Department of Excellence of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20134 Milan, Italy.
CIMAINA, Department of Physics, Università degli Studi di Milano, 20133 Milan, Italy.
Cells. 2020 Feb 11;9(2):413. doi: 10.3390/cells9020413.
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.
胚胎干细胞和多能干细胞在产生β细胞方面具有很大的潜力，既可以用于替代医学，也可以用于糖尿病的新型治疗发现。然而，它们在体外的分化仍然效率低下，功能研究表明，大多数这些β样细胞仍然不能完全反映成年β细胞的生理学。为了正常生长和发挥功能，β细胞需要一个非常特殊的环境，即胰岛微环境，它提供了无数的化学和物理信号。虽然化学刺激的性质和作用已经得到了广泛的描述，但关于力学信号的了解较少。在这里，我们回顾了β细胞正常生活和分化的微环境所提供的生物物理线索的最新知识，并强调了β细胞中机械转导可能指定的机制。尽管调控机制仍知之甚少，但分析表明，β细胞配备了所有的机械感受器和信号蛋白，积极参与其他细胞类型中的机械转导，并且它们通过改变行为来响应机械线索。通过构建模拟生物物理微环境的特性，可以阐明β细胞的机械转导调控机制，并利用它们来促进体外β细胞的分化能力。
