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      Extracellular matrix: a dynamic microenvironment for stem cell niche.

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          Abstract

          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.

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          Mechanisms and functional implications of adult neurogenesis.

          Chunmei Zhao, Wei Deng, Fred Gage (2008)
          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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            IFNalpha activates dormant haematopoietic stem cells in vivo.

            Marieke Essers, Sandra Offner, William E. Blanco-Bose … (2009)
            Maintenance of the blood system is dependent on dormant haematopoietic stem cells (HSCs) with long-term self-renewal capacity. After injury these cells are induced to proliferate to quickly re-establish homeostasis. The signalling molecules promoting the exit of HSCs out of the dormant stage remain largely unknown. Here we show that in response to treatment of mice with interferon-alpha (IFNalpha), HSCs efficiently exit G(0) and enter an active cell cycle. HSCs respond to IFNalpha treatment by the increased phosphorylation of STAT1 and PKB/Akt (also known as AKT1), the expression of IFNalpha target genes, and the upregulation of stem cell antigen-1 (Sca-1, also known as LY6A). HSCs lacking the IFNalpha/beta receptor (IFNAR), STAT1 (ref. 3) or Sca-1 (ref. 4) are insensitive to IFNalpha stimulation, demonstrating that STAT1 and Sca-1 mediate IFNalpha-induced HSC proliferation. Although dormant HSCs are resistant to the anti-proliferative chemotherapeutic agent 5-fluoro-uracil, HSCs pre-treated (primed) with IFNalpha and thus induced to proliferate are efficiently eliminated by 5-fluoro-uracil exposure in vivo. Conversely, HSCs chronically activated by IFNalpha are functionally compromised and are rapidly out-competed by non-activatable Ifnar(-/-) cells in competitive repopulation assays. Whereas chronic activation of the IFNalpha pathway in HSCs impairs their function, acute IFNalpha treatment promotes the proliferation of dormant HSCs in vivo. These data may help to clarify the so far unexplained clinical effects of IFNalpha on leukaemic cells, and raise the possibility for new applications of type I interferons to target cancer stem cells.
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              Geometric cues for directing the differentiation of mesenchymal stem cells.

              Kristopher A. Kilian, Branimir Bugarija, Bruce T. Lahn … (2010)
              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

                Journal
                Journal ID (iso-abbrev): Biochim Biophys Acta
                Title: Biochimica et biophysica acta
                Publisher: Elsevier BV
                ISSN: 0006-3002
                ISSN (Print): 0006-3002
                Publication date (Electronic): Aug 2014
                Volume: 1840
                Issue: 8
                Affiliations
                [1 ] Department of Molecular Medicine, University of Padova, 35131 Padova, Italy.
                [2 ] Department of Molecular Medicine, University of Padova, 35131 Padova, Italy. Electronic address: annaurciolo@hotmail.com.
                [3 ] Department of Molecular Medicine, University of Padova, 35131 Padova, Italy. Electronic address: bonaldo@bio.unipd.it.
                Article
                Publisher Item ID: S0304-4165(14)00012-9
                DOI: 10.1016/j.bbagen.2014.01.010
                PMC ID: 4081568
                PubMed ID: 24418517
                SO-VID: 4835317c-2e52-4693-8f3b-970cee103770
                Copyright © Copyright © 2014. Published by Elsevier B.V.
                History

                Keywords: Cell receptor,Extracellular matrix,Growth factor,Stem cell,Stem cell niche,Tissue engineering
                Data availability:
                Keywords: Cell receptor, Extracellular matrix, Growth factor, Stem cell, Stem cell niche, Tissue engineering

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