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オカノ テルオ
Okano Teruo
岡野 光夫 所属 医学研究科 医学研究科 (医学部医学科をご参照ください) 職種 評議員 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Improvement of the therapeutic capacity of insulin-producing cells trans-differentiated from human liver cells using engineered cell sheet. |
| 掲載誌名 | 正式名：Stem cell research & therapy 略 称：Stem Cell Res Ther ISSNコード：17576512/17576512 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 12(1),pp.3 |
| 著者・共著者 | Lee Yu Na†, Yi Hye-Jin, Seo Eun Hye, Oh Jooyun, Lee Song, Ferber Sarah, Okano Teruo, Shim In Kyong*, Kim Song Cheol* |
| 発行年月 | 2021/01/06 |
| 概要 | BACKGROUND:Although pancreatic islet transplantation therapy is ideal for diabetes patients, several hurdles have prevented it from becoming a standard treatment, including donor shortage and low engraftment efficacy. In this study, we prepared insulin-producing cells trans-differentiated from adult human liver cells as a new islet source. Also, cell sheet formation could improve differentiation efficiency and graft survival.
METHODS:Liver cells were expanded in vitro and trans-differentiated to IPCs using adenovirus vectors carrying human genes for PDX1, NEUROD1, and MAFA. IPCs were seeded on temperature-responsive culture dishes to form cell sheets. Differentiation efficiency was confirmed by ß cell-specific gene expression, insulin production, and immunohistochemistry. IPC suspension was injected by portal vein (PV), and IPC sheet was transplanted on the liver surface of the diabetic nude mouse. The therapeutic effect of IPC sheet was evaluated by comparing blood glucose control, weight gain, histological evaluation, and hepatotoxicity with IPC injection group. Also, cell biodistribution was assessed by in vivo/ex vivo fluorescence image tagging.RESULTS:Insulin gene expression and protein production were significantly increased on IPC sheets compared with those in IPCs cultured on conventional culture dishes. Transplanted IPC sheets displayed significantly higher engraftment efficiency and fewer transplanted cells in other organs than injected IPCs, and also lower liver toxicity, improved blood glucose levels, and weight gain. Immunohistochemical analyses of liver tissue revealed positive staining for PDX1 and insulin at 1, 2, and 4 weeks after IPC transplantation. |
| DOI | 10.1186/s13287-020-02080-0 |
| PMID | 33407888 |