Matrix elasticity directs stem cell lineage specification.

doi:10.1016/J.CELL.2006.06.044

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Matrix elasticity directs stem cell lineage specification.

Journal Article•DOI•

Matrix elasticity directs stem cell lineage specification.

Adam J. Engler¹, Shamik Sen¹, H. Lee Sweeney¹, Dennis E. Discher•Institutions (1)

University of Pennsylvania¹

25 Aug 2006-Cell (Cell Press)-Vol. 126, Iss: 4, pp 677-689

TL;DR: Naive mesenchymal stem cells are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity, consistent with the elasticity-insensitive commitment of differentiated cell types.

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About: This article is published in Cell.The article was published on 2006-08-25 and is currently open access. It has received 12204 citations till now. The article focuses on the topics: Mesenchymal stem cell differentiation & Stem cell fate determination.

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Journal Article•DOI•

Chemical Engineering Principles in the Field of Cell Mechanics

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Richard B. Dickinson¹, Tanmay P. Lele¹•Institutions (1)

University of Florida¹

08 Jun 2015-Industrial & Engineering Chemistry Research

TL;DR: It is argued that chemical engineering training is uniquely suited for fruitful research in the field of cell mechanics by discussing three examples in the research area.

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Abstract: The field of cell mechanics involves problems at the interface of mechanics, molecular transport, biochemical kinetics, thermodynamics, and cell biology. We argue that chemical engineering training is uniquely suited for fruitful research in the field by discussing three examples in the research area. Cell mechanics is already well-represented in many chemical engineering departments and promises to be a vibrant subarea in the profession.

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2 citations

Quantifying adhesive interactions between cells and extracellular matrix by single-cell force spectroscopy

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Anna Verena Taubenberger

04 May 2009

2 citations

Multiscale simulation of bone regeneration in ti ssue engineering processes

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Manuel Doblare Castellano

01 Jan 2008

2 citations

Book Chapter•DOI•

Interfacing Cell Surface Receptors to Hybrid Nanopatterned Surfaces: A Molecular Approach for Dissecting the Adhesion Machinery

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Julien Polleux¹•Institutions (1)

Max Planck Society¹

01 Jan 2010-Advances in Polymer Science

TL;DR: This chapter introduces biochemically modified gold surface models that have been designed to investigate cell adhesion, and specific emphasis is placed on micellar nanolithography, a technique enabling the preparation of gold nanopatterns.

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Abstract: Over the last 20 years, integrins have proven to be key players in connecting the internal cell machinery to the extracellular environment. Because the properties of the extracellular milieu strongly influence developmental programs triggered by integrin-mediated adhesion, the development of culture platforms with tunable chemical and physical properties is important for further understanding of the complexity of integrin functions. This chapter introduces biochemically modified gold surface models that have been designed to investigate cell adhesion. Specific emphasis is placed on micellar nanolithography, a technique enabling the preparation of gold nanopatterns. Such substrates are used as an analytical tool to control the activation of single-cell surface receptors for the study of integrin-mediated adhesion and signalling in a quantitative manner.

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2 citations

Dissertation•

Plasma rich in growth factors to treat Knee Osteoarthritis

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Sánchez Álvarez, José Miguel

01 Jun 2017

TL;DR: Los objetivos especificos delos trabajos realizados son los siguientes: Validar las inyecciones intraarticulares de PRP como un tratamiento seguro y eficaz para la artrosis de rodilla, y combinandoinfiltraciones intraartsiculare e intraoseas de Plasma rico en factores de crecimiento (PRP

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Abstract: En la tesis titulada Plasma Rich in Growth Factors to treat knee osteoarthritis se exponen 4 trabajosexperimentales basados en el uso del Plasma rico en factores de crecimiento. Los objetivos especificos delos trabajos realizados son los siguientes:1. Validar las inyecciones intraarticulares de PRP como un tratamiento seguro y eficaz para la artrosisde rodilla.2. Evaluar una nueva via para tratar la artrosis de rodilla, utilizando como diana la membrana sinovial,la superficie del cartilago articular, el liquido sinovial y el hueso subcondral, y combinandoinfiltraciones intraarticulares e intraoseas de Plasma rico en factores de crecimiento (PRP).3. Explorar la adecuacion del Liquido sinovial como fuente de celulas madre mesenquimales (CMMs)y sus respuestas a los mecanismos bilogicos implicados en los efectos de dos modalidades distintasde tratamiento de PRP en pacientes con artrosis: Inyecciones intraarticulares con la membranasinovial, la superfcicie del cartilago articular y el liquido sinovial como diana, o la combinacion deinyecciones intraarticulares e intraoseas, alcanzando por ultimo el hueso subcondral.

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2 citations

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Journal Article•DOI•

Multilineage Potential of Adult Human Mesenchymal Stem Cells

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Mark F. Pittenger, Alastair Morgan Mackay, Stephen C. Beck, Rama K. Jaiswal, Robin Douglas, Joseph D. Mosca, Mark Aaron Moorman, Donald William Jr. Ward Road Simonetti, Stewart Craig, Daniel R. Marshak¹ - Show less +6 more•Institutions (1)

Johns Hopkins University School of Medicine¹

02 Apr 1999-Science

TL;DR: Adult stem cells isolated from marrow aspirates of volunteer donors could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages.

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Abstract: Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.

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20,479 citations

"Matrix elasticity directs stem cell..." refers background or methods in this paper

...…Sweeney,1 and Dennis E. Discher1,2,3,4,* 1Pennsylvania Muscle Institute 2School of Engineering and Applied Science 3Cell & Molecular Biology Graduate Group 4Physics Graduate Group University of Pennsylvania, Philadelphia, PA 19104, USA *Contact: discher@seas.upenn.edu DOI 10.1016/j.cell.2006.06.044...
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...…specification of naive stem cells induced by soluble stimuli has been well described (Gang et al., 2004; Jaiswal et al., 1997; McBeath et al., 2004; Pittenger et al., 1999), but the results here report a strong and previously undocumented influence of microenvironment stiffness on stem cell…...
[...]
...The myoblast induction media used here (MIM, Table S2) is already known to promote myogenesis, with expression of MyoD, Myogenin, and skeletal muscle myosin heavy chain (Gang et al., 2004; Pittenger et al., 1999)....
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...Naive mesenchymal stem cells (MSCs) are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissuelevel elasticity....
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...…and have indeed been reported to differentiate into various anchorage-dependent cell types, including neurons, myoblasts, and osteoblasts (respectively, [Deng et al., 2005; Hofstetter et al., 2002; Kondo et al., 2005], [Pittenger et al., 1999], and [McBeath et al., 2004; Pittenger et al., 1999])....
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Journal Article•DOI•

Tissue Cells Feel and Respond to the Stiffness of Their Substrate

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Dennis E. Discher¹, Paul A. Janmey¹, Yu-li Wang²•Institutions (2)

University of Pennsylvania¹, University of Massachusetts Medical School²

18 Nov 2005-Science

TL;DR: An understanding of how tissue cells—including fibroblasts, myocytes, neurons, and other cell types—sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels with which elasticity can be tuned to approximate that of tissues.

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Abstract: Normal tissue cells are generally not viable when suspended in a fluid and are therefore said to be anchorage dependent. Such cells must adhere to a solid, but a solid can be as rigid as glass or softer than a baby's skin. The behavior of some cells on soft materials is characteristic of important phenotypes; for example, cell growth on soft agar gels is used to identify cancer cells. However, an understanding of how tissue cells-including fibroblasts, myocytes, neurons, and other cell types-sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels (or to other cells) with which elasticity can be tuned to approximate that of tissues. Key roles in molecular pathways are played by adhesion complexes and the actinmyosin cytoskeleton, whose contractile forces are transmitted through transcellular structures. The feedback of local matrix stiffness on cell state likely has important implications for development, differentiation, disease, and regeneration.

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5,889 citations

"Matrix elasticity directs stem cell..." refers background in this paper

...Such a wide variation in matrix stiffness for differentiated cells is known to influence focal-adhesion structure and the cytoskeleton (Bershadsky et al., 2003; Cukierman et al., 2001; Discher et al., 2005; Engler et al., 2004a; Lo et al., 2000; Pelham and Wang, 1997)....
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Journal Article•DOI•

CellProfiler: image analysis software for identifying and quantifying cell phenotypes

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Anne E. Carpenter¹, Thouis R. Jones¹, Michael R. Lamprecht¹, Colin Clarke¹, In Han Kang¹, Ola Friman², David A. Guertin¹, Joo Han Chang¹, Robert A. Lindquist¹, Jason Moffat¹, Polina Golland¹, David M. Sabatini¹ - Show less +8 more•Institutions (2)

Massachusetts Institute of Technology¹, Brigham and Women's Hospital²

31 Oct 2006-Genome Biology

TL;DR: The first free, open-source system designed for flexible, high-throughput cell image analysis, CellProfiler is described, which can address a variety of biological questions quantitatively.

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Abstract: Biologists can now prepare and image thousands of samples per day using automation, enabling chemical screens and functional genomics (for example, using RNA interference). Here we describe the first free, open-source system designed for flexible, high-throughput cell image analysis, CellProfiler. CellProfiler can address a variety of biological questions quantitatively, including standard assays (for example, cell count, size, per-cell protein levels) and complex morphological assays (for example, cell/organelle shape or subcellular patterns of DNA or protein staining).

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4,578 citations

Journal Article•DOI•

Cell shape, cytoskeletal tension, and rhoa regulate stem cell lineage commitment

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Rowena McBeath¹, Dana M. Pirone¹, Celeste M. Nelson¹, Kiran Bhadriraju¹, Christopher S. Chen¹ - Show less +1 more•Institutions (1)

Johns Hopkins University School of Medicine¹

01 Apr 2004-Developmental Cell

TL;DR: It is demonstrated that cell shape regulates commitment of human mesenchymal stem cells to adipocyte or osteoblast fate and mechanical cues experienced in developmental and adult contexts, embodied by cell shape, cytoskeletal tension, and RhoA signaling, are integral to the commitment of stem cell fate.

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3,995 citations

"Matrix elasticity directs stem cell..." refers background or result in this paper

...Similar results as above are found with a standard osteoblast induction media (OIM), which is known to promote cytoskeletal rearrangement and alkaline phosphatase production (Jaiswal et al., 1997; McBeath et al., 2004)....
[...]
...Lineage specification of naive stem cells induced by soluble stimuli has been well described (Gang et al., 2004; Jaiswal et al., 1997; McBeath et al., 2004; Pittenger et al., 1999), but the results here report a strong and previously undocumented influence of microenvironment stiffness on stem cell…...
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...(McBeath et al., 2004; Wang et al., 2002)....
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...Myosins in MSCs Couple Expression to Matrix Stiffness and Reveal a Key Role for NMM IIs Forces generated and/or imposed on the cell’s actin cytoskeleton have been postulated to influence differentiation (Engler et al., 2004a; Hinz et al., 2001; McBeath et al., 2004), but no past reports have hinted at strong, tissuedirected feedback of microenvironment elasticity on myosin expression or stem cell lineage specification....
[...]
...Lineage specification of naive stem cells induced by soluble stimuli has been well described (Gang et al., 2004; Jaiswal et al., 1997; McBeath et al., 2004; Pittenger et al., 1999), but the results here report a strong and previously undocumented influence of microenvironment stiffness on stem cell specification....
[...]

Journal Article•DOI•

Myofibroblasts and mechano-regulation of connective tissue remodelling

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James J. Tomasek¹, Giulio Gabbiani², Boris Hinz², Christine Chaponnier², Robert A. Brown³ - Show less +1 more•Institutions (3)

University of Oklahoma Health Sciences Center¹, University of Geneva², Royal National Orthopaedic Hospital³

01 May 2002-Nature Reviews Molecular Cell Biology

TL;DR: It is clear that the understanding of the myofibroblast — its origins, functions and molecular regulation — will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally.

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Abstract: During the past 20 years, it has become generally accepted that the modulation of fibroblastic cells towards the myofibroblastic phenotype, with acquisition of specialized contractile features, is essential for connective-tissue remodelling during normal and pathological wound healing. Yet the myofibroblast still remains one of the most enigmatic of cells, not least owing to its transient appearance in association with connective-tissue injury and to the difficulties in establishing its role in the production of tissue contracture. It is clear that our understanding of the myofibroblast its origins, functions and molecular regulation will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally.

...read moreread less

3,836 citations

"Matrix elasticity directs stem cell..." refers background in this paper

...…Sweeney,1 and Dennis E. Discher1,2,3,4,* 1Pennsylvania Muscle Institute 2School of Engineering and Applied Science 3Cell & Molecular Biology Graduate Group 4Physics Graduate Group University of Pennsylvania, Philadelphia, PA 19104, USA *Contact: discher@seas.upenn.edu DOI 10.1016/j.cell.2006.06.044...
[...]
...…gels and wrinkling-silicone sheets also suggest some responsiveness to the physical state of the matrix (Hinz et al., 2001; Nakagawa et al., 1989; Tomasek et al., 2002; Wozniak et al., 2003), but gel porosity and film topography complicate identification of possible contributions of substrate…...
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