組織が成長するとき、細胞はどのように環境に影響されるのか(How cells are influenced by their environment as tissues grow)

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2023-05-03 スイス連邦工科大学チューリッヒ校(ETHZurich)

◆ETHのViola Vogel教授とMario C. Benn上級助手は、新しい組織培養システムを用いて、細胞と体細胞を包む繊維状の構造体である細胞外マトリックス(ECM)の相互作用を試験管内で研究しました。
◆組織の成長を再現することで、細胞とECMの相互作用が組織の成長を制御する上で重要であることを示し、ヒト皮下組織における創傷治癒の後期段階で起こるプロセスを発見した。
◆この研究は、線維症や癌の新しい治療法の開発や、動物実験の回避に貢献する可能性があります。

<関連情報>

メカノバイオロジーは、微小組織の成長を促進するECMと細胞の相互作用の反復をどのように制御しているのか? How the mechanobiologyorchestrates the iterative andreciprocalECM-cellcross-talkthat drivesmicrotissuegrowth

Mario C. Benn,Simon A. Pot,Jens Moeller,Tadahiro Yamashita,Charlotte M. Fonta,Gertraud Orend,Philip Kollmannsberger,Viola Vogel
Science Advances  Published:29 Mar 2023
DOI:https://doi.org/10.1126/sciadv.add9275

Abstract

Controlled tissue growth is essential for multicellular life and requires tight spatiotemporal control over cell proliferation and differentiation until reaching homeostasis. As cells synthesize and remodel extracellular matrix, tissue growth processes can only be understood if the reciprocal feedback between cells and their environment is revealed. Using de novo–grown microtissues, we identified crucial actors of the mechanoregulated events, which iteratively orchestrate a sharp transition from tissue growth to maturation, requiring a myofibroblast-to-fibroblast transition. Cellular decision-making occurs when fibronectin fiber tension switches from highly stretched to relaxed, and it requires the transiently up-regulated appearance of tenascin-C and tissue transglutaminase, matrix metalloprotease activity, as well as a switch from α5β1 to α2β1 integrin engagement and epidermal growth factor receptor signaling. As myofibroblasts are associated with wound healing and inflammatory or fibrotic diseases, crucial knowledge needed to advance regenerative strategies or to counter fibrosis and cancer progression has been gained.

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