Details of a Researcher - Shinmura, Shigeto

Shinmura, Shigeto

写真a

Affiliation: School of Medicine, Department of Ophthalmology （Shinanomachi）

Position: Associate Professor

Related Websites

http://shimmura.net/top/

External Links

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Academic Background 【 Display / hide 】

1989.03

Keio University, 医学部

Graduated

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Research Areas 【 Display / hide 】

Ophthalmology

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Papers 【 Display / hide 】

Senescence-associated secretory phenotype promotes chronic ocular graft-vs-host disease in mice and humans

Yamane M., Sato S., Shimizu E., Shibata S., Hayano M., Yaguchi T., Kamijuku H., Ogawa M., Suzuki T., Mukai S., Shimmura S., Okano H., Takeuchi T., Kawakami Y., Ogawa Y., Tsubota K.

FASEB Journal （FASEB Journal) 2020

ISSN 08926638

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© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology Chronic graft-vs-host disease (cGVHD) is a multifactorial inflammatory disease that affects patients undergoing hematopoietic stem cell transplantation. Multiple organs, including the lacrimal glands (LGs), are negatively affected by cGVHD and lose function due to the resultant fibrosis. An abnormal immune response is thought to be a major factor in the development of chronic ocular GVHD, which is currently treated primarily with immunosuppressive therapies. However, all the treatments yield unsatisfactory outcomes, and additional treatment strategies are needed. To meet this unmet medical need, we aimed to elucidate an additional pathway of chronic ocular GVHD. Our findings suggest a potential association between chronic ocular GVHD pathogenesis and stress-induced cellular senescence through the senescence-associated secretory phenotype (SASP). Senescent cells produce cytokines and chemokines, such as IL-6 and CXCL9. Indeed, senescent cell accumulation was presumably associated with cGVHD development in LGs, as evidenced by the improvement in LGs after the selective elimination of senescent cells (senolysis) with ABT-263. Results in the sclerodermatous cGVHD mouse model suggest that inhibiting the major components of the SASP, including IL-6 and CXCL9, with senolytics is a potential novel strategy for treating cGVHD-affected LGs. Taken together, our results indicate a potential association between the SASP and cGVHD development in LGs and suggest that targeted senolytic treatment may be a new therapeutic option for this disease.
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Review: Corneal endothelial cell derivation methods from ES/iPS cells

Hatou S., Shimmura S.

Inflammation and Regeneration （Inflammation and Regeneration) 39 （ 1 ） 2019.10

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© 2019 The Author(s). Globally, approximately 12.7 million people are awaiting a transplantation, while only 185,000 cases of corneal transplantation are performed in a year. Corneal endothelial dysfunction (bullous keratopathy) due to Fuchs' corneal endothelial dystrophy, or insults associated with intraocular surgeries, shared half of all indications for corneal transplantation. Regenerative therapy for corneal endothelium independent of eye bank eyes has great importance to solve the large supply-demand mismatching in corneal transplantation and reduce the number of worldwide corneal blindness. If corneal endothelial cells could be derived from ES or iPS cells, these stem cells would be the ideal cell source for cell therapy treatment of bullous keratopathy. Four representative corneal endothelial cell derivation methods were reviewed. Components in earlier methods included lens epithelial cell-conditioned medium or fetal bovine serum, but the methods have been improved and materials have been chemically more defined over the years. Conditioned medium or serum is replaced to recombinant proteins and small molecule compounds. These improvements enabled to open the corneal endothelial developmental mechanisms, in which epithelial-mesenchymal and mesenchymal-endothelial transition by TGF beta, BMP, and Wnt signaling have important roles. The protocols are gradually approaching clinical application; however, proof of efficacy and safety of the cells by adequate animal models are the challenges for the future.
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Global consensus on definition, classification, diagnosis, and staging of limbal stem cell deficiency

Deng S., Borderie V., Chan C., Dana R., Figueiredo F., Gomes J., Pellegrini G., Shimmura S., Kruse F.

Cornea （Cornea) 38 （ 3 ） 364 - 375 2019.03

ISSN 02773740

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© 2018 Wolters Kluwer Health, Inc. All rights reserved. Purpose: Despite extensive knowledge gained over the last 3 decades regarding limbal stem cell deficiency (LSCD), the disease is not clearly defined, and there is lack of agreement on the diagnostic criteria, staging, and classification system among treating physicians and research scientists working on this field. There is therefore an unmet need to obtain global consensus on the definition, classification, diagnosis, and staging of LSCD. Methods: A Limbal Stem Cell Working Group was first established by The Cornea Society in 2012. The Working Group was divided into subcommittees. Four face-to-face meetings, frequent email discussions, and teleconferences were conducted since then to obtain agreement on a strategic plan and methodology from all participants after a comprehensive literature search, and final agreement was reached on the definition, classification, diagnosis, and staging of LSCD. A writing group was formed to draft the current manuscript, which has been extensively revised to reflect the consensus of the Working Group. Results: A consensus was reached on the definition, classification, diagnosis, and staging of LSCD. The clinical presentation and diagnostic criteria of LSCD were clarified, and a staging system of LSCD based on clinical presentation was established. Conclusions: This global consensus provides a comprehensive framework for the definition, classification, diagnosis, and staging of LSCD. The newly established criteria will aid in the correct diagnosis and formulation of an appropriate treatment for different stages of LSCD, which will facilitate a better understanding of the condition and help with clinical management, research, and clinical trials in this area.
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Prognosis after lamellar keratoplasty for limbal dermoids using preserved corneas

Yamashita K., Hatou S., Uchino Y., Tsubota K., Shimmura S.

Japanese Journal of Ophthalmology （Japanese Journal of Ophthalmology) 63 （ 1 ） 56 - 64 2019.01

ISSN 00215155

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© 2018, Japanese Ophthalmological Society. Purpose: To evaluate the safety and efficacy of lamellar keratoplasty using preserved donor corneas to treat limbal dermoids. Study design: Retrospective study. Methods: The clinical records of 19 patients with limbal dermoids, who underwent lamellar keratoplasty using preserved corneas that were observed for more than 6 months at the Keio University School of Medicine between January, 2000 and December, 2017, were retrospectively reviewed. We retrospectively analyzed demographics, surgical outcomes, the occurrence of any surgically induced changes in refraction, and intra and postoperative complications. Results: Patient age at surgery showed 2 peaks, the first ranged from 0 to 6 years, and the second from 13 to 20 years. All patients except one had good cosmetic results. Preoperative astigmatism was more than 2 diopters in 12 of 16 eyes for which refractive data were recorded. The refractive cylinder in 8 of the 16 eyes differed after surgery by less than 2 diopters. Treatment of amblyopia by occlusion of the fellow eye and spectacle prescription was done either prior to or following surgery, and resulted in improved visual acuity in 7 patients. Intraoperative complications did not occur in any of the patients. Postoperatively, all patients except one showed corneal re-epithelialization within a week. Conclusion: Lamellar keratoplasty using preserved corneas for limbal dermoid yields good cosmetic results. However, improvements in astigmatism and visual acuity are not guaranteed. Preoperative treatment of amblyopia gives a better prognosis for improved visual acuity postoperatively. Long-term observation including amblyopia treatment is required before and after surgery.
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Immunological Properties of Neural Crest Cells Derived from Human Induced Pluripotent Stem Cells

Fujii S., Yoshida S., Inagaki E., Hatou S., Tsubota K., Takahashi M., Shimmura S., Sugita S.

Stem Cells and Development （Stem Cells and Development) 28 （ 1 ） 28 - 43 2019.01

ISSN 15473287

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© Shota Fujii et al. 2018; Published by Mary Ann Liebert, Inc. 2018. Collecting sufficient quantities of primary neural crest cells (NCCs) for experiments is difficult, as NCCs are embryonic transient tissue that basically does not proliferate. We successfully induced NCCs from human induced pluripotent stem cells (iPSCs) in accordance with a previously described method with some modifications. The protocol used in this study efficiently produced large amounts of iPSC-derived NCCs (iPSC-NCCs). Many researchers have recently produced large amounts of iPSC-NCCs and used these to examine the physiological properties, such as migratory activity, and the potential for medical uses such as wound healing. Immunological properties of NCCs are yet to be reported. Therefore, the purpose of this study was to assess the immunological properties of human iPSC-NCCs. Our current study showed that iPSC-NCCs were hypoimmunogenic and had immunosuppressive properties in vitro. Expression of HLA class I molecules on iPSC-NCCs was lower than that observed for iPSCs, and there was no expression of HLA class II and costimulatory molecules on the cells. With regard to the immunosuppressive properties, iPSC-NCCs greatly inhibited T cell activation (cell proliferation and production of inflammatory cytokines) after stimulation. iPSC-NCCs constitutively expressed membrane-bound TGF-β, and TGF-β produced by iPSC-NCCs played a critical role in T cell suppression. Thus, cultured human NCCs can fully suppress T cell activation in vitro. This study may contribute to the realization of using stem cell-derived NCCs in cell-based medicine.
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Papers, etc., Registered in KOARA 【 Display / hide 】

Elucidating the pathogenesis of Fuchs corneal dystrophy using disease iPSCs

Shinmura, Shigeto

科学研究費補助金研究成果報告書 2018
Immunological properties of corneal endothelial cells derived from human induced pluripotent stem cells

Shinmura, Shigeto

科学研究費補助金研究成果報告書 2017
Label retaining cells in long term cultured confluent epithelial cell sheets

Shinmura, Shigeto

科学研究費補助金研究成果報告書 2016
A significant role of senescent cells and donor mesenchymal stem cells in ocular chronic graft-versus-host disease and development of new therapy

Shinmura, Shigeto

科学研究費補助金研究成果報告書 2016
Melanocyte stem cells as a niche for corneal epithelial stem cells

Shinmura, Shigeto

科学研究費補助金研究成果報告書 2014

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Reviews, Commentaries, etc. 【 Display / hide 】

Reply

Deng S.X., Borderie V., Chan C.C., Dana R., Figueiredo F.C., Gomes J.A.P., Pellegrini G., Shimmura S., Kruse F.E.

Cornea (Cornea) 38 ( 12 ) E56 - E57 2019.12

ISSN 02773740
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Research Projects of Competitive Funds, etc. 【 Display / hide 】

ドラッグ・リポジショニングによるフックス角膜変性症治療薬の開発

2019.04

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2022.03

MEXT,JSPS, Grant-in-Aid for Scientific Research, 榛村　重人, Grant-in-Aid for Scientific Research (C), Principal Investigator
フックス角膜内皮変性症の疾患特異的iPS細胞による病態解明

2016.04

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2019.03

MEXT,JSPS, Grant-in-Aid for Scientific Research, 榛村　重人, Grant-in-Aid for Scientific Research (C), Principal Investigator