Education 【 display / non-display 】

Education 【 display / non-display 】

• 2014

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  2018

  Sapporo Medical University   Graduate School of Medicine   解剖学第二講座  

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  博士課程

• 2012

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  2014

  Sapporo Medical University   Graduate School of Health Sciences  

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  博士課程前期

Degree 【 display / non-display 】

Degree 【 display / non-display 】

• 2018.03   札幌医科大学   博士 (医学)

• 2014.03   札幌医科大学   修士 (理学療法学)

Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2021.06

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  Now

  Sapporo Medical University   医学部 解剖学第二講座   講師

• 2019.09

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  2021.06

  Sapporo Medical University   School of Medicine, Department of Anatomy   助教

• 2019.07

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  2019.08

  Sapporo Medical University   School of Medicine, Department of Anatomy   特任助教

  特任助教

• 2018.06

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  2019.06

  Mayo Clinic   Department of Orthopedic Surgery,Tendon & Soft Tissue Biology Laboratory   Post doctoral fellow

  Post doctoral fellow

Professional Memberships 【 display / non-display 】

Professional Memberships 【 display / non-display 】

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  International Cell Senescence Association

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  Orthopedic Research Society

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  日本炎症・再生医学会

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  日本解剖学会

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  日本再生医療学会

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Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Sports science  

• Life sciences   Rehabilitation science  

• Life sciences   Orthopedics  

• Life sciences   Anatomy  

• Life sciences   Nutrition and health science  

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   解剖学第二講座   講師  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• Chronic Inflammation

• Regenerative medicine

• Fibrosis

• 間葉系幹細胞

• Rehabilitation

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Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Role of cellular senescence in inflammation and regeneration

  Yuki Saito, Sena Yamamoto, Takako S. Chikenji

  Inflammation and Regeneration ( Springer Science and Business Media LLC )  44 ( 1 )  2024.06  [Refereed]  [Invited]

  Authorship：   Lead author

  　View Summary

  Abstract Cellular senescence is the state in which cells undergo irreversible cell cycle arrest and acquire diverse phenotypes. It has been linked to chronic inflammation and fibrosis in various organs as well as to individual aging. Therefore, eliminating senescent cells has emerged as a potential target for extending healthy lifespans. Cellular senescence plays a beneficial role in many biological processes, including embryonic development, wound healing, and tissue regeneration, which is mediated by the activation of stem cells. Therefore, a comprehensive understanding of cellular senescence, including both its beneficial and detrimental effects, is critical for developing safe and effective treatment strategies to target senescent cells. This review provides an overview of the biological and pathological roles of cellular senescence, with a particular focus on its beneficial or detrimental functions among its various roles.

  DOI

• Senescence-associated secretory phenotypes in mesenchymal cells contribute to cytotoxic immune response in oral lichen planus.

  Shogo Ijima, Yuki Saito, Sena Yamamoto, Kentaro Nagaoka, Taiki Iwamoto, Arisa Kita, Maki Miyajima, Tsukasa Sato, Akihiro Miyazaki, Takako S Chikenji

  Immunity & ageing : I & A   20 ( 1 ) 72 - 72  2023.12  [Refereed]  [International journal]

  Authorship：   Corresponding author

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  Oral lichen planus is a chronic inflammatory condition that adversely affects the oral mucosa; however, its etiology remains elusive. Consequently, therapeutic interventions for oral lichen planus are limited to symptomatic management. This study provides evidence of the accumulation of senescent mesenchymal cells, CD8 + T cells, and natural killer cells in patients with oral lichen planus. We profiled the patients' tissues using the National Center for Biotechnology Information Gene Expression Omnibus database and found that senescence-related genes were upregulated in these tissues by gene set enrichment analysis. Immunohistochemical analysis showed increased senescent mesenchymal cells in the subepithelial layer of patients with oral lichen planus. Single-cell RNA-seq data retrieved from the Gene Expression Omnibus database of patients with oral lichen planus revealed that mesenchymal cells were marked by the upregulation of senescence-related genes. Cell-cell communication analysis using CellChat showed that senescent mesenchymal cells significantly influenced CD8 + T cells and natural killer cells via CXCL12-CXCR4 signaling, which is known to activate and recruit CD8 + T cells and NK cells. Finally, in vitro assays demonstrated that the secretion of senescence-associated factors from mesenchymal cells stimulated the activation of T cells and natural killer cells and promoted epithelial cell senescence and cytotoxicity. These findings suggest that the accumulation of mesenchymal cells with senescence-associated secretory phenotype may be a key driver of oral lichen planus pathogenesis.

  DOI PubMed

• Intrathecal Injection of Mesenchymal Stromal Cell Cultured on 3D Fiber Ameliorates Multiple Organ Damage in Murine Lupus

  Yuki Saito, Maki Miyajima, Sena Yamamoto, Norihiro Miura, Tsukasa Sato, Arisa Kita, Shogo Ijima, Mineko Fujimiya, Takako S Chikenji

  Stem Cells Translational Medicine ( Oxford University Press (OUP) )   2022.04  [Refereed]

  Authorship：   Lead author

  　View Summary

  Abstract Up to 60% of patients with systemic lupus erythematosus (SLE) experience autonomic symptom. Sympathetic nervous system damage can cause dysfunction of the bone marrow that activates inflammatory cells, potentially causing multiple organ damage. We hypothesized that sympathetic nervous system damage would induce bone marrow dysfunction with multiple organ damage in SLE, and that multiple organ damage could be improved by therapy targeting the nervous system. Here, we showed that damage to autonomic nerves and Schwann cells occurred in the bone marrow and central nervous system of SLE model mice. A neurotoxic drug increased mortality and induced severe neuropathy and multiple organ damage, while a neuroprotective drug prevented multiple organ damage. The administration of bone marrow-derived mesenchymal stromal cells (BMSCs) cultured on a 3-dimensional fiber scaffold improved bone marrow neuropathy, skin lesions, kidney function, and mortality. Our results reveal that bone marrow neuropathy influence multiple organ damage associated with SLE, and improvement of bone marrow neuropathy by intrathecal injection of BMSC may be a target for SLE multiple-organ damage.

  DOI

• Altered regulation of mesenchymal cell senescence in adipose tissue promotes pathological changes associated with diabetic wound healing.

  Arisa Kita, Yuki Saito, Norihiro Miura, Maki Miyajima, Sena Yamamoto, Tsukasa Sato, Takatoshi Yotsuyanagi, Mineko Fujimiya, Takako S Chikenji

  Communications biology   5 ( 1 ) 310 - 310  2022.04  [Refereed]  [International journal]

  Authorship：   Corresponding author

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  Pathologic diabetic wound healing is caused by sequential and progressive deterioration of hemostasis, inflammation, proliferation, and resolution/remodeling. Cellular senescence promotes wound healing; however, diabetic wounds exhibit low levels of senescent factors and accumulate senescent cells, which impair the healing process. Here we show that the number of p15INK4B + PDGFRα + senescent mesenchymal cells in adipose tissue increases transiently during early phases of wound healing in both non-diabetic mice and humans. Transplantation of adipose tissue from diabetic mice into non-diabetic mice results in impaired wound healing and an altered cellular senescence-associated secretory phenotype (SASP), suggesting that insufficient induction of adipose tissue senescence after injury is a pathological mechanism of diabetic wound healing. These results provide insight into how regulation of senescence in adipose tissue contributes to wound healing and could constitute a basis for developing therapeutic treatment for wound healing impairment in diabetes.

  DOI PubMed

• Fisetin reduces the senescent tubular epithelial cell burden and also inhibits proliferative fibroblasts in murine lupus nephritis.

  Shogo Ijima, Yuki Saito, Kentaro Nagaoka, Sena Yamamoto, Tsukasa Sato, Norihiro Miura, Taiki Iwamoto, Maki Miyajima, Takako S Chikenji

  Frontiers in immunology   13   960601 - 960601  2022  [Refereed]  [International journal]

  Authorship：   Corresponding author

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  Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease characterized by the involvement of multiple organs. Lupus nephritis (LN) is a major risk factor for overall morbidity and mortality in SLE patients. Hence, designing effective drugs is pivotal for treating individuals with LN. Fisetin plays a senolytic role by specifically eliminating senescent cells, inhibiting cell proliferation, and exerting anti-inflammatory, anti-oxidant, and anti-tumorigenic effects. However, limited research has been conducted on the utility and therapeutic mechanisms of fisetin in chronic inflammation. Similarly, whether the effects of fisetin depend on cell type remains unclear. In this study, we found that LN-prone MRL/lpr mice demonstrated accumulation of Ki-67-positive myofibroblasts and p15INK4B-positive senescent tubular epithelial cells (TECs) that highly expressed transforming growth factor β (TGF-β). TGF-β stimulation induced senescence of NRK-52E renal TECs and proliferation of NRK-49F renal fibroblasts, suggesting that TGF-β promotes senescence and proliferation in a cell type-dependent manner, which is inhibited by fisetin treatment in vitro. Furthermore, fisetin treatment in vivo reduced the number of senescent TECs and myofibroblasts, which attenuated kidney fibrosis, reduced senescence-associated secretory phenotype (SASP) expression, and increased TEC proliferation. These data suggest that the effects of fisetin vary depending on the cell type and may have therapeutic effects in complex and diverse LN pathologies.

  DOI PubMed

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• 【老化を標的とした疾患予防・治療】老化細胞の光と影

  千見寺 貴子, 齋藤 悠城

  医学のあゆみ ( 医歯薬出版(株) )  287 ( 5 ) 321 - 326  2023.11

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  細胞老化はさまざまな臓器における慢性炎症や線維化,さらには個体老化との関連性が報告されたことから,健康寿命を延伸する治療ターゲットとして注目されている.一方で,細胞老化はがん抑制機構として知られるだけでなく,胚の発生,創傷治癒さらには組織幹細胞の活性化を介した組織再生や,リプログラミングに至るまで幅広い生物学的プロセスに関与する,生体にとって有益な役割も担っていることが明らかになっている.そのため,"光"と"影"を含めた細胞老化の多面的な理解が,安全で有効な老化細胞をターゲットとした疾病予防・治療の確立に向けて重要な課題と考えられている.本稿では,細胞老化の多様な役割のなかで,特に細胞老化の有益な働きを中心に,さまざまな枠組みにおける細胞老化の役割について紹介する.(著者抄録)

• 骨格筋における細胞老化と筋再生

  千見寺 貴子, 齋藤 悠城

  基礎老化研究 ( 日本基礎老化学会 )  46 ( 3 ) 8 - 8  2022.10

• 骨格筋の再生と細胞老化

  齋藤 悠城, 千見寺 貴子

  基礎理学療法学 ( (一社)日本基礎理学療法学会 )  25 ( 1 ) 61 - 68  2022.10

  　View Summary

  細胞老化はがん抑制や個体発生,さらには組織再生など生体に重要な機能を果たす一方で,加齢や慢性炎症などを進展する二面性が報告されている。近年,骨格筋への運動ストレスが細胞老化を誘導して骨格筋の修復や再生を促進するだけでなく,慢性炎症や線維化など骨格筋病態へも関与することが明らかになってきた。細胞老化制御機構の解明は新たな骨格筋治療の突破口になる可能性を秘めている。本稿では,運動による骨格筋の細胞老化と組織修復プロセスを中心に,骨格筋における細胞老化の影響について概説する。(著者抄録)

• 運動による細胞老化制御と骨格筋再生

  Yuki Saito, Takako S. Chikenji

  実験医学   40 ( 2 ) 86 - 91  2021.01  [Invited]

  Authorship：   Lead author

• 【手根管症候群の治療トピックス】手根管症候群の病態と結合組織の線維化

  射場 浩介, 齋藤 悠城, 千見寺 貴子, 山下 敏彦

  Orthopaedics ( (株)全日本病院出版会 )  33 ( 4 ) 7 - 12  2020.04

  　View Summary

  手根管症候群の主な病態として、手根管内圧の上昇が考えられている。内圧が上昇する原因として、手根管周囲結合組織の肥厚や線維化が報告されている。結合組織線維化の発生機序の一つに滑膜下結合組織(subsynovial connective tissue:SSCT)の線維化が注目されている。SSCT線維化の発症機序として、トランスフォーミング増殖因子ベータ(TGFβ)の発現増強や血小板成長因子受容体(PDGFR)の活性化が関与していることがこれまでの研究で明らかとなってきた。また、これらの下流因子に対する阻害薬は、SSCT由来細胞の増殖および線維化関連遺伝子の発現を調節する効果を有していた。このことは、TGFβやPDGFRに対する調節因子がSSCTの線維化を抑制することで、手根管症候群の発症や病態の進行を予防するとともに、症状の改善効果を有する可能性を示唆している。手根管症候群の病態におけるSSCT線維化について、今後のさらなる研究成果が新しい治療法の開発につながることに期待する。(著者抄録)

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Other 【 display / non-display 】

Other 【 display / non-display 】

• 死体解剖資格(系統解剖)

  2022

  　

  　

Awards 【 display / non-display 】

Awards 【 display / non-display 】

• Top-scoring abstracts

  2023.12   Cell Bio 2023, the joint meeting of the American Society for Cell Biology (ASCB) and European Molecular Biology Organization (EMBO)  

• Best Poster Award

  2023.07   日本炎症・再生医学会  

  Winner： Yuki Saito, Takako S. Chikenji

• 札幌医科大学大学院医学研究科 若手研究者最優秀論文賞

  2021.01   Sapporo Medical University  

• New Investigator Recognition Award (NIRA)

  2020.02   Orthopedic Research Society   Exercise enhances skeletal muscle regeneration by promoting senescence in fibro-adipogenic progenitors

  Winner： Yuki Saito, Takako S. Chikenji, Takashi Matsumura, Mineko Fujimiya

Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• 健康長寿社会の創成に向けた運動記憶細胞の解明

  Project Year :

  2024.10

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  2028.03

   

  Authorship： Principal investigator

• 老化細胞が形成する細胞間ネットワークに着眼した関節リウマチ病態の解明

  Project Year :

  2024.07

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  2027.03

   

  Authorship： Coinvestigator(s)

• 老化細胞の運命決定機構から解明する関節リウマチ病態メカニズムと関節再生戦略

  基盤研究(B)

  Project Year :

  2024.04

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  2027.03

   

  千見寺 貴子, 齋藤悠城

• 運動誘発性細胞老化を基軸とした臓器間コミュニケーションと組織適応・修復機構の解明

  基盤研究(B)

  Project Year :

  2024.04

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  2027.03

   

  齋藤 悠城

• 老化起源細胞から解明するHealthy agingと加齢性疾患の分岐点

  挑戦的研究(萌芽)

  Project Year :

  2023.06

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  2026.03

   

  齋藤 貴子, 齋藤 悠城

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Presentations 【 display / non-display 】

Presentations 【 display / non-display 】

• Cellular Senescence in Tendon Aging and Pathology

  Yuki Saito, Takako S. Chikenji, Alyssa Vrieze, Tamara Tchkonia, James L. Kirkland, Peter C. Amadio, Anne Gingery

  Orthopedic Research Society Spotlight Session 

  Presentation date： 2020.02

  Event date：

  2020.02

  　

  　

• Exercise enhances skeletal muscle regeneration by promoting senescence in fibro-adipogenic progenitors

  Yuki Saito, Takashi Matsumura, Mineko Fujimiya, Takako S. Chikenji

  Orthopedic Research Society 

  Presentation date： 2020.02

  Event date：

  2020.02

  　

  　

• 骨格筋間葉系前駆細胞の細胞老化と骨格筋の再生

  齋藤悠城, 千見寺貴子

  第26回日本基礎理学療法学会学術集会 シンポジウム２：U-39最先端研究紹介 

  Presentation date： 2021.10

• Fisetin improved depressive behavior in murine lupus by decreasing senescent neural cell.

  Yuki Saito, Maki Miyajima, Sena Yamamoto, Tsukasa Sato, Norihiro Miura, Mineko Fujimiya, Takako S. Chikenji

  The 6th International Cell Senescence Association Conference 

  Presentation date： 2021.12

• Exercise-induced senescence-like gene signature in fibro/adipogenic progenitors is impaired in diabetes muscle,

  Yuki Saito, Norihiro Miura, Sena Yamamoto, Tsukasa Sato, Kentaro Nagaoka, Taiki Iwamoto, Maki Miyajima, Arisa Kita, Takako S. Chikenji

  ASCB|EMBO meeting Cell Bio 2023, , Minisymposia 

  Presentation date： 2023.12

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