Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction

Cells

Schulte Carsten¹  Lenardi Cristina¹  Milani Paolo¹  Perego Carla²  Marku Algerta²  Galli Alessandra²  Marciani Paola²  Maffioli Elisa³  Tedeschi Gabriella³ 

[1] CIMAINA, Department of Physics, Università degli Studi di Milano, 20133 Milan, Italy;Department of Excellence of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20134 Milan, Italy;Department of Veterinary Medicine, Università degli Studi di Milano, 20133 Milan, Italy;

关键词: β-cells;    mechanotransduction;    diabetes;    stem cells;    nanotopography;    islet of langerhans;    integrin;    yap/taz;    actin;   

DOI  :  10.3390/cells9020413

来源: DOAJ

【 摘 要 】

Embryonic and pluripotent stem cells hold great promise in generating β-cells for both replacing medicine and novel therapeutic discoveries in diabetes mellitus. However, their differentiation in vitro is still inefficient, and functional studies reveal that most of these β-like cells still fail to fully mirror the adult β-cell physiology. For their proper growth and functioning, β-cells require a very specific environment, the islet niche, which provides a myriad of chemical and physical signals. While the nature and effects of chemical stimuli have been widely characterized, less is known about the mechanical signals. We here review the current status of knowledge of biophysical cues provided by the niche where β-cells normally live and differentiate, and we underline the possible machinery designated for mechanotransduction in β-cells. Although the regulatory mechanisms remain poorly understood, the analysis reveals that β-cells are equipped with all mechanosensors and signaling proteins actively involved in mechanotransduction in other cell types, and they respond to mechanical cues by changing their behavior. By engineering microenvironments mirroring the biophysical niche properties it is possible to elucidate the β-cell mechanotransductive-regulatory mechanisms and to harness them for the promotion of β-cell differentiation capacity in vitro.

【 授权许可】

Unknown