the underlying mechanism of MTE against HCC. Both MHCC97H and HepG2 cell lines were treated with MTE. The cell viability and migration were measured using the cell counting kit-8 assay and transwell assay. RNA-sequencing was used to identify differentially expressed genes (DEGs) between HepG2 cells treated with and without MTE. The expression levels of selected DEGs—vascular endothelial growth factor-A (VEGFA), platelet-derived growth factor receptor-β (PDGFRB), and von Willebrand factor (VWF)—were verified by RT-PCR and Western blot. The effect of conditioned medium from HCC cells with MTE treatment (CM-MTE) on blood vessels was observed by tube formation assay of HUVECs and chick chorioallantoic membrane (CAM) assay. A mouse model of HCC patient-derived tumor xenograft (PDX) was established and treated with MTE. The effect of MTE on the growth and angiogenesis of HCC-PDX was analyzed. The results demonstrated that MTE inhibited the viability and migration of HCC cells. RNA-seq showed that MTE treatment downregulated multiple genes associated with metabolism and angiogenesis. The expression levels of VEGFA, VWF, PDGFB, and PDGFRB in HCC cells were significantly suppressed by MTE. Meanwhile, MTE effectively inhibited the tube-forming capability of HUVECs and the angiogenesis of chick CAM. In vivo experiments revealed that the extract reduced tumor volume, inhibited the proliferation of HCC cells, and expanded the necrotic area of the tumor. Immunohistochemical results showed that the expression levels of CD31, PDGFB, VEGF, VWF, and PDGFRB in the HCC-PDX tumor tissues were all downregulated by MTE in a dose-dependent manner. Taken together, MTE could inhibit angiogenesis by repressing the expression of VEGF, VWF, PDGF, and PDGFRB in HCC cells, a mechanism that may enable MTE to counter HCC development.
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Affiliation(s)
- Yating Pan
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xinyi Liao
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lili Yang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Chunlei Zhang
- Department of Emergency, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jue Wang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Peiyong Zheng
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- *Correspondence: Guanzhen Yu, ; Haiyan Song, ; Peiyong Zheng,
| | - Guanzhen Yu
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- *Correspondence: Guanzhen Yu, ; Haiyan Song, ; Peiyong Zheng,
| | - Haiyan Song
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- *Correspondence: Guanzhen Yu, ; Haiyan Song, ; Peiyong Zheng,
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Gu CY, Lee TKW. Preclinical mouse models of hepatocellular carcinoma: An overview and update. Exp Cell Res 2022; 412:113042. [PMID: 35101391 DOI: 10.1016/j.yexcr.2022.113042] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 01/15/2022] [Accepted: 01/19/2022] [Indexed: 11/29/2022]
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Role of Biobanks for Cancer Research and Precision Medicine in Hepatocellular Carcinoma. J Gastrointest Cancer 2021; 52:1232-1247. [PMID: 34807351 DOI: 10.1007/s12029-021-00759-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/05/2021] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is a highly complex and deadly cancer. There is an urgent need for new and effective treatment modalities. Since the primary goal in the management of cancer is to cure and improve survival, personalized therapy can increase survival, reduce mortality rates, and improve quality of life. Biobanks hold potential in leading to breakthroughs in biomedical research and precision medicine (PM). They serve as a biorepository, collecting, processing, storing, and supplying specimens and relevant data for basic, translational, and clinical research. OBJECTIVE We aimed to highlight the fundamental role of biobanks, harboring high quality, sustainable collections of patient samples in adequate size and variability, for developing diagnostic, prognostic, and predictive biomarkers to develop and PM approaches in the management of HCC. METHOD We obtained information from previously published articles and BBMRI directory. RESULTS AND CONCLUSION Biobanking of high-quality biospecimens along with patient clinical information provides a fundamental scientific infrastructure for basic, translational, and clinical research. Biobanks that control and eliminate pre-analytical variability of biospecimens, provide a platform to identify reliable biomarkers for the application of PM. We believe, establishing HCC biobanks will empower to underpin molecular mechanisms of HCC and generate strategies for PM. Thus, first, we will review current therapy approaches in HCC care. Then, we will summarize challenges in HCC management. Lastly, we will focus on the best practices for establishing HCC biobanking to support research, translational medicine in the light of new experimental research conducted with the aim of delivering PM for HCC patients.
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DNMT1-mediated methylation of BEX1 regulates stemness and tumorigenicity in liver cancer. J Hepatol 2021; 75:1142-1153. [PMID: 34217777 DOI: 10.1016/j.jhep.2021.06.025] [Citation(s) in RCA: 88] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 05/04/2021] [Accepted: 06/14/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) both exhibit notable cancer stem cell (CSC) features. Moreover, the development of both diseases is closely associated with the presence of CSCs. We investigated the role of brain-expressed X-linked protein 1 (BEX1) in regulating the CSC properties of HB and a subtype of HCC with high CSC features (CSC-HCC). METHODS Stemness scores were analyzed in 5 murine HCC models. A subpopulation of BEX1-positive cells and BEX1-negative cells were sorted from HCC cell lines, and subjected to transcriptome analysis. The expression and function of BEX1 was examined via western blotting, sphere formation assays, and xenograft tumor models. RESULTS We identified BEX1 as a novel CSC marker that was required for the self-renewal of liver CSCs. Furthermore, zebularine, a potent DNMT1 inhibitor, can induce the reactivation of BEX1 by removing epigenetic inhibition. Notably, BEX1 was highly expressed in patients with HB and CSC-HCC, but not in patients with non-CSC HCC. Moreover, DNMT1-mediated methylation of the BEX1 promoter resulted in differential BEX1 expression patterns in patients with HB, CSC-HCC, and non-CSC-HCC. Mechanistically, BEX1 interacted with RUNX3 to block its inhibition of β-catenin transcription, which led to the activation of Wnt/β-catenin signaling, and stemness maintenance in both HB and CSC-HCC. In contrast, downregulated BEX1 expression released RUNX3 and inhibited the activation of Wnt/β-catenin signaling in non-CSC-HCC. CONCLUSION BEX1, under the regulation of DNMT1, is necessary for the self-renewal and maintenance of liver CSCs through activation of Wnt/β-catenin signaling, rendering BEX1 a potentially valuable therapeutic target in both HB and CSC-HCC. LAY SUMMARY Cancer stem cells (CSCs) contribute to a high rate of cancer recurrence, as well as resistance to conventional therapies. However, the regulatory mechanisms underlying their self-renewal remains elusive. Herein, we have reported that BEX1 plays a key role in regulating CSC properties in different types of liver cancer. Targeting BEX1-mediated Wnt/β-catenin signaling may help to address the high rate of recurrence, and heterogeneity of liver cancer.
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Xing JL, Wang YX, Du SD. Application and research progress of in vitro liver cancer cell culture models. Shijie Huaren Xiaohua Zazhi 2021; 29:563-570. [DOI: 10.11569/wcjd.v29.i11.563] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Liver cancer is gradually becoming an important burden on public health around the world, and many drugs are currently available for the treatment of liver cancer, so the correct choice of drugs will significantly improve the prognosis of patients. In vitro liver cancer cell culture model is an important way to study the pathogenesis of liver cancer and drug screening. Long-term practice has proved that the traditional two-dimensional (2D) drug screening method cannot truly reproduce the complex drug resistance mechanism of tumor. The emergence of in vitro three-dimensional (3D) hepatocellular carcinoma cell model enriches the selection of methods for hepatoma experiments in vitro. The experimental sensitivity of hepatoma drugs in vitro and the study of pathology and physiology of hepatoma cells in vitro have also been greatly improved. In this paper, we review the main types of liver cancer cells cultured in vitro and discuss their advantages and disadvantages, in order to clarify the development and research direction of in vitro liver cancer culture models.
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Affiliation(s)
- Jia-Li Xing
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Yu-Xin Wang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Shun-Da Du
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
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Huang DQ, Muthiah MD, Zhou L, Jumat H, Tan WX, Lee GH, Lim SG, Kow A, Bonney G, Shridhar I, Lim YT, Wee A, Pang YH, Soon G, Chow P, Dan YY. Predicting HCC Response to Multikinase Inhibitors With In Vivo Cirrhotic Mouse Model for Personalized Therapy. Cell Mol Gastroenterol Hepatol 2020; 11:1313-1325. [PMID: 33340714 PMCID: PMC8020437 DOI: 10.1016/j.jcmgh.2020.12.009] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 12/11/2020] [Accepted: 12/14/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Hepatocellular carcinoma (HCC) arises in a cirrhotic, pro-angiogenic microenvironment. Inhibiting angiogenesis is a key mode of action of multikinase inhibitors and current non-cirrhotic models are unable to predict treatment response. We present a novel mouse cirrhotic model of xenotransplant that predicts the natural biology of HCC and allows personalized therapy. METHODS Cirrhosis was induced in NOD Scid gamma mice with 4 months of thioacetamide administration. Patient derived xenografts (PDXs) were created by transplant of human HCC subcutaneously into non-cirrhotic mice and intra-hepatically into both cirrhotic and non-cirrhotic mice. The applicability of cirrhotic PDXs for drug testing was tested with 16 days of either sorafenib or lenvatinib. Treatment response was evaluated by MRI. RESULTS 8 out of 19 (42%) human HCC engrafted in the cirrhotic model compared with only 3 out of 19 (16%) that engrafted in the subcutaneous non-cirrhotic model. Tumor vasculature was preserved in the cirrhotic model but was diminished in the non-cirrhotic models. Metastasis developed in 3 cirrhotic PDX lines and was associated with early HCC recurrence in all 3 corresponding patients (100%), compared with only 5 out of 16 (31%) of the other PDX lines, P = .027. The cirrhotic model was able to predict response and non-response to lenvatinib and sorafenib respectively in the corresponding patients. Response to lenvatinib in the cirrhotic PDX was associated with reduction in CD34, VEGFR2 and CLEC4G immunofluorescence area and intensity (all P ≤ .03). CONCLUSIONS A clinically relevant cirrhotic PDX model preserves tumor angiogenesis and allows prediction of response to multikinase inhibitors for personalized therapy.
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Affiliation(s)
- Daniel Q Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Mark D Muthiah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Lei Zhou
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Halisah Jumat
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wan Xin Tan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Guan Huei Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Seng Gee Lim
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Alfred Kow
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, National University Health System, Singapore
| | - Glenn Bonney
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, National University Health System, Singapore
| | - Iyer Shridhar
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, National University Health System, Singapore
| | - Yi Ting Lim
- Department of Diagnostic Imaging, National University Health System, Singapore
| | - Aileen Wee
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, National University Hospital, National University Health System, Singapore
| | - Yin Huei Pang
- Department of Pathology, National University Hospital, National University Health System, Singapore
| | - Gwyneth Soon
- Department of Pathology, National University Hospital, National University Health System, Singapore
| | - Pierce Chow
- Division of Surgical Oncology, National Cancer Center Singapore, Singapore; Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-NUS Medical School Singapore, Singapore
| | - Yock Young Dan
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
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Xie F, Sun L, Pang Y, Xu G, Jin B, Xu H, Lu X, Xu Y, Du S, Wang Y, Feng S, Sang X, Zhong S, Wang X, Sun W, Zhao H, Zhang H, Yang H, Huang P, Mao Y. Three-dimensional bio-printing of primary human hepatocellular carcinoma for personalized medicine. Biomaterials 2020; 265:120416. [PMID: 33007612 DOI: 10.1016/j.biomaterials.2020.120416] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 08/30/2020] [Accepted: 09/19/2020] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most lethal tumors worldwide. This study aims to address the lack of faithful and available in vitro models for patient-specific drug screening for HCC. We recently established a novel modeling system using three-dimensional (3D) bioprinting technology and constructed hepatorganoids with HepaRG cells, which retain the liver function and prolong the survival of mice with liver failure after abdominal transplantation. Here we extend this modeling system to establish individualized model for hepatocellular carcinoma. HCC specimens were obtained from six patients after surgery. Primary HCC cells were isolated and mixed with gelatin and sodium alginate to form the bioink for printing. Patient-derived three-dimensional bio-printed HCC (3DP-HCC) models were successfully established afterward and grew well during long-term culture. These models retained the features of parental HCCs, including stable expression of the biomarker, stable maintenances of the genetic alterations and expression profiles. 3DP-HCC models are capable of displaying the results of drug screening intuitively and quantitatively. In conclusion, 3DP-HCC models are faithful in vitro models that are reliable in long-term culture and able to predict patient-specific drugs for personalized treatment.
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Affiliation(s)
- Feihu Xie
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, China
| | - Lejia Sun
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, China
| | - Yuan Pang
- Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China; Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing, 100084, China; Overseas Expertise Introduction Center for Discipline Innovation, Tsinghua University, Beijing, 100084, China
| | - Gang Xu
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, China
| | - Bao Jin
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, China
| | - Haifeng Xu
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, China
| | - Xin Lu
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, China
| | - Yiyao Xu
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, China
| | - Shunda Du
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, China
| | - Yanan Wang
- State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, PUMC & CAMS, Beijing, 100005, China
| | - Shi Feng
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, China
| | - Xinting Sang
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, China
| | - Shouxian Zhong
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, China
| | - Xin Wang
- Research Center for Laboratory Animal Science, Inner Mongolia University, Huhhot, 010021, China; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, 55455, USA; Hepatoscience Section, Cell Lab Tech Inc., Sunnyvale, CA, 94085, USA
| | - Wei Sun
- Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China; Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing, 100084, China; Overseas Expertise Introduction Center for Discipline Innovation, Tsinghua University, Beijing, 100084, China; Department of Mechanical Engineering, Drexel University, Philadelphia, PA, 19104, USA
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, China
| | - Hongbing Zhang
- State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, PUMC & CAMS, Beijing, 100005, China
| | - Huayu Yang
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, China.
| | - Pengyu Huang
- School of Life Science and Technology, Shanghai Tech University, Shanghai, 201210, China; CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, 200031, China.
| | - Yilei Mao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, China.
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