Matrix promote mesenchymal stromal cell migration with improved deformation via nuclear stiffness decrease

Lin, Changjian; Tao, Bailong; Deng, Yiman; Shen, Xinkun; Wang, Rong; Lu, Lu; Peng, Zhihong; Xia, Zengzilu; Cai, Kaiyong

doi:10.1016/j.biomaterials.2019.119300

Cited by 32 publications

(32 citation statements)

References 68 publications

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“…When used in cell culture, alginate is usually covalently modified by cell-binding ligands or peptides, such as RGD and cadherins, to facilitate cell adhesion, owing to its lack of a cell adhesion domain 41 . Rigid alginate hydrogels can be easily fabricated by modifying the concentration of alginate or calcium chloride 38,42 , thus providing a tool for exploring the effects of matrix stiffness on the biological behaviors of CSCs. Because of these merits, alginate hydrogels are extensively used in constructing platforms for CSC enrichment and study 17,31,[35][36][37][38][39][40] .…”

Section: Biomaterials For Platform Constructionmentioning

confidence: 99%

“…Alginate hydrogels are commonly used to construct 3D structures with different stiffnesses, ranging from hundreds to thousands of Pascals, by modulation of the concentration of alginate 31,38 or the concentration of calcium chloride solution for cross-linking of alginate hydrogels 42 . Other natural or synthetic polymers, such as fibrin 50 and polyethylene glycol diacrylate (PEGDA) 45 , have also been used to establish 3D structures with different stiffness.…”

Section: Physical Cues Of Biomaterial-based Platformsmentioning

confidence: 99%

“…To minimize the concurrent adverse effects along with the change in stiffness, Liang et al 32 have developed a stiffness-controlled collagen-PEG gel and controlled the elastic modulus of the collagen hydrogel by incorporating varying amounts of PEG-diNHS into a pregel solution of collagen, thus allowing for the control of stiffness without significantly changing the permeability and number of cell adhesion motifs. By adjusting the concentration of Ca 2+ in alginate, Lin et al 42 have fabricated hydrogels with different stiffnesses without-a significant change in inner structures.…”

Section: Physical Cues Of Biomaterial-based Platformsmentioning

confidence: 99%

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Biomaterial-based platforms for cancer stem cell enrichment and study

Luo

Ding

et al. 2021

Cancer Biol. Med.

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Cancer stem cells (CSCs) are a relatively rare subpopulation of tumor cell with self-renewal and tumorigenesis capabilities. CSCs are associated with cancer recurrence, progression, and chemoradiotherapy resistance. Establishing a reliable platform for CSC enrichment and study is a prerequisite for understanding the characteristics of CSCs and discovering CSC-related therapeutic strategies. Certain strategies for CSC enrichment have been used in laboratory, particularly fluorescence-activated cell sorting (FACS) and mammosphere culture. However, these methods fail to recapitulate the in vivo chemical and physical conditions in tumors, thus potentially decreasing the malignancy of CSCs in culture and yielding unreliable research results. Accumulating research suggests the promise of a biomaterial-based three-dimensional (3D) strategy for CSC enrichment and study. This strategy has an advantage over conventional methods in simulating the tumor microenvironment, thus providing a more effective and predictive model for CSC laboratory research. In this review, we first briefly discuss the conventional methods for CSC enrichment and study. We then summarize the latest advances and challenges in biomaterial-based 3D CSC platforms. Design strategies for materials, morphology, and chemical and physical cues are highlighted to provide direction for the future construction of platforms for CSC enrichment and study.

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Section: Biomaterials For Platform Constructionmentioning

confidence: 99%

Section: Physical Cues Of Biomaterial-based Platformsmentioning

confidence: 99%

Section: Physical Cues Of Biomaterial-based Platformsmentioning

confidence: 99%

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Biomaterial-based platforms for cancer stem cell enrichment and study

Luo

Ding

et al. 2021

Cancer Biol. Med.

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“…[ 6–8 ] Recently, accumulating evidence has indicated that biophysical cues, especially ECM mechanics, greatly affect cell behavior and fate. [ 9–13 ] For example, hydrogels have been extensively used as synthetic ECMs for 3D cell culture and their elastic modulus (or stiffness) can influence cell spreading, [ 14,15 ] cell migration, [ 16 ] cell proliferation, [ 17 ] stemness, and differentiation of stem cells, [ 18–20 ] invasive phenotype of cancer cells, [ 21,22 ] and other important cell behaviors. However, native ECM generally exhibits dynamic mechanical properties and displays time‐dependent responses to deformation or mechanical loading, in terms of viscoelastic behaviors (e.g., stress relaxation and creep).…”

Section: Introductionmentioning

confidence: 99%

Viscoelastic Cell Microenvironment: Hydrogel‐Based Strategy for Recapitulating Dynamic ECM Mechanics

Han

Yang

et al. 2021

Adv Funct Materials

121

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The native extracellular matrix (ECM) generally exhibits dynamic mechanical properties and displays time‐dependent responses to deformation or mechanical loading, in terms of viscoelastic behaviors (e.g., stress relaxation and creep). Viscoelasticity of the ECM plays a critical role in development, homeostasis, and tissue regeneration, and its implication in disease progression has also been recognized recently. Hydrogels with tunable viscoelastic properties hold a great promise to recapitulate such time‐dependent mechanics found in native ECM, which have been recently used to regulate cell behavior and guide cell fate. Here the importance of tissue viscoelasticity is first highlighted, the molecular mechanisms of hydrogel viscoelasticity are summarized, and characterization techniques used at the macroscale and microscale are reviewed. Then, recent advances in developing novel hydrogels with tunable viscoelasticity through varying crosslinking strategies, engineering of viscoelastic cell microenvironment and its substantial effects on cell behavior and fate are described, and the underlying mechanobiology mechanisms are subsequently discussed. Finally, the ongoing challenges and future perspectives on the design and modulation of viscoelastic hydrogels and the mechanobiology mechanisms on cellular responses to viscoelastic cell microenvironment are proposed.

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“…[2][3][4][5] Usually, the nucleus is considered to be of spherical or ovoid shape, which is true for many types of cells. However, severe changes in nuclear morphology are also observed in various physiological processes such as malignant cell invasion, 6 smooth muscle cell contraction, 7 stem cell homing, 8 and embryo development. 9 As a cellular mechanosensor, changes in nuclear morphology are considered to directly affect chromatin reprogramming and genome functions that determine cell fate.…”

Section: Introductionmentioning

confidence: 99%

Chromatin Reprogramming via Contact Guidance-Induced Nuclear Deformation Promotes Stem Cell Differentiation

Agrawal¹,

Wang²,

Li³

et al. 2021

Preprint

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Efficient manipulation of cell fate is important for regenerative engineering applications. Lineage-specific differentiation of stem cells is particularly challenging due to their inherent plasticity. Engineered topographies may alter cellular plasticity through contact guidance. However, the ability to rationally design topographies to regulate phenotypic outcomes has been hindered in part by the lack of tools to quantify nanoscale chromatin structure reorganization in live cells. Herein we use micropillars, molecular, and nanostructural quantification tools to investigate how nuclear morphology in human mesenchymal stem cells (hMSCs) affects chromatin conformation and osteogenic differentiation. We show that micropillar-induced contact guidance is transduced via the cytoskeleton and impacts nuclear architecture, lamin A/C multimerization, histone modifications, and the 3-D conformation of chromatin within packing domains, a key regulator of transcriptional responsiveness. Micropillars repressed expression of genes associated with developmental processes and enhanced lineage-specific responsiveness, thereby decreasing cell plasticity and off-target differentiation, and facilitating osteogenic differentiation of hMSCs. Altogether, these findings reveal that chromatin reprogramming through contact guidance-induced nuclear deformation can be an efficient way to manipulate cell fate.

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Matrix promote mesenchymal stromal cell migration with improved deformation via nuclear stiffness decrease

Cited by 32 publications

References 68 publications

Biomaterial-based platforms for cancer stem cell enrichment and study

Biomaterial-based platforms for cancer stem cell enrichment and study

Viscoelastic Cell Microenvironment: Hydrogel‐Based Strategy for Recapitulating Dynamic ECM Mechanics

Chromatin Reprogramming via Contact Guidance-Induced Nuclear Deformation Promotes Stem Cell Differentiation

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