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

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...

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Autores principales: Alessandra, Galli, Algerta, Marku, Paola, Marciani, Carsten, Schulte, Cristina, Lenardi, Paolo, Milani, Elisa, Maffioli, Gabriella, Tedeschi, Carla, Perego
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072458/
https://www.ncbi.nlm.nih.gov/pubmed/32053947
http://dx.doi.org/10.3390/cells9020413
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author Alessandra, Galli
Algerta, Marku
Paola, Marciani
Carsten, Schulte
Cristina, Lenardi
Paolo, Milani
Elisa, Maffioli
Gabriella, Tedeschi
Carla, Perego
author_facet Alessandra, Galli
Algerta, Marku
Paola, Marciani
Carsten, Schulte
Cristina, Lenardi
Paolo, Milani
Elisa, Maffioli
Gabriella, Tedeschi
Carla, Perego
author_sort Alessandra, Galli
collection PubMed
description 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.
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spelling pubmed-70724582020-03-19 Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction Alessandra, Galli Algerta, Marku Paola, Marciani Carsten, Schulte Cristina, Lenardi Paolo, Milani Elisa, Maffioli Gabriella, Tedeschi Carla, Perego Cells Review 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. MDPI 2020-02-11 /pmc/articles/PMC7072458/ /pubmed/32053947 http://dx.doi.org/10.3390/cells9020413 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Alessandra, Galli
Algerta, Marku
Paola, Marciani
Carsten, Schulte
Cristina, Lenardi
Paolo, Milani
Elisa, Maffioli
Gabriella, Tedeschi
Carla, Perego
Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction
title Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction
title_full Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction
title_fullStr Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction
title_full_unstemmed Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction
title_short Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction
title_sort shaping pancreatic β-cell differentiation and functioning: the influence of mechanotransduction
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072458/
https://www.ncbi.nlm.nih.gov/pubmed/32053947
http://dx.doi.org/10.3390/cells9020413
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