14 results on '"Yoshio, Marumoto"'
Search Results
2. Hepatic crown-like structure: a unique histological feature in non-alcoholic steatohepatitis in mice and humans.
- Author
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Michiko Itoh, Hideaki Kato, Takayoshi Suganami, Kuniha Konuma, Yoshio Marumoto, Shuji Terai, Hiroshi Sakugawa, Sayaka Kanai, Miho Hamaguchi, Takahiro Fukaishi, Seiichiro Aoe, Kazunari Akiyoshi, Yoshihiro Komohara, Motohiro Takeya, Isao Sakaida, and Yoshihiro Ogawa
- Subjects
Medicine ,Science - Abstract
Although macrophages are thought to be crucial for the pathogenesis of chronic inflammatory diseases, how they are involved in disease progression from simple steatosis to non-alcoholic steatohepatitis (NASH) is poorly understood. Here we report the unique histological structure termed "hepatic crown-like structures (hCLS)" in the mouse model of human NASH; melanocortin-4 receptor deficient mice fed a Western diet. In hCLS, CD11c-positive macrophages aggregate to surround hepatocytes with large lipid droplets, which is similar to those described in obese adipose tissue. Histological analysis revealed that hCLS is closely associated with activated fibroblasts and collagen deposition. When treatment with clodronate liposomes effectively depletes macrophages scattered in the liver, with those in hCLS intact, hepatic expression of inflammatory and fibrogenic genes is unaffected, suggesting that hCLS is an important source of inflammation and fibrosis during the progression of NASH. Notably, the number of hCLS is positively correlated with the extent of liver fibrosis. We also observed increased number of hCLS in the liver of non-alcoholic fatty liver disease/NASH patients. Collectively, our data provide evidence that hCLS is involved in the development of hepatic inflammation and fibrosis, thereby suggesting its pathophysiologic role in disease progression from simple steatosis to NASH.
- Published
- 2013
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3. Treatment strategies for advanced hepatocellular carcinoma: Sorafenib vs hepatic arterial infusion chemotherapy
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Toshihiko Matsumoto, Takuro Hisanaga, Taro Takami, Issei Saeki, Takahiro Yamasaki, Yoshio Marumoto, Yutaka Suehiro, Isao Hidaka, Tsuyoshi Ishikawa, Isao Sakaida, Naoki Yamamoto, Takuya Iwamoto, Masaki Maeda, and Koichi Fujisawa
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Oncology ,Sorafenib ,medicine.medical_specialty ,Hepatology ,business.industry ,medicine.disease ,digestive system diseases ,Additional research ,law.invention ,Clinical trial ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Internal medicine ,Hepatic arterial infusion chemotherapy ,medicine ,Treatment strategy ,030211 gastroenterology & hepatology ,Transcatheter arterial chemoembolization ,business ,neoplasms ,medicine.drug - Abstract
Sorafenib is used worldwide as a first-line standard systemic agent for advanced hepatocellular carcinoma (HCC) on the basis of the results of two large-scale Phase III trials. Conversely, hepatic arterial infusion chemotherapy (HAIC) is one of the most recommended treatments in Japan. Although there have been no randomized controlled trials comparing sorafenib with HAIC, several retrospective analyses have shown no significant differences in survival between the two therapies. Outcomes are favorable for HCC patients exhibiting macroscopic vascular invasion when treated with HAIC rather than sorafenib, whereas in HCC patients exhibiting extrahepatic spread or resistance to transcatheter arterial chemoembolization, good outcomes are achieved by treatment with sorafenib rather than HAIC. Additionally, sorafenib is generally used to treat patients with Child-Pugh A, while HAIC is indicated for those with either Child-Pugh A or B. Based on these findings, we reviewed treatment strategies for advanced HCC. We propose that sorafenib might be used as a first-line treatment for advanced HCC patients without macroscopic vascular invasion or Child-Pugh A, while HAIC is recommended for those with macroscopic vascular invasion or Child-Pugh A or B. Additional research is required to determine the best second-line treatment for HAIC non-responders with Child-Pugh B through future clinical trials.
- Published
- 2018
4. Effectiveness of Early Intervention by Specialized Institutions for Liver Cirrhosis Patients
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Toshihiko Matsumoto, Yoshio Marumoto, Takuro Hisanaga, Isao Sakaida, Taro Takami, Takuya Iwamoto, Isao Hidaka, Issei Saeki, Tsuyoshi Ishikawa, Masaki Maeda, and Takahiro Yamasaki
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medicine.medical_specialty ,Cirrhosis ,business.industry ,Intervention (counseling) ,Medicine ,General Medicine ,business ,Intensive care medicine ,medicine.disease - Published
- 2017
5. Association of tyrosine with insulin resistance in hepatitis C virus-related chronic liver disease
- Author
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Issei Saeki, Takuya Iwamoto, Ichiro Kunitugu, Tsuyoshi Tanabe, Takahiro Yamasaki, Junichi Zaitsu, Isao Sakaida, Koichi Uchida, Makoto Segawa, Isao Hidaka, Yumiko Harima, Takashi Oono, Yoshio Marumoto, Taro Takami, Yohei Urata, Shuji Terai, and Tsuyoshi Ishikawa
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Prothrombin time ,medicine.medical_specialty ,Hepatology ,medicine.diagnostic_test ,Bilirubin ,business.industry ,Hepatitis C virus ,Albumin ,medicine.disease_cause ,Chronic liver disease ,medicine.disease ,chemistry.chemical_compound ,Infectious Diseases ,Endocrinology ,Insulin resistance ,chemistry ,Internal medicine ,Hepatocellular carcinoma ,medicine ,Tyrosine ,business - Abstract
Aim Insulin resistance (IR) increases during the early stages of hepatitis C virus (HCV)-related chronic liver disease and is a sign of poor prognosis as well as a risk factor for hepatic fibrosis and hepatocellular carcinoma. We aimed to determine the factors affecting IR in HCV-related chronic liver disease. Methods We retrospectively examined 71 patients with HCV-related chronic liver disease and analyzed various parameters, including amino acids, as possible predictors of IR. IR was assessed using the Homeostasis Model of Assessment – Insulin Resistance (HOMA-IR). Amino acids were assayed by examining branched-chain amino acids (BCAA), tyrosine level, and the ratio of BCAA to tyrosine level (BTR). Results HOMA-IR was significantly correlated with body mass index, platelet count, prothrombin time, hemoglobin, total bilirubin, total protein, albumin, total cholesterol, fasting glucose, BTR (r = −0.46, P = 0.0001) and tyrosine (r = 0.55, P
- Published
- 2013
6. Serum transferrin as a predictor of prognosis for hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma
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Seiji Kaino, Shuji Terai, Tsuyoshi Ishikawa, Naoki Yamamoto, Isao Sakaida, Yoshio Marumoto, Toshihiko Matsumoto, Takuya Iwamoto, Yohei Urata, Taro Takami, Yohei Harima, Isao Hidaka, Issei Saeki, Koichi Uchida, Takahiro Yamasaki, Yumiko Harima, and Junichi Zaitsu
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chemistry.chemical_classification ,medicine.medical_specialty ,Hepatology ,business.industry ,Therapeutic effect ,Hazard ratio ,Cumulative survival ,medicine.disease ,Gastroenterology ,Confidence interval ,Surgery ,Deferoxamine ,Infectious Diseases ,chemistry ,Transferrin ,Hepatocellular carcinoma ,Internal medicine ,Hepatic arterial infusion chemotherapy ,medicine ,business ,medicine.drug - Abstract
Aim We recently reported that the iron chelator deferoxamine (DFO) is efficacious in advanced hepatocellular carcinoma (HCC) patients. Iron regulation may thus have an important impact in HCC therapy. Because transferrin is a native chelator that regulates iron homeostasis, it may act as an anticancer agent in a similar manner as DFO. The objective of this study was to evaluate serum transferrin as a prognostic predictor in advanced HCC patients undergoing hepatic arterial infusion chemotherapy (HAIC). Methods We retrospectively studied 44 patients receiving HAIC and analyzed various parameters for their possible use as prognostic predictors. Results The 1-, 2- and 3-year cumulative survival rates were 36.4%, 18.2% and 8.5%, respectively, and the median survival time (MST) was 7.0 months. The survival rates of patients who had serum transferrin of 190 mg/dL or more (MST, 12.0 months) were significantly better than those of patients who had serum transferrin of less than 190 mg/dL (MST, 4.9 months). Multivariate analysis identified serum transferrin of 190 mg/dL or more (hazard ratio [HR], 0.282; 95% confidence interval [CI], 0.132–0.603; P = 0.001) and Child–Pugh score B (HR, 1.956; 95% CI, 1.034–3.700; P = 0.039) as independent prognostic predictors. There was a significant correlation between serum transferrin level and therapeutic effect (P
- Published
- 2013
7. Administration of fibroblast growth factor 2 in combination with bone marrow transplantation synergistically improves carbon-tetrachloride-induced liver fibrosis in mice
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Yuko Mizunaga, Koh Shinoda, Naoki Yamamoto, Tomoaki Murata, Yoshio Marumoto, Koji Aoyama, Yohei Urata, Isao Sakaida, Shuji Terai, Tsuyoshi Ishikawa, and Hiroshi Nishina
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medicine.medical_specialty ,Histology ,Cirrhosis ,Apoptosis ,Liver Cirrhosis, Experimental ,Fibroblast growth factor ,Pathology and Forensic Medicine ,Extracellular matrix ,Cell therapy ,Mice ,Internal medicine ,In Situ Nick-End Labeling ,medicine ,Animals ,Fluorescent Antibody Technique, Indirect ,Bone Marrow Transplantation ,Cell Proliferation ,integumentary system ,business.industry ,Cell Biology ,medicine.disease ,Combined Modality Therapy ,Mice, Inbred C57BL ,Transplantation ,Ki-67 Antigen ,surgical procedures, operative ,Endocrinology ,Liver ,Matrix Metalloproteinase 9 ,embryonic structures ,Cancer research ,Female ,Fibroblast Growth Factor 2 ,Tumor necrosis factor alpha ,Liver function ,business - Abstract
We previously reported that fibroblast growth factor 2 (FGF2) facilitated the differentiation of transplanted bone marrow cells (BMCs) into hepatocytes. Our earlier study also demonstrated that administration of FGF2 in combination with bone marrow transplantation (BMT) synergistically activated tumor necrosis factor-alpha signaling and significantly improved liver function and prognosis more than BMT alone. However, the way that it affected the extracellular matrix remained unclear. Here, we investigated the effect of FGF2 treatment together with BMT on liver fibrosis in mice treated with carbon tetrachloride (CCl(4)). Transplantation of BMCs and concurrent treatment with FGF2 caused a statistically significant reduction in CCl(4)-induced liver fibrosis that was accompanied by strong expression of matrix metalloproteinase 9 as compared with FGF2-only treatment or BMT alone. Moreover, in this process, the proliferation of bone-marrow-derived cells was accelerated without causing apoptosis. Thus, the administration of FGF2 in combination with BMT synergistically improves CCl(4)-induced liver fibrosis in mice. This treatment has the potential of being an effective therapy for patients with liver cirrhosis.
- Published
- 2006
8. Status and prospects of liver cirrhosis treatment by using bone marrow-derived cells and mesenchymal cells
- Author
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Koichi Fujisawa, Yasuho Taura, Isao Sakaida, Ishikawa T, Tokiwa Yamasaki, Takuya Iwamoto, Kouichi Uchida, Isao Hidaka, Yohei Urata, Fujii Y, Marumoto M, Yoshio Marumoto, K Okita, Haruko Tanimoto, Naoki Yamamoto, G. R. Burganova, Kenji Tani, Takashi Oono, Shuji Terai, Taro Takami, T. Matsuda, Fernando Quintanilha L, Hiroshi Nishina, Yuko Mizunaga, and Issei Saeki
- Subjects
Liver Cirrhosis ,Pathology ,medicine.medical_specialty ,Cirrhosis ,Cellular differentiation ,Biomedical Engineering ,Bioengineering ,Bone Marrow Cells ,Mesenchymal Stem Cell Transplantation ,Biochemistry ,Peripheral blood mononuclear cell ,Gastroenterology ,Biomaterials ,Internal medicine ,medicine ,Animals ,Humans ,Local anesthesia ,Progenitor cell ,Vein ,Bone Marrow Transplantation ,Tissue Engineering ,business.industry ,Mesenchymal stem cell ,Cell Differentiation ,Mesenchymal Stem Cells ,medicine.disease ,Liver Regeneration ,medicine.anatomical_structure ,Bone marrow ,business ,Forecasting - Abstract
In 2003, we started autologous bone marrow cell infusion (ABMi) therapy for treating liver cirrhosis. ABMi therapy uses 400 mL of autologous bone marrow obtained under general anesthesia and infused mononuclear cells from the peripheral vein. The clinical study expanded and we treated liver cirrhosis induced by HCV and HBV infection and alcohol consumption. We found that the ABMi therapy was effective for cirrhosis patients and now we are treating patients with combined HIV and HCV infection and with metabolic syndrome-induced liver cirrhosis. Currently, to substantiate our findings that liver cirrhosis can be successfully treated by the ABMi therapy, we are conducting randomized multicenter clinical studies designated "Advanced medical technology B" for HCV-related liver cirrhosis in Japan. On the basis of our clinical study, we developed a proof-of-concept showing that infusion of bone marrow cells (BMCs) improved liver fibrosis and sequentially activated proliferation of hepatic progenitor cells and hepatocytes, further promoting restoration of liver functions. To treat patients with severe forms of liver cirrhosis, we continued translational research to develop less invasive therapies by using mesenchymal stem cells derived from bone marrow. We obtained a small quantity of BMCs under local anesthesia and expanded them into mesenchymal stem cells that will then be used for treating cirrhosis. In this review, we present our strategy to apply the results of our laboratory research to clinical studies. Copyright © 2014, Mary Ann Liebert, Inc.
- Published
- 2014
9. Hepatic Crown-Like Structure: A Unique Histological Feature in Non-Alcoholic Steatohepatitis in Mice and Humans
- Author
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Hiroshi Sakugawa, Seiichiro Aoe, Yoshihiro Komohara, Shuji Terai, Miho Hamaguchi, Yoshihiro Ogawa, Takahiro Fukaishi, Kuniha Konuma, Sayaka Kanai, Isao Sakaida, Yoshio Marumoto, Michiko Itoh, Takayoshi Suganami, Hideaki Kato, Motohiro Takeya, and Kazunari Akiyoshi
- Subjects
Liver Cirrhosis ,Male ,Pathology ,medicine.medical_specialty ,Hepatitis, Viral, Human ,Adipose tissue ,lcsh:Medicine ,Inflammation ,Biology ,Pathogenesis ,Mice ,Fibrosis ,Non-alcoholic Fatty Liver Disease ,medicine ,Animals ,Humans ,lcsh:Science ,Mice, Knockout ,Multidisciplinary ,Macrophages ,Fatty liver ,lcsh:R ,Lipid metabolism ,Middle Aged ,medicine.disease ,Lipid Metabolism ,Fatty Liver ,Mice, Inbred C57BL ,Phenotype ,Liver ,Chronic Disease ,Liposomes ,Receptor, Melanocortin, Type 4 ,lcsh:Q ,Female ,medicine.symptom ,Steatohepatitis ,Steatosis ,Clodronic Acid ,Research Article - Abstract
Although macrophages are thought to be crucial for the pathogenesis of chronic inflammatory diseases, how they are involved in disease progression from simple steatosis to non-alcoholic steatohepatitis (NASH) is poorly understood. Here we report the unique histological structure termed “hepatic crown-like structures (hCLS)” in the mouse model of human NASH; melanocortin-4 receptor deficient mice fed a Western diet. In hCLS, CD11c-positive macrophages aggregate to surround hepatocytes with large lipid droplets, which is similar to those described in obese adipose tissue. Histological analysis revealed that hCLS is closely associated with activated fibroblasts and collagen deposition. When treatment with clodronate liposomes effectively depletes macrophages scattered in the liver, with those in hCLS intact, hepatic expression of inflammatory and fibrogenic genes is unaffected, suggesting that hCLS is an important source of inflammation and fibrosis during the progression of NASH. Notably, the number of hCLS is positively correlated with the extent of liver fibrosis. We also observed increased number of hCLS in the liver of non-alcoholic fatty liver disease/NASH patients. Collectively, our data provide evidence that hCLS is involved in the development of hepatic inflammation and fibrosis, thereby suggesting its pathophysiologic role in disease progression from simple steatosis to NASH.
- Published
- 2013
10. Timeline for development of autologous bone marrow infusion (ABMi) therapy and perspective for future stem cell therapy
- Author
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Toshihiko Matsumoto, Koichi Fujisawa, Masaki Maeda, Masako Tsuchiya, Yuichiro Yokoyama, Yohei Urata, Isao Sakaida, Isao Hidaka, Takahiro Yamasaki, Kaoru Omori, Takuya Iwamoto, Makoto Segawa, Koichi Uchida, Shuji Terai, Tsuyoshi Ishikawa, Haruko Tanimoto, Kiwamu Okita, Yoshio Marumoto, Taro Takami, Takuro Hisanaga, Naoki Yamamoto, Koji Aoyama, Yuko Mizunaga, and Junichi Zaitsu
- Subjects
Liver Cirrhosis ,medicine.medical_specialty ,Cirrhosis ,Carcinoma, Hepatocellular ,medicine.medical_treatment ,Splenectomy ,Mesenchymal Stem Cell Transplantation ,Cell therapy ,Mice ,Granulocyte Colony-Stimulating Factor ,medicine ,Animals ,Humans ,Bone Marrow Transplantation ,business.industry ,Mesenchymal stem cell ,Liver Neoplasms ,Gastroenterology ,Stem-cell therapy ,medicine.disease ,Liver regeneration ,Surgery ,Liver Regeneration ,Disease Models, Animal ,medicine.anatomical_structure ,Bone marrow ,business ,Progressive disease - Abstract
Liver cirrhosis patients generally progress to liver failure. To cure this progressive disease, we developed a novel cell therapy using bone marrow cells; autologous bone marrow cell infusion (ABMi) therapy. We previously described the possible action mechanism of ABMi therapy in the cirrhotic liver, and showed the timeline and results of clinical studies of ABMi therapy. We have also carried out other clinical studies using bone marrow cells and granulocyte colony-stimulating factor. Here, we report a new randomized clinical trial to evaluate the effects of ABMi therapy. However, ABMi therapy may not be possible in patients who are unable to undergo general anesthesia; therefore, we have started to develop a next-generation stem cell therapy using cultured mesenchymal stem cells.
- Published
- 2012
11. Continuous high expression of XBP1 and GRP78 is important for the survival of bone marrow cells in CCl4-treated cirrhotic liver
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Toshihiko Matsumoto, Yoshio Marumoto, Yuko Mizunaga, Naoki Yamamoto, Koichi Fujisawa, Haiyan Jin, Hiroshi Nishina, Koh Shinoda, Tomoaki Murata, Isao Sakaida, Yohei Urata, and Shuji Terai
- Subjects
X-Box Binding Protein 1 ,Cirrhosis ,XBP1 ,Cell Survival ,Blotting, Western ,Biophysics ,Gene Expression ,CCL4 ,Bone Marrow Cells ,Mice, Transgenic ,Regulatory Factor X Transcription Factors ,Biology ,Liver Cirrhosis, Experimental ,Biochemistry ,Andrology ,Mice ,Cytochrome P-450 Enzyme System ,Gene expression ,medicine ,Animals ,HSP90 Heat-Shock Proteins ,Molecular Biology ,Carbon Tetrachloride ,Endoplasmic Reticulum Chaperone BiP ,Heat-Shock Proteins ,Bone Marrow Transplantation ,Endoplasmic reticulum ,Gene Expression Profiling ,Nuclear Proteins ,Cell Differentiation ,Cell Biology ,HSP40 Heat-Shock Proteins ,medicine.disease ,Immunohistochemistry ,humanities ,Gene expression profiling ,DNA-Binding Proteins ,Mice, Inbred C57BL ,Disease Models, Animal ,Microscopy, Electron ,medicine.anatomical_structure ,Hepatocyte ,Immunology ,Disease Progression ,Female ,Bone marrow ,Molecular Chaperones ,Transcription Factors - Abstract
We have previously shown that infusion of bone marrow cells (BMC) improves CCl 4 -induced cirrhosis. However, it is unclear why the injected BMC are resistant to CCl 4 damage and subsequently improve the local microenvironment in damaged liver. To analyze the cellular phenomena involved in this process, we studied the damaged liver using electron microscopy. We found that CCl 4 caused rough endoplasmic reticula to swell in hepatocytes. To analyze the gene expression patterns associated with this process, we conducted PCR-selected suppressive subtractive hybridization. We found that expression levels of HSP84, HSP40, and XBP1 differed markedly between control liver and liver infused with BMC. Immunohistochemical staining revealed that expression levels of HSP84 and HSP40 were markedly higher in the early phase of differentiation immediately after BMC infusion, but decreased over time. XBP1 expression remained high during the late phase, and GRP78 expression increased with XBP1 activation. We also found that GFP-positive BMC expressed XBP1 and GRP78. XBP1 and GRP78 are associated with ER stress. Thus, continuous high XBP1 and GRP78 expression might be essential for the survival and proliferation of BMC in a CCl 4 -induced persistent liver damage environment.
- Published
- 2007
12. Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy
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Yuichirou Yokoyama, Takahiro Yamasaki, Koji Aoyama, Kaoru Omori, Kiwamu Okita, Tsuyoshi Ishikawa, Shuji Terai, Yasuhiko Fujii, Isao Sakaida, Yoshio Marumoto, Yohei Urata, and Koichi Uchida
- Subjects
Liver Cirrhosis ,Male ,medicine.medical_specialty ,Cirrhosis ,Antigens, CD34 ,Bone Marrow Cells ,Biology ,Peripheral blood mononuclear cell ,Gastroenterology ,Transplantation, Autologous ,Monocytes ,Infusion therapy ,Internal medicine ,Proliferating Cell Nuclear Antigen ,medicine ,Humans ,Aged ,Bone Marrow Transplantation ,medicine.diagnostic_test ,Cell Biology ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Liver regeneration ,Transplantation ,Proto-Oncogene Proteins c-kit ,Treatment Outcome ,Liver ,Liver biopsy ,Hepatocellular carcinoma ,Immunology ,Molecular Medicine ,Leukocyte Common Antigens ,Female ,Liver function ,alpha-Fetoproteins ,Developmental Biology ,Follow-Up Studies - Abstract
We here report nine liver cirrhosis (LC) patients that underwent autologous bone marrow cell infusion (ABMI) from the peripheral vein. Subjects were patients with LC with total bilirubin of less than 3.0 mg/dl, platelet count of more than 5 (10(10)/l), and no viable hepatocellular carcinoma on diagnostic imaging. Autologous bone marrow (BM; 400 ml) was isolated from the ilium under general anesthesia. Mononuclear cells (MNCs) were separated by cell washing and were infused via the peripheral vein. MNC characteristics were confirmed by fluorescence-activated cell sorting analysis (CD34, CD45, and c-kit). After ABMI therapy, liver function was monitored by blood examination for 24 weeks. From 400 ml of BM, we obtained 7.81 +/- 0.98 x 10(9) MNCs. After washing, 5.20 +/- 0.63 x 10(9) MNCs were infused into patients with LC. Significant improvements in serum albumin levels and total protein were observed at 24 weeks after ABMI therapy (p < .05). Significantly improved Child-Pugh scores were seen at 4 and 24 weeks (p < .05). alpha-Fetoprotein and proliferating cell nuclear antigen (PCNA) expression in liver biopsy tissue was significantly elevated after ABMI therapy (p < .05). No major adverse effects were noted. In conclusion, ABMI therapy should be considered as a novel treatment for patients with decompensated LC.
- Published
- 2006
13. Proteomic analysis of serum marker proteins in recipient mice with liver cirrhosis after bone marrow cell transplantation
- Author
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Yuichiro Yokoyama, Yohei Urata, Yoshio Marumoto, Kazuyuki Nakamura, Shuji Terai, Tsuyoshi Ishikawa, Koji Aoyama, Kiwamu Okita, Hiroshi Nishina, and Isao Sakaida
- Subjects
musculoskeletal diseases ,Liver Cirrhosis ,Proteomics ,medicine.medical_specialty ,Proteasome Endopeptidase Complex ,Cirrhosis ,Apolipoprotein B ,Vitamin D-binding protein ,Biochemistry ,Mice ,Cell Movement ,Internal medicine ,medicine ,Animals ,Regeneration ,Apolipoproteins C ,Molecular Biology ,Carbon Tetrachloride ,Bone Marrow Transplantation ,biology ,Apolipoprotein A-I ,Vitamin D-Binding Protein ,Albumin ,Proteins ,musculoskeletal system ,medicine.disease ,humanities ,Liver regeneration ,Transplantation ,Endocrinology ,medicine.anatomical_structure ,Liver ,alpha 1-Antitrypsin ,Immunology ,biology.protein ,Liver function ,Bone marrow - Abstract
We previously found that transplantation with bone marrow cells (BMCs) improves liver function and liver fibrosis in cirrhotic mice. In the presence of liver damage induced by carbon tetrachloride (CCl4), transplanted BMC migrated into the peri-portal region and trans-differentiated into hepatocytes that produce albumin. Thus under these conditions, BMC transplantation induces liver regeneration. Detecting serum marker proteins is important to monitor the recovery of liver function of cirrhotic mice after BMC transplantation. We therefore initially resolved proteins extracted from serum samples at 48 h after BMC transplantation by 2-DE and compared spot intensity between control and BMC groups of mice. Six protein spots increased in the BMC group compared with the control group. MS revealed that these spots comprised apolipoprotein A1 (apoA1), apolipoprotein C3 (apoC3), vitamin D-binding protein, alpha-1-antitrypsin and proteasome subunit alpha type 1. We subsequently confirmed the levels of apoA1 in serum and liver samples by immunoblotting. ApoA1 increased at early stage (48 h and 1 wk) after BMC transplantation in this mouse model of liver cirrhosis. The early elevation of apoA1 might be useful to predict liver regeneration in cirrhotic mice after BMC transplantation.
- Published
- 2006
14. Fibroblast growth factor 2 facilitates the differentiation of transplanted bone marrow cells into hepatocytes
- Author
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Shunji Uchimura, Yohei Urata, Isao Sakaida, Yoshio Marumoto, Koh Shinoda, Koji Aoyama, Tomoaki Murata, Yoshihiko Hamamoto, Shuji Terai, Tsuyoshi Ishikawa, Hiroshi Nishina, and Kiwamu Okita
- Subjects
medicine.medical_specialty ,Histology ,medicine.medical_treatment ,Green Fluorescent Proteins ,Bone Marrow Cells ,Biology ,Fibroblast growth factor ,Liver Cirrhosis, Experimental ,Pathology and Forensic Medicine ,Mice ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,Carbon Tetrachloride ,Bone Marrow Transplantation ,Oligonucleotide Array Sequence Analysis ,Fibroblast growth factor receptor 1 ,Growth factor ,Cell Differentiation ,Cell Biology ,FGF1 ,Immunohistochemistry ,Recombinant Proteins ,Transplantation ,Mice, Inbred C57BL ,Disease Models, Animal ,Endocrinology ,medicine.anatomical_structure ,Hepatocyte ,Cancer research ,Hepatocytes ,Female ,Fibroblast Growth Factor 2 ,Liver function ,Bone marrow ,Signal Transduction - Abstract
We have developed an in vivo mouse model, the green fluorescent protein (GFP)/carbon tetrachloride (CCl(4)) model, and have previously reported that transplanted GFP-positive bone marrow cells (BMCs) differentiate into hepatocytes via hepatoblast intermediates. Here, we have investigated the growth factors that are closely related to the differentiation of transplanted BMCs into hepatocytes, and the way that a specific growth factor affects the differentiation process in the GFP/CCl(4) model. We performed immunohistochemical analysis to identify an important growth factor in our model, viz., fibroblast growth factor (FGF). In liver samples, the expression of FGF1 and FGF2 and of FGF receptors (FGFRs; FGFR1, FGFR2) was significantly elevated with time after bone marrow transplantation (BMT) compared with other factors, and co-expression of GFP and FGFs or FGFRs could be detected. We then analyzed the effect and molecular mechanism of FGF signaling on the enhancement of BMC differentiation into hepatocytes by immunohistochemistry, immunoblotting, and microarray analysis. Treatment with recombinant FGF (rFGF), especially rFGF2, elevated the repopulation rate of GFP-positive cells in the liver and significantly increased the expression of both Liv2 (hepatoblast marker) and albumin (hepatocyte marker). Administration of rFGF2 at BMT also raised serum albumin levels and improved the survival rate. Transplantation of BMCs with rFGF2 specifically activated tumor necrosis factor-alpha (TNF-alpha) signaling. Thus, FGF2 facilitates the differentiation of transplanted BMCs into albumin-producing hepatocytes via Liv2-positive hepatoblast intermediates through the activation of TNF-alpha signaling. Administration of FGF2 in combination with BMT improves the liver function and prognosis of mice with CCl(4)-induced liver damage.
- Published
- 2005
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