KEIO RESEARCHERS INFORMATION SYSTEM

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• 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 )  2025.10

  ISSN  1940087X

  　View Summary

  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 2023.02

  ISSN  13569597

  　View Summary

  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 2021.04

  ISSN  22136711

  　View Summary

  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 2002.09

  Research paper (scientific journal), Joint Work

• 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 2002.08

  Research paper (scientific journal), Joint Work

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Papers, etc., Registered in KOARA 【 Display / hide 】

Papers, etc., Registered in KOARA 【 Display / hide 】

• Glucocorticoid regulation of proteoglycan synthesis in mesangial cells .

  中村, 真理

  Journal of the Keio Medical Society (慶應医学会)  81 ( 4 ) 31 2004.12

  ISSN  03685179

Presentations 【 Display / hide 】

Presentations 【 Display / hide 】

• 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

  Nakaya Hideaki, Sasamura Hiroyuki, Shimizu Ryouko, Kuroda Mari, Kobayashi Emi, Hayashi Matsuhiko, Saruta Takao

  [Domestic presentation]  第8回アンジオテンシンカンファレンス, 

  2003.02

  , 

  Oral presentation (general)

• 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

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

  [Domestic presentation]  第7回アンジオテンシンカンファレンス, 

  2002.02

• 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

  [International presentation]  Annual Meeting of American Society of Nephrology (34th ; 2001 ; San Francisco, CA, USA), 

  2001.10

• 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

  [International presentation]  Annual Meeting of American Society of Nephrology (34th ; 2001 ; San Francisco, CA, USA), 

  2001.10

• 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

  [International presentation]  Annual Meeting of American Society of Nephrology (34th ; 2001 ; San Francisco, CA, USA), 

  2001.10

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Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• MEDICINE IN MODERN SOCIETY 2

  2026

• MEDICINE IN MODERN SOCIETY 1

  2026

• MEDICINE IN MODERN SOCIETY 2

  2025

• MEDICINE IN MODERN SOCIETY 1

  2025

• MEDICINE IN MODERN SOCIETY 1

  2024