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Fatty Acid-Treated Induced Pluripotent Stem Cell-Derived Human Cardiomyocytes Exhibit Adult Cardiomyocyte-Like Energy Metabolism Phenotypes
https://asahikawa-med.repo.nii.ac.jp/records/6258
https://asahikawa-med.repo.nii.ac.jp/records/6258ac23910d-c757-4d0b-af02-095c54ce3098
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
7550.pdf (12.1 MB)
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| Item type | 学位論文 / Thesis or Dissertation_02(1) | |||||
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| 公開日 | 2021-04-23 | |||||
| タイトル | ||||||
| タイトル | Fatty Acid-Treated Induced Pluripotent Stem Cell-Derived Human Cardiomyocytes Exhibit Adult Cardiomyocyte-Like Energy Metabolism Phenotypes | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | cardiomyocytes | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | induced pluripotent stem cells | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | maturation | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | metabolism | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
| 資源タイプ | doctoral thesis | |||||
| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| その他（別言語等）のタイトル | ||||||
| その他のタイトル | iPS細胞由来心筋細胞は、脂肪酸処理によって成熟心筋細胞様のエネルギー代謝へ変化する | |||||
| 言語 | ja | |||||
| 著者 |
堀越, 佑一
× 堀越, 佑一 |
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| 著者 ローマ字 | ||||||
| 値 | Horikoshi, Yuichi | |||||
| 書誌情報 |
Cells 巻 8, 号 9, p. 1095, 発行日 2019-09-01 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 2073-4409 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.3390/cells8091095 | |||||
| 識別番号 その他 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | PMID: 31533262 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲541 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2020-03-25 | |||||
| 学位名 | ||||||
| 学位名 | 博士（医学） | |||||
| 学位授与機関 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 10107 | |||||
| 学位授与機関名 | 旭川医科大学 | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) (iPSC-CMs) are a promising cell source for myocardial regeneration, disease modeling and drug assessment. However, iPSC-CMs exhibit immature fetal CM-like characteristics that are different from adult CMs in several aspects, including cellular structure and metabolism. As an example, glycolysis is a major energy source for immature CMs. As CMs mature, the mitochondrial oxidative capacity increases, with fatty acid β-oxidation becoming a key energy source to meet the heart's high energy demand. The immaturity of iPSC-CMs thereby limits their applications. The aim of this study was to investigate whether the energy substrate fatty acid-treated iPSC-CMs exhibit adult CM-like metabolic properties. After 20 days of differentiation from human iPSCs, iPSC-CMs were sequentially cultured with CM purification medium (lactate+/glucose-) for 7 days and maturation medium (fatty acids+/glucose-) for 3-7 days by mimicking the adult CM's preference of utilizing fatty acids as a major metabolic substrate. The purity and maturity of iPSC-CMs were characterized via the analysis of: (1) Expression of CM-specific markers (e.g., troponin T, and sodium and potassium channels) using RT-qPCR, Western blot or immunofluorescence staining and electron microscopy imaging; and (2) cell energy metabolic profiles using the XF96 Extracellular Flux Analyzer. iPSCs-CMs (98% purity) cultured in maturation medium exhibited enhanced elongation, increased mitochondrial numbers with more aligned Z-lines, and increased expression of matured CM-related genes, suggesting that fatty acid-contained medium promotes iPSC-CMs to undergo maturation. In addition, the oxygen consumption rate (OCR) linked to basal respiration, ATP production, and maximal respiration and spare respiratory capacity (representing mitochondrial function) was increased in matured iPSC-CMs. Mature iPSC-CMs also displayed a larger change in basal and maximum respirations due to the utilization of exogenous fatty acids (palmitate) compared with non-matured control iPSC-CMs. Etomoxir (a carnitine palmitoyltransferase 1 inhibitor) but not 2-deoxyglucose (an inhibitor of glycolysis) abolished the palmitate pretreatment-mediated OCR increases in mature iPSC-CMs. Collectively, our data demonstrate for the first time that fatty acid treatment promotes metabolic maturation of iPSC-CMs (as evidenced by enhanced mitochondrial oxidative function and strong capacity of utilizing fatty acids as energy source). These matured iPSC-CMs might be a promising human CM source for broad biomedical application. | |||||
| 資源タイプ | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| フォーマット | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
