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Hepatocyte and mesenchymal stem cell co-transplantation in rats with acute liver failure
Cheng-Maw Ho,Ya-Hui Chen,Chin-Sung Chien,Shu-Li Ho,Hui-Ling Chen,Rey-Heng Hu,Po-Huang Lee 대한이식학회 2020 Korean Journal of Transplantation Vol.34 No.2
Background: Cell therapy is considered a potential alternative to liver transplantation in acute liver failure (ALF). We aimed to evaluate the add-on therapeutic benefit of hepatocyte and mesenchymal stem cell (MSC) cotransplantation over hepatocyte-only transplantations in a rat model of ALF. Methods: ALF was induced by D-galactosamine in Sprague-Dawley rats. Freshly isolated donor hepatocytes were derived from Tg (UBC-emGFP) rats and MSCs were collected from the bone marrow cells of DsRed rats. Donor hepatocytes (1×107/mL) were intraportally transplanted 24 hours after treatment with D-galactosamine over a 70-second interval, and donor MSCs (0.5, 1, or 2×106/0.5 mL) were intraportally transplanted 1 hour after the hepatocyte transplantation was complete. Animals were sacrificed after 7 and 14 days and subjected to donor cell identification, liver histology, serologic testing, and immunohistopathological examination. Results: MSCs were observed in the periportal area, 1 and 2 weeks after transplantation. Transplanted hepatocytes did not actively proliferate when compared to hepatocyte-only transplantation. Morphologically, transplanted MSCs did not appear to differentiate into hepatocytes even 2 weeks after transplantation. Cotransplantation of MSCs was associated with lower macrophage infiltration, and reduced type I collagen, hepatocyte growth factor, tumor necrosis factor-α, and interleukin 10 expression, with similar gene expression profiles for epidermal growth factor and interleukin 6, when compared to hepatocyte-only transplantation. Conclusions: Hepatocyte and MSC cotransplantation is feasible and safe in rat models of ALF. MSCs were found to survive the process and could be located within the periportal niches 2 weeks after treatment, without enhancing transplanted hepatocyte proliferation or differentiating into hepatocytes, while ameliorating the inflammatory response.
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( Cheng-maw Ho ),( Shu-li Ho ),( Chia-tung Shun ),( Po-huang Lee ),( Ya-hui Chen ),( Chin-sung Chien ),( Hui-ling Chen ),( Rey-heng Hu ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: Primary liver progenitor cell cancer is a rare disease entity without definite evidence and characterization. Current nomenclature of primary liver cancer with prominent progenitor features is not comprehensive. This study was aimed to investigate the existence of this kind of primary liver cancer and characterize it immunohistopathologically based on the emerging understanding of cancer stem cell pathobiology. Methods: Surgical specimens from primary liver cancer which posed diagnostic difficulty fitting within current WHO classification of combined hepatocellular-cholangiocellular carcinoma with stem-cell features according to the growth morphology and its suggested immunohistochemical features, were stained with antibodies against well-defined markers of progenitor cells, stemness, and differentiation toward hepatocytes or cholangiocytes. Comparative interpretation of images was processed considering the histological morphology and characteristic markers. Results: The primary liver cancer consisted of CD24+ cancer progenitor cells and CD90+ mesenchymal stromal cells, which were intimately mixed. CD24+ cancer cells demonstrated bi-directional trends of differentiation: bile ductule transformation (cytokeratin 19+, epithelial cell adhesion molecule [EpCAM]+, neural cell adhesion molecule [NCAM]+, CD133+, and delta-like 1 homolog [DLK1]+); and trabecular or nested cell clusters toward hepatic lineage (hepatocyte nuclear factor-4 alpha [HNF-4α]+, Hep Par1+ and negative for CK19, EpCAM, CD133, and DLK1). Moderate lymphocyte (mostly CD4+ and CD8+ T cells) infiltrated in the CD90+ cancer- associated stroma. Conclusions: We provided the corroboration that liver progenitor cells can form primary liver cancer, not just presented as few side population of cancer stem cells. Its existence might pose significance for future stem cell therapeutic intervention targeting liver diseases, albeit the disease is rare.
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( Cheng-maw Ho ),( Go Wakabayashi ),( Chi-chuan Yeh ),( Rey- Heng Hu ),( Takanori Sakaguchi ),( Takeshi Takahara ),( Po- Huang Lee ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: Liver resection is a complex procedure for trainee sur geons. Cognitive task analysis facilitates understanding and decomposing tasks that require a great proportion of mental activity from experts. Methods: Using cognitive task analysis and video-based coaching to compare liver resection by open and laparoscopic approaches, we decomposed the task of liver resection into exposure (visual field building), adequate tension made at the working plane (which may change three-dimensionally during the resection process), and target processing (intervention strat egy) that can bridge the gap from the basic surgical principle. Results: The key steps of highly-specialized techniques, includ ing hanging maneuvers and looping of extra-hepatic hepatic veins, will be shown on video by open and laparoscopic ap proaches. Conclusions: Familiarization with laparoscopic anatomical orientation may help surgeons already skilled at open liver re section transit to perform laparoscopic liver resection smoothly. Facilities at hand (such as patient tolerability, advanced instru ments, and trained teams of personnel) can influence surgical decision making. Application of the rationale and realizing the interplay between the surgical principles and the other para medical factors may help surgeons in training to understand the mental abstractions of experienced surgeons, to choose the most appropriate surgical strategy effectively at will, and to minimize the gap.
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Kondo Interaction in FeTe and Its Potential Role in the Magnetic Order
Younsik Kim,Min-Seok Kim,Dongwook Kim,Minjae Kim,Minsoo Kim,Cheng-Maw Cheng,Joonyoung Choi,Saegyeol Jung,Donghui Lu,Jong Hyuk Kim,Soohyun Cho,Dongjoon Song,Dongjin Oh,Li Yu,Young Jai Choi,Hyeong-Do Ki 한국자기학회 2024 한국자기학회 학술연구발표회 논문개요집 Vol.34 No.1
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Nai-Yun Chang,Zeng-Weng Chen,Ter-Hsin Chen,Jiunn-Wang Liao,Cheng-Chung Lin,Maw-Sheng Chien,Wei-Cheng Lee,Jiunn-Horng Lin,Shih-Ling Hsuan 대한수의학회 2014 Journal of Veterinary Science Vol.15 No.1
Exotoxins produced by Actinobacillus (A.) pleuropneumoniae(Apx) play major roles in the pathogenesis of pleuropneumoniain swine. This study investigated the role of ApxI in hemolysisand cellular damage using a novel apxIA mutant, ApxIA336,which was developed from the parental strain A. pleuropneumoniae serotype 10 that produces only ApxI in vitro. The genotype of ApxIA336 was confirmed by PCR, Southernblotting, and gene sequencing. Exotoxin preparation derivedfrom ApxIA336 was analyzed for its bioactivity towardsporcine erythrocytes and alveolar macrophages. Analysisresults indicated that ApxIA336 contained a kanamycinresistantcassette inserted immediately after 1005 bp of theapxIA gene. Phenotype analysis of ApxIA336 revealed nodifference in the growth rate as compared to the parentalstrain. Meanwhile, ApxI production was abolished in thebacterial culture supernatant, i.e. exotoxin preparation. Theinability of ApxIA336 to produce ApxI corresponded to the lossof hemolytic and cytotoxic bioactivity in exotoxin preparation,as demonstrated by hemolysis, lactate dehydrogenase release,mitochondrial activity, and apoptosis assays. Additionally, thevirulence of ApxIA336 appeared to be attenuated by 15-fold inBALB/c mice. Collectively, ApxI, but not other components inthe exotoxin preparation of A. pleuropneumoniae serotype 10,was responsible for the hemolytic and cytotoxic effects onporcine erythrocytes and alveolar macrophages.
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Tung-Hung Su,Chih-Horng Wu,Tsung-Hao Liu,Cheng-Maw Ho,Chun-Jen Liu 대한간학회 2023 Clinical and Molecular Hepatology(대한간학회지) Vol.29 No.2
Hepatocellular carcinoma (HCC) is the fourth most common cancer and the second leading cause of cancer-related death in Taiwan. The Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan developed and updated the guidelines for HCC management in 2020. In clinical practice, we follow these guidelines and the reimbursement policy of the government. In Taiwan, abdominal ultrasonography, alpha-fetoprotein, and protein induced by vitamin K absence or antagonist-II (PIVKA-II) tests are performed for HCC surveillance every 6 months or every 3 months for high-risk patients. Dynamic computed tomography, magnetic resonance imaging, and contrast-enhanced ultrasound have been recommended for HCC surveillance in extremely high-risk patients or those with poor ultrasonographic visualization results. HCC is usually diagnosed through dynamic imaging, and pathological diagnosis is recommended. Staging of HCC is based on a modified version of the Barcelona Clinic Liver Cancer (BCLC) system, and the HCC management guidelines in Taiwan actively promote curative treatments including surgery and locoregional therapy for BCLC stage B or C patients. Transarterial chemoembolization (TACE), drug-eluting bead TACE, transarterial radioembolization, and hepatic artery infusion chemotherapy may be administered for patients with BCLC stage B or C HCC. Sorafenib and lenvatinib are reimbursed as systemic therapies, and regorafenib and ramucirumab may be reimbursed in cases of sorafenib failure. First-line atezolizumab with bevacizumab is not yet reimbursed but may be administered in clinical practice. Systemic therapy and external beam radiation therapy may be used in specific patients. Early switching to systemic therapy in TACE-refractory patients is a recent paradigm shift in HCC management.
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