A simple elastic membrane‐based microfluidic chip for the proliferation and differentiation of mesenchymal stem cells under tensile stress

Gao, Xinghua; Zhang, Xu; Tong, Huiyu; Lin, Baiquan; Qin, Jianhua

doi:10.1002/elps.201100237

Cited by 18 publications

(8 citation statements)

References 18 publications

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“…Therefore, such spatiotemporal variations in the mechanical microenvironment of bone marrow due to physiological activity or external stimulation may have significant effects on bone mesenchymal stem cell (BMSC) fate decisions . Actually, accumulating evidence has shown that MSCs can respond to diverse dynamic mechanical forces (e.g., tensile stress, compressive stress, and shear stress) and can be directed into specific differentiation pathways. For example, cyclic tensile stress can induce differentiation of MSCs toward a smooth muscle cell phenotype or a myogenic phenotype, whereas cyclic compressive loading can lead to upregulated expression of typical markers of chondrogenic differentiation .…”

Section: Native Spatiotemporal Mechanical Microenvironments Of Stem Cmentioning

confidence: 99%

3D Spatiotemporal Mechanical Microenvironment: A Hydrogel‐Based Platform for Guiding Stem Cell Fate

et al. 2018

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Stem cells hold great promise for widespread biomedical applications, for which stem cell fate needs to be well tailored. Besides biochemical cues, accumulating evidence has demonstrated that spatiotemporal biophysical cues (especially mechanical cues) imposed by cell microenvironments also critically impact on the stem cell fate. As such, various biomaterials, especially hydrogels due to their tunable physicochemical properties and advanced fabrication approaches, are developed to spatiotemporally manipulate biophysical cues in vitro so as to recapitulate the 3D mechanical microenvironment where stem cells reside in vivo. Here, the main mechanical cues that stem cells experience in their native microenvironment are summarized. Then, recent advances in the design of hydrogel materials with spatiotemporally tunable mechanical properties for engineering 3D the spatiotemporal mechanical microenvironment of stem cells are highlighted. These in vitro engineered spatiotemporal mechanical microenvironments are crucial for guiding stem cell fate and their potential biomedical applications are subsequently discussed. Finally, the challenges and future perspectives are presented.

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Section: Native Spatiotemporal Mechanical Microenvironments Of Stem Cmentioning

confidence: 99%

3D Spatiotemporal Mechanical Microenvironment: A Hydrogel‐Based Platform for Guiding Stem Cell Fate

et al. 2018

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“…The growing evidences show that MSCs can respond to various mechanical stimuli, 6 such as compressive loading, 7,8 tensile stress, 9,10 and shear stress. [11][12][13] Typically, the shear flow in bone microenvironment can be roughly divided into two types, vascular and lumen flow and interstitial flow.…”

Section: Regulation Of Cell Migration and Osteogenic Differentiation mentioning

confidence: 99%

Regulation of cell migration and osteogenic differentiation in mesenchymal stem cells under extremely low fluidic shear stress

Gao

Zhang

et al. 2014

Biomicrofluidics

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Mesenchymal stem cells (MSCs) are multipotent stem cells predominantly obtained from bone marrow, which are sensitive to mechanical loadings in physiological microenvironment. However, how the MSCs sense and respond to extremely low fluidic shear stress analogous to interstitial flow in vivo is poorly understood. In this work, we present a functional microfluidic device to examine the migration and differentiation behaviors of MSCs in response to multiple orders of physiologically relevant interstitial flow levels. The different magnitudes of fluid flow-induced shear stress were produced by a hydraulic resistance-based microfluidic perfusion system consisting of a microchannel network and a parallel of uniform cell culture chambers. By changing the length and width of the flow-in channels, the multiple magnitudes of low shear stresses could be generated ranging from ∼10−5 to ∼10−2 dyne/cm2. We demonstrated enhanced significant F-actin expression and cell migration in MSCs under applied fluidic shear stress at ∼10−2 dyne/cm2. We also demonstrated a significant osteogenic differentiation under this interstitial level of slow flows from ∼10−2 to ∼10−4 dyne/cm2 in MSCs by analyzing alkaline phosphatase activity and osteopontin staining. Moreover, cytochalasin D and Rho-inhibitor Y-27632 significantly reduced the cytoskeleton F-actin expression and osteogenic differentiation in MSCs, indicating the mediated mechanical responses of MSCs under extremely low fluidic shear stress, possibly as a consequence of Rho-associated kinase pathway. The established microfluidic perfusion system with multiple shear-flow capabilities is simple and easy to operate, providing a flexible platform for studying the responses of diverse types of cells to the multiple interstitial flow levels in a single assay.

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“…As another example with a higher degree of complexity, Gao X. et al designed a membrane-based microfluidic chip to study the effect of shear stress on proliferation and differentiation of MSCs, when it is induced by cyclic tensile stress on a cell membrane ( Gao et al, 2011 ). The chip was composed by three polydimethylsiloxane (PDMS) layers: a top layer containing cell culture channels, a bottom layer containing gas control channels, and a middle elastic membrane, sandwiched between the two layers, irreversibly sealed by oxygen plasma.…”

Section: Mimicking and Studying The Biological Features Of Bone Microenvironment By Using Perfused Macro/milli/micro Bioreactorsmentioning

confidence: 99%

Perfused Platforms to Mimic Bone Microenvironment at the Macro/Milli/Microscale: Pros and Cons

Lipreri

Baldini

Graziani

et al. 2022

Front. Cell Dev. Biol.

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As life expectancy increases, the population experiences progressive ageing. Ageing, in turn, is connected to an increase in bone-related diseases (i.e., osteoporosis and increased risk of fractures). Hence, the search for new approaches to study the occurrence of bone-related diseases and to develop new drugs for their prevention and treatment becomes more pressing. However, to date, a reliable in vitro model that can fully recapitulate the characteristics of bone tissue, either in physiological or altered conditions, is not available. Indeed, current methods for modelling normal and pathological bone are poor predictors of treatment outcomes in humans, as they fail to mimic the in vivo cellular microenvironment and tissue complexity. Bone, in fact, is a dynamic network including differently specialized cells and the extracellular matrix, constantly subjected to external and internal stimuli. To this regard, perfused vascularized models are a novel field of investigation that can offer a new technological approach to overcome the limitations of traditional cell culture methods. It allows the combination of perfusion, mechanical and biochemical stimuli, biological cues, biomaterials (mimicking the extracellular matrix of bone), and multiple cell types. This review will discuss macro, milli, and microscale perfused devices designed to model bone structure and microenvironment, focusing on the role of perfusion and encompassing different degrees of complexity. These devices are a very first, though promising, step for the development of 3D in vitro platforms for preclinical screening of novel anabolic or anti-catabolic therapeutic approaches to improve bone health.

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A simple elastic membrane‐based microfluidic chip for the proliferation and differentiation of mesenchymal stem cells under tensile stress

Cited by 18 publications

References 18 publications

3D Spatiotemporal Mechanical Microenvironment: A Hydrogel‐Based Platform for Guiding Stem Cell Fate

3D Spatiotemporal Mechanical Microenvironment: A Hydrogel‐Based Platform for Guiding Stem Cell Fate

Regulation of cell migration and osteogenic differentiation in mesenchymal stem cells under extremely low fluidic shear stress

Perfused Platforms to Mimic Bone Microenvironment at the Macro/Milli/Microscale: Pros and Cons

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