マウスにおけるグルコース感知インスリン分泌ヒトα細胞による糖尿病緩和
Kenichiro Furuyama1, Simona Chera1,2, Léon van Gurp1
1Department of Genetic Medicine and Development, iGE3 and Centre Facultaire du Diabète, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Nature
|February 15, 2019
まとめ
ヒトの小島細胞は インスリンを産生する細胞に 変容し 糖尿病の新たな治療法となる可能性があります 人間の臓の 細胞の可塑性は 再生医療に希望を与えてくれます
科学分野:
- 内分泌学
- 再生医療
- 細胞生物学
背景:
- 細胞アイデンティティスイッチは動物では知られている再生戦略ですが,哺乳類では十分に理解されていません.
- マウスでは,臓のアルファ細胞とデルタ細胞は,ベータ細胞の喪失後,インスリン産生ベータ細胞に変換することができる.
- ヒトの小島細胞の可塑性は,特に糖尿病では,ほとんど知られていない.
研究 の 目的:
- ヒトの小島型非ベータ細胞 (アルファ細胞とガンマ細胞) が可塑性を示すかどうかを調査する.
- ヒトの細胞がインスリンを 生み出すように 再プログラムできるかどうか
- 糖尿病治療におけるヒトの小島細胞の治療の可能性を評価する.
主な方法:
- 非糖尿病患者と糖尿病のドナーのヒト小島細胞の系統が追跡されました.
- 非ベータ細胞 (アルファとPPYを生成するガンマ細胞) は,転写因子PDX1とMAFAを使用して再プログラムされた.
- 変換した細胞を糖尿病のマウスに移植し,インスリン生成と糖尿病の逆転を評価した.
- 変換されたインスリン産生アルファ細胞に深部トランスクリプトミクスとプロテオミクス分析が行われました.
主要な成果:
- ヒトの小島アルファ細胞とガンマ細胞は,グルコースに反応してインスリンを産生し分泌するように再プログラムされ,成功しました.
- 移植されたヒトアルファ細胞はマウスの糖尿病を逆転させ,少なくとも6ヶ月間インスリン生成を維持した.
- 再プログラムされたアルファ細胞はアルファ細胞マーカーの発現を維持し,安定した細胞同一性を示した.
- 深層分子特徴は 変換された細胞の可塑性と機能を確認した.
結論:
- ヒトの小島細胞は可塑性を持ち,非ベータ細胞を機能的なインスリン生成細胞に変換することができる.
- この細胞の再プログラミングは 再生医療による 糖尿病治療の有望な道を示しています
- この発見は,糖尿病やその他の退廃性疾患の治療のために細胞の可塑性を理解し,利用するための分子枠組みを提供します.
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