{"_buckets": {"deposit": "a42ac86c-17ce-4144-984c-aacd78749880"}, "_deposit": {"id": "34002", "owners": [], "pid": {"revision_id": 0, "type": "depid", "value": "34002"}, "status": "published"}, "_oai": {"id": "oai:niigata-u.repo.nii.ac.jp:00034002", "sets": ["455", "562"]}, "item_6_alternative_title_1": {"attribute_name": "その他のタイトル", "attribute_value_mlt": [{"subitem_alternative_title": "通常酸素条件下よりも低酸素条件下で培養した間葉系幹細胞の方が肝硬変マウスに対してより大きな治療効果を認めた"}]}, "item_6_date_granted_51": {"attribute_name": "学位授与年月日", "attribute_value_mlt": [{"subitem_dategranted": "2020-03-23"}]}, "item_6_degree_grantor_49": {"attribute_name": "学位授与機関", "attribute_value_mlt": [{"subitem_degreegrantor": [{"subitem_degreegrantor_name": "新潟大学"}]}]}, "item_6_degree_name_48": {"attribute_name": "学位名", "attribute_value_mlt": [{"subitem_degreename": "博士(医学)"}]}, "item_6_description_4": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "Background: Mesenchymal stem cells (MSCs) can be easily expanded. They can be acquired from medical waste such as adipose and umbilical cord tissues, are influenced by culturing conditions, and exert anti-inflammatory, antioxidant, anti-fibrotic, and angiogenic effects. We analyzed the multi-directional effects of MSCs cultured under hypoxic conditions and their underlying mechanisms in the treatment of liver cirrhosis in a mouse model. Methods: Human bone marrow-derived MSCs cultured under hypoxic (5% O_2; hypoMSCs) and normoxic (21% O_2; norMSCs) conditions were compared by cap analysis of gene expression (CAGE) with or without serum from liver cirrhosis patients. The therapeutic effects of MSCs, including serum liver enzyme induction, fibrosis regression, and hepatic oxidative stress, were evaluated by injecting 1×10^6, 2×10^5, or4 10^4 MSCs/mouse into the tail veins of mice with carbon tetrachloride (CCl_4) -induced liver cirrhosis. Intravital imaging was performed with a two-photon excitation microscope to confirm the various MSC migration paths to the liver. Results: CAGE analysis revealed that the RNA expression levels of prostaglandin E synthase (Ptges) and miR210 were significantly higher in hypoMSCs than in norMSCs. In vivo analysis revealed that both hypoMSCs and norMSCs reduced serum alanine aminotransferase, oxidative stress, and fibrosis compared to that in control mice in a dose-dependent manner. However, hypoMSCs had stronger therapeutic effects than norMSCs. We confirmed this observation by an in vitro study in which hypoMSCs changed macrophage polarity to an anti-inflammatory phenotype via prostaglandin E2 (PGE2) stimulation. In addition, miR210 reduced the rate of hepatocyte apoptosis. Intravital imaging after MSC administration showed that both cell types were primarily trapped in the lungs. Relatively a fewhypoMSCs and norMSCs migrated to the liver. There were no significant differences in their distributions. Conclusion: The therapeutic effect of hypoMSCs was mediated by PGE2 and miR210 production and was greater than that of norMSCs. Therefore, MSCs can be manipulated to improve their therapeutic efficacy in the treatment of liver cirrhosis and could potentially serve in effective cell therapy. MSCs produce several factors with multidirectional effects and function as “conducting cells” in liver cirrhosis.", "subitem_description_type": "Abstract"}]}, "item_6_description_5": {"attribute_name": "内容記述", "attribute_value_mlt": [{"subitem_description": "Regenerative Therapy. 2019, 11, 269-281.", "subitem_description_type": "Other"}]}, "item_6_description_53": {"attribute_name": "学位記番号", "attribute_value_mlt": [{"subitem_description": "新大院博(医)甲第911号", "subitem_description_type": "Other"}]}, "item_6_dissertation_number_52": {"attribute_name": "学位授与番号", "attribute_value_mlt": [{"subitem_dissertationnumber": "13101甲第4677号"}]}, "item_6_full_name_3": {"attribute_name": "著者別名", "attribute_value_mlt": [{"nameIdentifiers": [{"nameIdentifier": "178004", "nameIdentifierScheme": "WEKO"}], "names": [{"name": "小島, 雄一"}]}]}, "item_6_relation_14": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_type_id": {"subitem_relation_type_id_text": "info:doi/10.1016/j.reth.2019.08.005", "subitem_relation_type_select": "DOI"}}]}, "item_6_rights_15": {"attribute_name": "権利", "attribute_value_mlt": [{"subitem_rights": "【○!C】 2019, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)."}]}, "item_6_select_19": {"attribute_name": "著者版フラグ", "attribute_value_mlt": [{"subitem_select_item": "ETD"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Kojima, Yuichi"}], "nameIdentifiers": [{"nameIdentifier": "178003", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2020-08-31"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "r1nmk911.pdf", "filesize": [{"value": "3.3 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_free", "mimetype": "application/pdf", "size": 3300000.0, "url": {"label": "本文", "url": "https://niigata-u.repo.nii.ac.jp/record/34002/files/r1nmk911.pdf"}, "version_id": "59abb0c8-1edd-4e76-909c-258f71d90bf9"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2020-08-31"}], "displaytype": "detail", "download_preview_message": "", "file_order": 1, "filename": "r1nmk911_a.pdf", "filesize": [{"value": "576.7 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_free", "mimetype": "application/pdf", "size": 576700.0, "url": {"label": "要旨", "url": "https://niigata-u.repo.nii.ac.jp/record/34002/files/r1nmk911_a.pdf"}, "version_id": "a5f0f1d4-885a-4103-b8fb-a4247e732199"}]}, "item_keyword": {"attribute_name": "キーワード", "attribute_value_mlt": [{"subitem_subject": "Mesenchymal stem cells", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Hypoxic condition", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Liver cirrhosis", "subitem_subject_scheme": "Other"}, {"subitem_subject": "PGE2", "subitem_subject_scheme": "Other"}, {"subitem_subject": "miR210", "subitem_subject_scheme": "Other"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "thesis", "resourceuri": "http://purl.org/coar/resource_type/c_46ec"}]}, "item_title": "Mesenchymal stem cells cultured under hypoxic conditions had a greater therapeutic effect on mice with liver cirrhosis compared to those cultured under normal oxygen conditions", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Mesenchymal stem cells cultured under hypoxic conditions had a greater therapeutic effect on mice with liver cirrhosis compared to those cultured under normal oxygen conditions"}]}, "item_type_id": "6", "owner": "1", "path": ["455", "562"], "permalink_uri": "http://hdl.handle.net/10191/00051800", "pubdate": {"attribute_name": "公開日", "attribute_value": "2020-08-31"}, "publish_date": "2020-08-31", "publish_status": "0", "recid": "34002", "relation": {}, "relation_version_is_last": true, "title": ["Mesenchymal stem cells cultured under hypoxic conditions had a greater therapeutic effect on mice with liver cirrhosis compared to those cultured under normal oxygen conditions"], "weko_shared_id": null}