慶應義塾研究者情報データベース

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• Modeling Mitochondrial Disease Using Brain Organoids: A Focus on Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes

  Kawano S., Saegusa C., Masano Y., Becker F., Nakamura M., Shiozawa S., Fujikura J., Toyohara T., Abe T., Okano H., Fujioka M.

  Journal of Visualized Experiments 2025 October （ 224 ）  2025年10月

  ISSN  1940087X

  　概要を見る

  Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) are mitochondrial disorders most commonly caused by a m.3243A>G variant in mitochondrial tRNA^Leu . To investigate the pathophysiology of MELAS, we generated brain organoids from multiple induced pluripotent stem cell (iPSC) lines derived from a patient with MELAS carrying the m.3243A>G variant. These lines share an identical nuclear genetic background but differ in their heteroplasmy levels involving the m.3243A>G variant. We observed significant differences in organoid size, morphology, and neural induction efficiency, which correlated with the degree of heteroplasmy. Dissociated neurons from the organoids were transferred into a 2D-culture system, which is convenient and suitable for high-throughput drug screening. The organoids also exhibited significant differences in the formation of neural networks, depending on heteroplasmy levels. Our results suggest that patient-derived iPSC-based organoid models represent a useful platform for studying MELAS mechanisms and for drug screening. This video presents comprehensive and user-friendly methods, including protocols for generating organoids and evaluating phenotypes.

  • Access to Document (DOI)

• Attempts for deriving extended pluripotent stem cells from common marmoset embryonic stem cells

  Yoshimatsu S., Nakajima M., Sonn I., Natsume R., Sakimura K., Nakatsukasa E., Sasaoka T., Nakamura M., Serizawa T., Sato T., Sasaki E., Deng H., Okano H.

  Genes to Cells 28 （ 2 ） 156 - 169 2023年02月

  ISSN  13569597

  　概要を見る

  Extended pluripotent stem cells (EPSCs) derived from mice and humans showed an enhanced potential for chimeric formation. By exploiting transcriptomic approaches, we assessed the differences in gene expression profile between extended EPSCs derived from mice and humans, and those newly derived from the common marmoset (marmoset; Callithrix jacchus). Although the marmoset EPSC-like cells displayed a unique colony morphology distinct from murine and human EPSCs, they displayed a pluripotent state akin to embryonic stem cells (ESCs), as confirmed by gene expression and immunocytochemical analyses of pluripotency markers and three-germ-layer differentiation assay. Importantly, the marmoset EPSC-like cells showed interspecies chimeric contribution to mouse embryos, such as E6.5 blastocysts in vitro and E6.5 epiblasts in vivo in mouse development. Also, we discovered that the perturbation of gene expression of the marmoset EPSC-like cells from the original ESCs resembled that of human EPSCs. Taken together, our multiple analyses evaluated the efficacy of the method for the derivation of marmoset EPSCs.

  • Access to Document (DOI)

• Non-viral Induction of Transgene-free iPSCs from Somatic Fibroblasts of Multiple Mammalian Species

  Yoshimatsu S., Nakajima M., Iguchi A., Sanosaka T., Sato T., Nakamura M., Nakajima R., Arai E., Ishikawa M., Imaizumi K., Watanabe H., Okahara J., Noce T., Takeda Y., Sasaki E., Behr R., Edamura K., Shiozawa S., Okano H.

  Stem Cell Reports 16 （ 4 ） 754 - 770 2021年04月

  ISSN  22136711

  　概要を見る

  Induced pluripotent stem cells (iPSCs) are capable of providing an unlimited source of cells from all three germ layers and germ cells. The derivation and usage of iPSCs from various animal models may facilitate stem cell-based therapy, gene-modified animal production, and evolutionary studies assessing interspecies differences. However, there is a lack of species-wide methods for deriving iPSCs, in particular by means of non-viral and non-transgene-integrating (NTI) approaches. Here, we demonstrate the iPSC derivation from somatic fibroblasts of multiple mammalian species from three different taxonomic orders, including the common marmoset (Callithrix jacchus) in Primates, the dog (Canis lupus familiaris) in Carnivora, and the pig (Sus scrofa) in Cetartiodactyla, by combinatorial usage of chemical compounds and NTI episomal vectors. Interestingly, the fibroblasts temporarily acquired a neural stem cell-like state during the reprogramming. Collectively, our method, robustly applicable to various species, holds a great potential for facilitating stem cell-based research using various animals in Mammalia.

  • Access to Document (DOI)

• Glucocorticoid regulation of proteoglycan synthesis in mesangial cells

  Kuroda Mari, Sasamura Hiroyuki, Shimizu-Hirota Ryoko, Mifune Mizuo, Nakaya Hideaki, Kobayashi Emi, Hayashi Matsuhiko, Saruta Takao

  Kidney international 62 （ 3 ） 780-789 2002年09月

  研究論文（学術雑誌）, 共著

• Prepubertal treatment with angiotensin receptor blocker causes partial attenuation of hypertension and renal damage in adult Dahl salt-sensitive rats

  Nakaya Hideaki, Sasamura Hiroyuki, Mifune Mizuo, Shimizu-Hirota Ryoko, Kuroda Mari, Hayashi Matsuhiko, Saruta Takao

  Nephron 91 （ 4 ） 710-718 2002年08月

  研究論文（学術雑誌）, 共著

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KOARA（リポジトリ）収録論文等 【 表示 ／ 非表示 】

KOARA（リポジトリ）収録論文等 【 表示 ／ 非表示 】

• 糖質コルチコイドによるメサンギウム細胞のプロテオグリカン産生の調節

  中村, 真理

  慶應医学 （慶應医学会）  81 （ 4 ） 31 2004年12月

  ISSN  03685179

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• アンジオテンシンIIの一過性阻害による高血圧性腎硬化症持続抑制の試み

  中谷英章，篠村裕之，清水良子，黒田真理，小林絵美，林松彦，猿田享男

  [国内会議]  第8回アンジオテンシンカンファレンス, 

  2003年02月

  , 

  口頭発表（一般）

• アンジオテンシンII(AII)による細胞外基質プロテオグリカン発現調節の検討

  清水良子，篠村裕之，中谷英章，三船瑞夫，黒田真理，小林絵美，林松彦，猿田享男

  [国内会議]  第7回アンジオテンシンカンファレンス, 

  2002年02月

• Dexamethasone regulates glycosaminoglycan synthesis and proteoglycan core protein gene expression in rat and human mesangial cells

  Kuroda Mari, Sasamura Hiroyuki, Mizuo Mifune, Shimizu-Hirota Ryoko, Nakaya Hideaki, Kobayashi Emi, Hayashi Matsuhiko, Saruta Takao

  [国際会議]  Annual Meeting of American Society of Nephrology (34th ; 2001 ; San Francisco, CA, USA), 

  2001年10月

• Effects of prepubertal treatment with angiotensin receptor blocker (ARB) on hypertension and end-organ damage in adult Dahl salt-sensitive rats

  Nakaya Hideaki, Sasamura Hiroyuki, Mifune Mizuo, Shimizu-Hirota Ryoko, Kuroda Mari, Kobayashi Emi, Hayashi Matsuhiko, Saruta Takao

  [国際会議]  Annual Meeting of American Society of Nephrology (34th ; 2001 ; San Francisco, CA, USA), 

  2001年10月

• Angiotensin II type 2 (AT2) receptors regulate extracellular matrix proteoglycan synthesis by Galphai/o-dependent mechanisms

  Shimizu-Hirota Ryoko, Sasamura Hiroyuki, Mifune Mizuo, Nakaya Hideaki, Kuroda Mari, Kobayashi Emi, Hayashi Matsuhiko, Saruta Takao

  [国際会議]  Annual Meeting of American Society of Nephrology (34th ; 2001 ; San Francisco, CA, USA), 

  2001年10月

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担当授業科目 【 表示 ／ 非表示 】

担当授業科目 【 表示 ／ 非表示 】

• 現代社会と医学Ⅱ

  2026年度

• 現代社会と医学Ⅰ

  2026年度

• 現代社会と医学Ⅱ

  2025年度

• 現代社会と医学Ⅰ

  2025年度

• 現代社会と医学Ⅰ

  2024年度