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dc.contributor.authorGalli, Alessandra
dc.contributor.authorMaffioli, Elisa
dc.contributor.authorSogne, Elisa
dc.contributor.authorMoretti, Stefania
dc.contributor.authorDi Cairano, Eliana Sara
dc.contributor.authorNegri, Armando
dc.contributor.authorNonnis, Simona
dc.contributor.authorNorata, Giuseppe Danilo
dc.contributor.authorBonacina, Fabrizia
dc.contributor.authorBorghi, Francesca
dc.contributor.authorPodestà, Alessandro
dc.contributor.authorBertuzzi, Federico
dc.contributor.authorMilani, Paolo
dc.contributor.authorLenardi, Cristina
dc.contributor.authorTedeschi, Gabriella
dc.contributor.authorPerego, Carla
dc.date.accessioned2018-09-03T13:20:49Z
dc.date.available2018-09-03T13:20:49Z
dc.date.issued2018-07-02
dc.identifier.citationGalli A, Maffioli E, Sogne E, Moretti S, Di Cairano ES, et al. (2018) Cluster-assembled zirconia substrates promote long-term differentiation and functioning of human islets of Langerhans. Scientific Reports 8. Available: http://dx.doi.org/10.1038/s41598-018-28019-3.
dc.identifier.issn2045-2322
dc.identifier.doi10.1038/s41598-018-28019-3
dc.identifier.urihttp://hdl.handle.net/10754/628397
dc.description.abstractEx vivo expansion and differentiation of human pancreatic β-cell are enabling steps of paramount importance for accelerating the development of therapies for diabetes. The success of regenerative strategies depends on their ability to reproduce the chemical and biophysical properties of the microenvironment in which β-cells develop, proliferate and function. In this paper we focus on the biophysical properties of the extracellular environment and exploit the cluster-assembled zirconia substrates with tailored roughness to mimic the nanotopography of the extracellular matrix. We demonstrate that β-cells can perceive nanoscale features of the substrate and can convert these stimuli into mechanotransductive processes which promote long-term in vitro human islet culture, thus preserving β-cell differentiation and function. Proteomic and quantitative immunofluorescence analyses demonstrate that the process is driven by nanoscale topography, via remodelling of the actin cytoskeleton and nuclear architecture. These modifications activate a transcriptional program which stimulates an adaptive metabolic glucose response. Engineered cluster-assembled substrates coupled with proteomic approaches may provide a useful strategy for identifying novel molecular targets for treating diabetes mellitus and for enhancing tissue engineering in order to improve the efficacy of islet cell transplantation therapies.
dc.description.sponsorshipWe would like to thank Giulia Crosta for his assistance in data collection, Carsten Schulte for drawing Figure 7 and for valuable discussions, Eleanor Lea for manuscript editing. This work was supported by Università degli Studi di Milano (Piano di Sostegno per la Ricerca, Università degli Studi di Milano, 2015–2017 Linea2 - Azione A) (to C.P.). E.S.D.C. was the recipient of Postdoctoral fellowships from the Università degli Studi di Milano. This work was also supported by the “National Funding for Basic Research” (FIRB) as part of a project entitled “Oxides at the Nanoscale: Functionalities and Applications” (FIRB RBAP11AYN) and by the European Union project “FutureNanoNeeds” grant “Framework to respond to regulatory needs of future nanomaterials and markets” (FP7-NMP-2013-LARGE-7).
dc.publisherSpringer Nature
dc.relation.urlhttp://link.springer.com/article/10.1038/s41598-018-28019-3
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleCluster-assembled zirconia substrates promote long-term differentiation and functioning of human islets of Langerhans
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.identifier.journalScientific Reports
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionDipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, via Trentacoste 2, Milan, 20134, , Italy
dc.contributor.institutionFondazione Filarete, v.le Ortles 22/4, Milan, 20139, , Italy
dc.contributor.institutionDipartimento di Medicina Veterinaria, Università degli Studi di Milano Italy, via Celoria 10, Milan, 20133, , Italy
dc.contributor.institutionCIMAINA, Dipartimento di Fisica, Università degli Studi di Milano, via Celoria 16, Milan, 20133, , Italy
dc.contributor.institutionNiguarda Hospital, Milan, , Italy
kaust.personSogne, Elisa
refterms.dateFOA2018-09-11T08:00:12Z
dc.date.published-online2018-07-02
dc.date.published-print2018-12


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This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's license is described as This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.