Stem cells, microenvironment mechanics, and growth factor activation

Tenney, Robert; Discher, Dennis E.

doi:10.1016/j.ceb.2009.06.003

Cited by 95 publications

(73 citation statements)

References 52 publications

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“…The impact of forces and mechanical environment on the structure and function of cells and tissues has been increasingly documented in many recent studies and summarized in recent reviews (Mammoto and Ingber, 2010;Tenney and Discher, 2009;Vogel and Sheetz, 2009). Many of these research efforts have been directed at demonstrating that physical features such as stiffness are direct stimuli for specific cellular responses, rather than attributable to biochemical differences in the substrates.…”

Section: Introductionmentioning

confidence: 99%

“…In this Commentary, we discuss the differences between physical and chemical stimuli that can influence cell and tissue function, and consider the fundamental mechanisms that might enable cells to measure the stiffness of the extracellular matrix and of neighboring cells. Candidate proteins and signals that are involved in sensing or responding to forces and might also be relevant to stiffness sensing have been well discussed in other recent reviews (Koivusalo et al, 2009;Kumar and Weaver, 2009;Mammoto and Ingber, 2010;Tenney and Discher, 2009;Vogel and Sheetz, 2009). …”

Section: Introductionmentioning

confidence: 99%

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Mechanisms of mechanical signaling in development and disease

Janmey

Miller

2011

Journal of Cell Science

408

332

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SummaryThe responses of cells to chemical signals are relatively well characterized and understood. Cells also respond to mechanical signals in the form of externally applied force and forces generated by cell-matrix and cell-cell contacts. Many features of cell function that are generally considered to be under the control of chemical stimuli, such as motility, proliferation, differentiation and survival, can also be altered by changes in the stiffness of the substrate to which the cells are adhered, even when their chemical environment remains unchanged. Many examples from clinical and whole animal studies have shown that changes in tissue stiffness are related to specific disease characteristics and that efforts to restore normal tissue mechanics have the potential to reverse or prevent cell dysfunction and disease. How cells detect stiffness is largely unknown, but the cellular structures that measure stiffness and the general principles by which they work are beginning to be revealed. This Commentary highlights selected recent reports of mechanical signaling during disease development, discusses open questions regarding the physical mechanisms by which cells sense stiffness, and examines the relationship between studies in vitro on flat substrates and the more complex three-dimensional setting in vivo.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mechanisms of mechanical signaling in development and disease

Janmey

Miller

2011

Journal of Cell Science

408

332

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“…Especially during development, epithelial cells grow, divide and move, leading to a dynamic reorganisation of the entire tissue. This process is regulated by a complex set of chemical and mechanical signalling pathways [1][2][3][4] that control cell shapes and cell-cell contacts. How the regulation of cell-cell interactions is transmitted to the tissue-level organisation is still a topic of active research.…”

Section: Introductionmentioning

confidence: 99%

Cell division and death inhibit glassy behaviour of confluent tissues

et al. 2017

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We investigate the effects of cell division and apopotosis on collective dynamics in two-dimensional epithelial tissues. Our model includes three key ingredients observed across many epithelia, namely cell-cell adhesion, cell death and a cell division process that depends on the surrounding environment. We show a rich non-equilibrium phase diagram depending on the ratio of cell death to cell division and on the adhesion strength. For large apopotosis rates, cells die out and the tissue disintegrates. As the death rate decreases, however, we show, consecutively, the existence of a gas-like phase, a gel-like phase, and a dense confluent (tissue) phase. Most striking is the observation that the tissue is self-melting through its own internal activity, ruling out the existence of any glassy phase.

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“…Therefore, a biomimetic microenvironment that can guide cell differentiation is a very powerful tool in regenerative medicine. 25 In this study, we built an artificial niche for vascular tissue formation from BMNCs by combining the soft elastomeric PGS and platelets and plasma. We found that diluted plateletpoor plasma and platelets could be coated onto the porous structure of the PGS scaffolds.…”

Section: Discussionmentioning

confidence: 99%

Artificial Niche Combining Elastomeric Substrate and Platelets Guides Vascular Differentiation of Bone Marrow Mononuclear Cells

Allen

Gao

et al. 2011

Tissue Engineering Part A

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Bone marrow-derived progenitor cells are promising cell sources for vascular tissue engineering. However, conventional bone marrow mesenchymal stem cell expansion and induction strategies require plating on tissue culture plastic, a stiff substrate that may itself influence cell differentiation. Direct scaffold seeding avoids plating on plastic; to the best of our knowledge, there is no report of any scaffold that induces the differentiation of bone marrow mononuclear cells (BMNCs) to vascular cells in vitro. In this study, we hypothesize that an elastomeric scaffold with adsorbed plasma proteins and platelets will induce differentiation of BMNCs to vascular cells and promote vascular tissue formation by combining soft tissue mechanical properties with platelet-mediated tissue repairing signals. To test our hypothesis, we directly seeded rat primary BMNCs in four types of scaffolds: poly(lactide-co-glycolide), elastomeric poly(glycerol sebacate) (PGS), platelet-poor plasma-coated PGS, and PGS coated by plasma supplemented with platelets. After 21 days of culture, osteochondral differentiation of cells in poly(lactide-co-glycolide) was detected, but most of the adhered cells on the surface of all PGS scaffolds expressed calponin-I and a-smooth muscle actin, suggesting smooth muscle differentiation. Cells in PGS scaffolds also produced significant amount of collagen and elastin. Further, plasma coating improves seeding efficiency, and platelet increases proliferation, the number of differentiated cells, and extracellular matrix content. Thus, the artificial niche composed of platelets, plasma, and PGS is promising for artery tissue engineering using BMNCs.

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Stem cells, microenvironment mechanics, and growth factor activation

Cited by 95 publications

References 52 publications

Mechanisms of mechanical signaling in development and disease

Mechanisms of mechanical signaling in development and disease

Cell division and death inhibit glassy behaviour of confluent tissues

Artificial Niche Combining Elastomeric Substrate and Platelets Guides Vascular Differentiation of Bone Marrow Mononuclear Cells

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