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      Overview of Micro- and Nano-Technology Tools for Stem Cell Applications: Micropatterned and Microelectronic Devices

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          Abstract

          In the past few decades the scientific community has been recognizing the paramount role of the cell microenvironment in determining cell behavior. In parallel, the study of human stem cells for their potential therapeutic applications has been progressing constantly. The use of advanced technologies, enabling one to mimic the in vivo stem cell microenviroment and to study stem cell physiology and physio-pathology, in settings that better predict human cell biology, is becoming the object of much research effort. In this review we will detail the most relevant and recent advances in the field of biosensors and micro- and nano-technologies in general, highlighting advantages and disadvantages. Particular attention will be devoted to those applications employing stem cells as a sensing element.

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          Most cited references181

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          An integrated semiconductor device enabling non-optical genome sequencing.

          The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.
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            Geometric cues for directing the differentiation of mesenchymal stem cells.

            Significant efforts have been directed to understanding the factors that influence the lineage commitment of stem cells. This paper demonstrates that cell shape, independent of soluble factors, has a strong influence on the differentiation of human mesenchymal stem cells (MSCs) from bone marrow. When exposed to competing soluble differentiation signals, cells cultured in rectangles with increasing aspect ratio and in shapes with pentagonal symmetry but with different subcellular curvature-and with each occupying the same area-display different adipogenesis and osteogenesis profiles. The results reveal that geometric features that increase actomyosin contractility promote osteogenesis and are consistent with in vivo characteristics of the microenvironment of the differentiated cells. Cytoskeletal-disrupting pharmacological agents modulate shape-based trends in lineage commitment verifying the critical role of focal adhesion and myosin-generated contractility during differentiation. Microarray analysis and pathway inhibition studies suggest that contractile cells promote osteogenesis by enhancing c-Jun N-terminal kinase (JNK) and extracellular related kinase (ERK1/2) activation in conjunction with elevated wingless-type (Wnt) signaling. Taken together, this work points to the role that geometric shape cues can play in orchestrating the mechanochemical signals and paracrine/autocrine factors that can direct MSCs to appropriate fates.
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              Transmembrane crosstalk between the extracellular matrix--cytoskeleton crosstalk.

              Integrin-mediated cell adhesions provide dynamic, bidirectional links between the extracellular matrix and the cytoskeleton. Besides having central roles in cell migration and morphogenesis, focal adhesions and related structures convey information across the cell membrane, to regulate extracellular-matrix assembly, cell proliferation, differentiation, and death. This review describes integrin functions, mechanosensors, molecular switches and signal-transduction pathways activated and integrated by adhesion, with a unifying theme being the importance of local physical forces.
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                Author and article information

                Journal
                Sensors (Basel)
                Sensors (Basel)
                Sensors (Basel, Switzerland)
                Molecular Diversity Preservation International (MDPI)
                1424-8220
                2012
                19 November 2012
                : 12
                : 11
                : 15947-15982
                Affiliations
                [1 ] Department of Biology and CRIBI Biotechnology Centre, University of Padova, via U. Bassi 58/B, 35121 Padova, Italy; E-Mails: stefanoc@ 123456cribi.unipd.it (S.C.); paolom@ 123456cribi.unipd.it (P.M.)
                [2 ] Department of Biomedical Engineering, Columbia University, Vanderbilt Clinic Room 12-234, 630 West 168th Street, New York, NY 10032, USA; E-Mail: ec2438@ 123456columbia.edu
                [3 ] CLSE IBI-EPFL, Swiss Up Chair on Engineering, Laboratory of Life Sciences Electronics, Institute of Bioengineering, Ecole polytechnique Fédérale de Lausanne BM 2106, Station 17, CH-1015 Lausanne, Switzerland; E-Mail: carlotta.guiducci@ 123456epfl.ch
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: gerolamo.lanfranchi@ 123456unipd.it ; Tel.: +39-0498-276-221; Fax: +39-0498-276-159.
                [†]

                These authors contributed equally to this work.

                Article
                sensors-12-15947
                10.3390/s121115947
                3522993
                23202240
                5d383268-ff93-4a6b-980e-76248e03445e
                © 2012 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 license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 25 September 2012
                : 10 November 2012
                : 15 November 2012
                Categories
                Review

                Biomedical engineering
                cell biosensor,stem cell,microbioreactor,cell microarray,micropattern,cell microelectronic chip

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