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      Extracellular matrix: A dynamic microenvironment for stem cell niche

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          Abstract

          Background

          Extracellular matrix (ECM) is a dynamic and complex environment characterized by biophysical, mechanical and biochemical properties specific for each tissue and able to regulate cell behavior. Stem cells have a key role in the maintenance and regeneration of tissues and they are located in a specific microenvironment, defined as niche.

          Scope of review

          We overview the progresses that have been made in elucidating stem cell niches and discuss the mechanisms by which ECM affects stem cell behavior. We also summarize the current tools and experimental models for studying ECM–stem cell interactions.

          Major conclusions

          ECM represents an essential player in stem cell niche, since it can directly or indirectly modulate the maintenance, proliferation, self-renewal and differentiation of stem cells. Several ECM molecules play regulatory functions for different types of stem cells, and based on its molecular composition the ECM can be deposited and finely tuned for providing the most appropriate niche for stem cells in the various tissues. Engineered biomaterials able to mimic the in vivo characteristics of stem cell niche provide suitable in vitro tools for dissecting the different roles exerted by the ECM and its molecular components on stem cell behavior.

          General significance

          ECM is a key component of stem cell niches and is involved in various aspects of stem cell behavior, thus having a major impact on tissue homeostasis and regeneration under physiological and pathological conditions. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.

          Highlights

          • Stem cells have a key role in the maintenance and regeneration of tissues.

          • The extracellular matrix is a critical regulator of stem cell function.

          • Stem cells reside in a dynamic and specialized microenvironment denoted as niche.

          • The extracellular matrix represents an essential component of stem cell niches.

          • Bioengineered niches can be used for investigating stem cell–matrix interactions.

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          Most cited references158

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          Mechanisms and functional implications of adult neurogenesis.

          The generation of new neurons is sustained throughout adulthood in the mammalian brain due to the proliferation and differentiation of adult neural stem cells. In this review, we discuss the factors that regulate proliferation and fate determination of adult neural stem cells and describe recent studies concerning the integration of newborn neurons into the existing neural circuitry. We further address the potential significance of adult neurogenesis in memory, depression, and neurodegenerative disorders such as Alzheimer's and Parkinson's disease.
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            Designing cell-compatible hydrogels for biomedical applications.

            Hydrogels are polymeric materials distinguished by high water content and diverse physical properties. They can be engineered to resemble the extracellular environment of the body's tissues in ways that enable their use in medical implants, biosensors, and drug-delivery devices. Cell-compatible hydrogels are designed by using a strategy of coordinated control over physical properties and bioactivity to influence specific interactions with cellular systems, including spatial and temporal patterns of biochemical and biomechanical cues known to modulate cell behavior. Important new discoveries in stem cell research, cancer biology, and cellular morphogenesis have been realized with model hydrogel systems premised on these designs. Basic and clinical applications for hydrogels in cell therapy, tissue engineering, and biomedical research continue to drive design improvements using performance-based materials engineering paradigms.
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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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                Author and article information

                Contributors
                Journal
                Biochim Biophys Acta
                Biochim. Biophys. Acta
                Biochimica et Biophysica Acta
                Elsevier Pub. Co
                0006-3002
                1 August 2014
                August 2014
                : 1840
                : 8
                : 2506-2519
                Affiliations
                Department of Molecular Medicine, University of Padova, 35131 Padova, Italy
                Author notes
                [* ]Corresponding authors. Tel.: + 39 049 8276084; fax: + 39 049 8276079. annaurciolo@ 123456hotmail.com bonaldo@ 123456bio.unipd.it
                [1]

                These authors contributed equally to this work.

                Article
                S0304-4165(14)00012-9
                10.1016/j.bbagen.2014.01.010
                4081568
                24418517
                4835317c-2e52-4693-8f3b-970cee103770
                © 2014 Published by Elsevier B.V.
                History
                : 5 November 2013
                : 5 January 2014
                : 6 January 2014
                Categories
                Review

                Biochemistry
                ecm, extracellular matrix,cbcs, crypt base columnar cells,hfscs, hair follicle stem cells,hscs, hematopoietic stem cells,iscs, intestinal stem cells,nscs, neural stem cells,sgz, subgranular zone,svz, subventricular zone,extracellular matrix,stem cell,stem cell niche,cell receptor,growth factor,tissue engineering

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