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Human mesenchymal stem cells in contact with their environment: surface characteristics and the integrin system.

Docheva D, Popov C, Mutschler W, Schieker M - J. Cell. Mol. Med. (2007 Jan-Feb)

Bottom Line: In this work, we will review the current state of knowledge on integrins and other adhesion molecules found to be expressed on MSCs.The discussed topics include the characteristics of MSCs and their clinical applications, integrins and their central role in cell-matrix attachment and migration, and comments on mobilization, differentiation and contribution to tumour development.Finally, by understanding the complex and fundamental pathways by which MSCs attach and migrate, it might be possible to fine-tune the strategies for effective and safe use of MSCs in regenerative therapies.

View Article: PubMed Central - PubMed

Affiliation: Experimental Surgery and Regenerative Medicine, Department of Surgery,Ludwig-Maximilians-University, Munich, Germany. Denitsa.Docheva@med.uni-muenchen.de

ABSTRACT
The identification of mesenchymal stem cells (MSCs) in adult human tissues and the disclosure of their self-renew-al and multi-lineage differentiation capabilities have provided exciting prospects for cell-based regeneration and tis-sue engineering. Although a considerable amount of data is available describing MSCs, there is still lack of information regarding the molecular mechanisms that govern their adhesion and migration. In this work, we will review the current state of knowledge on integrins and other adhesion molecules found to be expressed on MSCs. The discussed topics include the characteristics of MSCs and their clinical applications, integrins and their central role in cell-matrix attachment and migration, and comments on mobilization, differentiation and contribution to tumour development. Finally, by understanding the complex and fundamental pathways by which MSCs attach and migrate, it might be possible to fine-tune the strategies for effective and safe use of MSCs in regenerative therapies.

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A schematic model depicting the structure of focal adhesion and paxillin staining. (A and B) Fluorescent photomicrograph of human MSC showing the immuno-histological detection of paxillin, a multi-domain adaptor that recruits both structural and signalling molecules to focal adhesions (see gray outline in B). Primary anti-paxillin antibody (Cat. no. 1500-1, Epitomics, USA) was combined with secondary Alexa Fluor 488 antibody (in green), (Cat. no. A11034, Molecular Probes, Germany). Actin fibres and nucleus were stained respectively with Phalloidin (in red), (Cat. no. H-22284, Molecular Probes, Germany) and DAPI (in blue), (Cat. no. D1306, Molecular Probes, Germany). Bars: 50 μm (C) Focal adhesions are sites, where the heterodimeric (and) integrin receptors (depicted by the red and blue larger forms) engage with an extracellular matrix (ECM) protein (the shape in pink) and a cascade of integrin-, membrane-, actin- and signalling-associated molecules (represented as multi-colour dots). Besides having central roles in cell motility and cytoskeletal dynamics, focal adhesions convey information across the cell membrane to regulate cell proliferation, differentiation, gene expression and survival.
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fig02: A schematic model depicting the structure of focal adhesion and paxillin staining. (A and B) Fluorescent photomicrograph of human MSC showing the immuno-histological detection of paxillin, a multi-domain adaptor that recruits both structural and signalling molecules to focal adhesions (see gray outline in B). Primary anti-paxillin antibody (Cat. no. 1500-1, Epitomics, USA) was combined with secondary Alexa Fluor 488 antibody (in green), (Cat. no. A11034, Molecular Probes, Germany). Actin fibres and nucleus were stained respectively with Phalloidin (in red), (Cat. no. H-22284, Molecular Probes, Germany) and DAPI (in blue), (Cat. no. D1306, Molecular Probes, Germany). Bars: 50 μm (C) Focal adhesions are sites, where the heterodimeric (and) integrin receptors (depicted by the red and blue larger forms) engage with an extracellular matrix (ECM) protein (the shape in pink) and a cascade of integrin-, membrane-, actin- and signalling-associated molecules (represented as multi-colour dots). Besides having central roles in cell motility and cytoskeletal dynamics, focal adhesions convey information across the cell membrane to regulate cell proliferation, differentiation, gene expression and survival.

Mentions: Integrins are versatile receptors, transmitting inside-out and outside-in signals, which are crucial for the establishment of appropriate interactions between the exterior and interior of the cell. Many processes like cell morphology, motility, proliferation, differentiation and death are contingent on this incessant dialog.This bi-directional signalling requires, on one side, the integrin receptor to bind to ligands outside of the cell, and on the other to subcellular components. Many integrins bind beyond the cell to ECM proteins and thereby mediate cell–ECM interactions. Among ECM ligands for integrins are fibronectin, laminin, various collagens, tenascin, vitronectin and members of the SIBLINGs family (Small Integrin Binding LIgand, N-linked Glycoproteins), such as osteopontin, bone sialoprotein and dentin matrix protein 1 [45]. Other integrins bind to cell membrane receptors, mediating cell—cell adhesion. Such counter receptors are VCAM-1 and ICAM-1/2. In the third mode of interaction, for example, the αIIbβ3 integrin promotes the binding of platelets to one another through soluble, multivalent mediator molecules. Fibrinogen and von Willebrand factor function as the primary ligands for the platelet receptor {46}. Next, if we look at the inner face of the cell membrane, there are a lot of associated proteins, which can interact with the integrin transmembrane or cytoplasmic domains and their number is growing constantly. Once integrins are bound to their ligands, they move laterally in the plain of the membrane to form specialized clusters called focal adhesion sites. These specialized ECM attachment organelles and signalling centres assure substrate adhesion as well as targeted location of actin filaments and signalling components and hence they are essential for establishing cell polarity, directed cell migration, and maintaining cell growth and survival {47}. Some of these structural and functional features of focal adhesion are schematized in Fig. 2. In addition, we show staining for the focal adhesion component – paxillin in hMSCs.


Human mesenchymal stem cells in contact with their environment: surface characteristics and the integrin system.

Docheva D, Popov C, Mutschler W, Schieker M - J. Cell. Mol. Med. (2007 Jan-Feb)

A schematic model depicting the structure of focal adhesion and paxillin staining. (A and B) Fluorescent photomicrograph of human MSC showing the immuno-histological detection of paxillin, a multi-domain adaptor that recruits both structural and signalling molecules to focal adhesions (see gray outline in B). Primary anti-paxillin antibody (Cat. no. 1500-1, Epitomics, USA) was combined with secondary Alexa Fluor 488 antibody (in green), (Cat. no. A11034, Molecular Probes, Germany). Actin fibres and nucleus were stained respectively with Phalloidin (in red), (Cat. no. H-22284, Molecular Probes, Germany) and DAPI (in blue), (Cat. no. D1306, Molecular Probes, Germany). Bars: 50 μm (C) Focal adhesions are sites, where the heterodimeric (and) integrin receptors (depicted by the red and blue larger forms) engage with an extracellular matrix (ECM) protein (the shape in pink) and a cascade of integrin-, membrane-, actin- and signalling-associated molecules (represented as multi-colour dots). Besides having central roles in cell motility and cytoskeletal dynamics, focal adhesions convey information across the cell membrane to regulate cell proliferation, differentiation, gene expression and survival.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401218&req=5

fig02: A schematic model depicting the structure of focal adhesion and paxillin staining. (A and B) Fluorescent photomicrograph of human MSC showing the immuno-histological detection of paxillin, a multi-domain adaptor that recruits both structural and signalling molecules to focal adhesions (see gray outline in B). Primary anti-paxillin antibody (Cat. no. 1500-1, Epitomics, USA) was combined with secondary Alexa Fluor 488 antibody (in green), (Cat. no. A11034, Molecular Probes, Germany). Actin fibres and nucleus were stained respectively with Phalloidin (in red), (Cat. no. H-22284, Molecular Probes, Germany) and DAPI (in blue), (Cat. no. D1306, Molecular Probes, Germany). Bars: 50 μm (C) Focal adhesions are sites, where the heterodimeric (and) integrin receptors (depicted by the red and blue larger forms) engage with an extracellular matrix (ECM) protein (the shape in pink) and a cascade of integrin-, membrane-, actin- and signalling-associated molecules (represented as multi-colour dots). Besides having central roles in cell motility and cytoskeletal dynamics, focal adhesions convey information across the cell membrane to regulate cell proliferation, differentiation, gene expression and survival.
Mentions: Integrins are versatile receptors, transmitting inside-out and outside-in signals, which are crucial for the establishment of appropriate interactions between the exterior and interior of the cell. Many processes like cell morphology, motility, proliferation, differentiation and death are contingent on this incessant dialog.This bi-directional signalling requires, on one side, the integrin receptor to bind to ligands outside of the cell, and on the other to subcellular components. Many integrins bind beyond the cell to ECM proteins and thereby mediate cell–ECM interactions. Among ECM ligands for integrins are fibronectin, laminin, various collagens, tenascin, vitronectin and members of the SIBLINGs family (Small Integrin Binding LIgand, N-linked Glycoproteins), such as osteopontin, bone sialoprotein and dentin matrix protein 1 [45]. Other integrins bind to cell membrane receptors, mediating cell—cell adhesion. Such counter receptors are VCAM-1 and ICAM-1/2. In the third mode of interaction, for example, the αIIbβ3 integrin promotes the binding of platelets to one another through soluble, multivalent mediator molecules. Fibrinogen and von Willebrand factor function as the primary ligands for the platelet receptor {46}. Next, if we look at the inner face of the cell membrane, there are a lot of associated proteins, which can interact with the integrin transmembrane or cytoplasmic domains and their number is growing constantly. Once integrins are bound to their ligands, they move laterally in the plain of the membrane to form specialized clusters called focal adhesion sites. These specialized ECM attachment organelles and signalling centres assure substrate adhesion as well as targeted location of actin filaments and signalling components and hence they are essential for establishing cell polarity, directed cell migration, and maintaining cell growth and survival {47}. Some of these structural and functional features of focal adhesion are schematized in Fig. 2. In addition, we show staining for the focal adhesion component – paxillin in hMSCs.

Bottom Line: In this work, we will review the current state of knowledge on integrins and other adhesion molecules found to be expressed on MSCs.The discussed topics include the characteristics of MSCs and their clinical applications, integrins and their central role in cell-matrix attachment and migration, and comments on mobilization, differentiation and contribution to tumour development.Finally, by understanding the complex and fundamental pathways by which MSCs attach and migrate, it might be possible to fine-tune the strategies for effective and safe use of MSCs in regenerative therapies.

View Article: PubMed Central - PubMed

Affiliation: Experimental Surgery and Regenerative Medicine, Department of Surgery,Ludwig-Maximilians-University, Munich, Germany. Denitsa.Docheva@med.uni-muenchen.de

ABSTRACT
The identification of mesenchymal stem cells (MSCs) in adult human tissues and the disclosure of their self-renew-al and multi-lineage differentiation capabilities have provided exciting prospects for cell-based regeneration and tis-sue engineering. Although a considerable amount of data is available describing MSCs, there is still lack of information regarding the molecular mechanisms that govern their adhesion and migration. In this work, we will review the current state of knowledge on integrins and other adhesion molecules found to be expressed on MSCs. The discussed topics include the characteristics of MSCs and their clinical applications, integrins and their central role in cell-matrix attachment and migration, and comments on mobilization, differentiation and contribution to tumour development. Finally, by understanding the complex and fundamental pathways by which MSCs attach and migrate, it might be possible to fine-tune the strategies for effective and safe use of MSCs in regenerative therapies.

Show MeSH
Related in: MedlinePlus