2022 Fiscal Year Final Research Report
Regenerative medicine research on osteo-related tissues using Ehlers–Danlos syndrome spondylodysplastic type 3 induced pluripotent stem cells
| Project/Area Number |
20K07457
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | Tokushima Bunri University |
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Principal Investigator |
Shoji Masaki 徳島文理大学, 薬学部, 講師 (00636821)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 脊椎手掌異形成型エーラス・ダンロス症候群 / 疾患特異的iPS細胞 / CRISPR/Cas9 / 一塩基修復細胞 / 分化誘導 / 間葉系間質細胞 / 骨芽細胞 |
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| Outline of Final Research Achievements |
ZIP13 dysfunction caused by the homozygosity for a GGT to GAT transition changing codon 64 from Gly(G) to Asp(D) in its gene (ZIP13-G64D) is responsible for Ehlers-Danlos syndrome spondylodysplastic type 3 (EDSSPD3). However, the development research on therapeutic agents against EDSSPD3-patients have not been reported. In this study, we were generated from dermal fibroblasts of EDSSPD3-patients to induced pluripotent stem cells (iPSCs). We repaired a G64D point mutated ZIP13 gene in EDSSPD3-patients iPSCs using CRISPR/Cas9 system. Next, EDSSPD3-patients iPSCs were differentiated to mesenchymal stem cells (MSCs) via neural crest cells. Osteoblast differentiated from MSCs of EDSSPD3-iPSCs was low osteogenic potential as comparison with those of MSCs of healthy control and ZIP13-G64D repaired clones. These results suggested that ZIP13-G64D mutation in EDSSPD3-patient iPSCs was attenuated in a differentiation potency from MSCs to osteoblasts.
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| Free Research Field |
医歯薬学・医学・ウイルス学関連および実験病理学関連
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、当該患者iPS細胞のZIP13-G64D点変異修復株由来MSCを用いて、点変異を起因としたMSCの骨形成能低下を示唆する結果を得た。これらは、EDSSPD3患者における骨・軟骨細胞の分化と機能にかかわるシグナル経路を解析でき、治療薬の新しい標的を発見できる。さらに、患者iPS細胞由来MSCを用いて実施される薬剤スクリーニングは、患者由来の細胞を用いる点で、直接的な治療薬の発見に繋がる。そして、EDSSPD3患者のZIP13-G64D点変異修復iPS細胞株は、当該患者の正常な骨・軟骨細胞を作製でき、患者本人に拒絶反応なく移植できることから、再生医療への発展性も秘めている。
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