Soft Material Approach to Induce Oxidative Stress in Mesenchymal Stem Cells for Functional Tissue Repair

Yang, Hai‐Bo; Nguyen, Kim Truc; Leong, David Tai; Tan, Nguan Soon; Tay, Chor Yong

doi:10.1021/acsami.6b09222

Cited by 44 publications

(60 citation statements)

References 50 publications

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“…126 Soft elastic materials in 2D, composed of fibronectin-coated polyacrylamide, induced reactive oxygen species (ROS) signaling in human bone marrow MSCs, whose conditioned media was shown to improve wound healing in vivo. 127 In vivo, soft alginate-based scaffolds with matrix metalloprotease (MMP)-cleavable domains improved MSC invasion into host tissue in mouse models compared to a stiffer material, and matrix production at the delivery site was significantly enhanced. 65 In engineering 3D human cardiac tissues, enhanced sarcomere [G] organization and contractile function resulted from the use of a chemically-crosslinked gelatin-PEG material with stiffness similar to native cardiac tissue that facilitated the ability of cells to establish cell-cell adhesions.…”

Section: Regenerative Medicine Applicationsmentioning

confidence: 99%

Mechanical forces direct stem cell behaviour in development and regeneration

Vining

Mooney

2017

Nat Rev Mol Cell Biol

1,228

958

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Stem cells and their local microenvironment, or niche, communicate through mechanical, cues to regulate cell fate and cell behaviour, and to guide developmental processes. During embryonic development, mechanical forces are involved in patterning and organogenesis. The physical environment of pluripotent stem cells regulates their differentiation and self-renewal. Mechanical and physical cues are also important in adult tissues, where adult stem cells require physical interactions with the extracellular matrix to maintain their potency. In vitro, synthetic models of the stem cell niche can be used to precisely control and manipulate the biophysical and biochemical properties of the stem cell microenvironment and examine how the mode and magnitude of mechanical cues, such as matrix stiffness or applied forces, direct stem cell differentiation and function. Fundamental insights on the mechanobiology of stem cells also inform the design of artificial niches to support stem cells for regenerative therapies.

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Section: Regenerative Medicine Applicationsmentioning

confidence: 99%

Mechanical forces direct stem cell behaviour in development and regeneration

Vining

Mooney

2017

Nat Rev Mol Cell Biol

1,228

958

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show abstract

“…Stiffness has been known as one of the most important biophysical cues to modulate cell and tissue behaviors . From dynamic perspective, both normal and diseased tissues exhibit spatiotemporal changing of elasticities during their development, regeneration, and ageing .…”

Section: Introductionmentioning

confidence: 99%

Mechanical Adaptability of the MMP‐Responsive Film Improves the Functionality of Endothelial Cell Monolayer

Chang

et al. 2017

Adv Healthcare Materials

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Extracellular matrix and cells are inherent in coordinating and adapting to each other during all physiological and pathological processes. Synthetic materials, however, show rarely reciprocal and spatiotemporal responses to cells, and lacking self-adapting properties as well. Here, a mechanical adaptability based on the matrix metalloproteinase (MMPs) sensitive polyelectrolyte film is reported. Poly-lysine (PLL) and methacrylated hyaluronic acid (HA-MA) nanolayers are employed to build the thin film through the layer-by-layer assembly, and it is further crosslinked using MMP sensitive peptides, which endows the films with changeable mechanical properties in response to MMPs. It is demonstrated that stiffness of the (PLL/HA-MA) films increases with the crosslinking, and then decreases in response to a treatment of enzyme. Consequently, the crosslinked (PLL/HA-MA) films reveal effective growth of endothelial cells (ECs), leading to fast formation of EC monolayer. Importantly, significantly improved endothelial function of the EC monolayer, which is characterized by integrity, biomolecules release, expression of function related gene, and antithrombotic properties, is achieved along with the decrosslinking of the film because of EC-secreted MMPs. These results suggest that mechanical adaptability of substrate in Young's modulus plays a significant role in endothelial progression, which shows great application potential in tissue engineering, regenerative medicine, and organ-on-a-chip.

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“…The function of the MSC secretome is activated by local micro-environmental cues that modulate MSC differentiation as well as that of subsidiary tissues [17,18]. Changes in growth factors/cytokines [19,20], oxygen tension [21,22], or environmental mechanical cues arising from the extracellular matrix [23,24] or substrate stiffness [25,26] have been shown to directly influence MSC paracrine activity. Scaffolds of distinct composition and cytoarchitecture influence how the cellular mechanotransduction machinery translates environmental mechanical and chemical cues into transcriptional and paracrine responses.…”

Section: Introductionmentioning

confidence: 99%

Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration

et al. 2020

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Background: The mesenchymal stem cell (MSC) secretome, via the combined actions of its plethora of biologically active factors, is capable of orchestrating the regenerative responses of numerous tissues by both eliciting and amplifying biological responses within recipient cells. MSCs are "environmentally responsive" to local micro-environmental cues and biophysical perturbations, influencing their differentiation as well as secretion of bioactive factors. We have previously shown that exposures of MSCs to pulsed electromagnetic fields (PEMFs) enhanced MSC chondrogenesis. Here, we investigate the influence of PEMF exposure over the paracrine activity of MSCs and its significance to cartilage regeneration.Methods: Conditioned medium (CM) was generated from MSCs subjected to either 3D or 2D culturing platforms, with or without PEMF exposure. The paracrine effects of CM over chondrocytes and MSC chondrogenesis, migration and proliferation, as well as the inflammatory status and induced apoptosis in chondrocytes and MSCs was assessed.Results: We show that benefits of magnetic field stimulation over MSC-derived chondrogenesis can be partly ascribed to its ability to modulate the MSC secretome. MSCs cultured on either 2D or 3D platforms displayed distinct magnetic sensitivities, whereby MSCs grown in 2D or 3D platforms responded most favorably to PEMF exposure at 2 mT and 3 mT amplitudes, respectively. Ten minutes of PEMF exposure was sufficient to substantially augment the chondrogenic potential of MSC-derived CM generated from either platform. Furthermore, PEMF-induced CM was capable of enhancing the migration of chondrocytes and MSCs as well as mitigating cellular inflammation and apoptosis. Conclusions:The findings reported here demonstrate that PEMF stimulation is capable of modulating the paracrine function of MSCs for the enhancement and re-establishment of cartilage regeneration in states of cellular stress. The PEMF-induced modulation of the MSC-derived paracrine function for directed biological responses in recipient cells or tissues has broad clinical and practical ramifications with high translational value across numerous clinical applications.

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Soft Material Approach to Induce Oxidative Stress in Mesenchymal Stem Cells for Functional Tissue Repair

Cited by 44 publications

References 50 publications

Mechanical forces direct stem cell behaviour in development and regeneration

Mechanical forces direct stem cell behaviour in development and regeneration

Mechanical Adaptability of the MMP‐Responsive Film Improves the Functionality of Endothelial Cell Monolayer

Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration

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