Micro-patterned cell populations as advanced pharmaceutical drugs with precise functional control

Che, Hui; Selig, Mischa; Rolauffs, Bernd

doi:10.1016/j.addr.2022.114169

Cited by 12 publications

(10 citation statements)

References 269 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Micropatterns were prepared by photolithography. 37 First, azidophenyl-derived poly(vinyl alcohol) (AzPhPVA) was synthesized by binding 4-azidobenzoic acid with some hydroxyl groups in poly(vinyl alcohol) (PVA) as previously reported. 38 Briefly, 11.3 mM dicyclohexylcarbodiimide (DCC, Watanabe Chemical Industries, Ltd., Japan) solution in dimethyl sulfoxide (DMSO, Wako Pure Chemical Industries, Ltd., Japan) was added dropwise into 11.3 mM 4-azidobenzoic acid (dissolved in DMSO, Wako Pure Chemical Industries, Ltd., Japan) under stirring at room temperature in the dark.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

See 1 more Smart Citation

How Hydrogel Stiffness Affects Adipogenic Differentiation of Mesenchymal Stem Cells under Controlled Morphology

Zheng

Yoshitomi

et al. 2023

ACS Appl. Bio Mater.

View full text Add to dashboard Cite

Matrix stiffness has been disclosed as an essential regulator of cell fate. However, it is barely studied how the matrix stiffness affects stem cell functions when cell morphology changes. Thus, in this study, the effect of hydrogel stiffness on adipogenic differentiation of human bone-marrow-derived mesenchymal stem cells (hMSCs) with controlled morphology was investigated. Micropatterns of different size and elongation were prepared by a photolithographical micropatterning technique. The hMSCs were cultured on the micropatterns and showed a different spreading area and elongation following the geometry of the underlying micropatterns. The cells with controlled morphology were embedded in agarose hydrogels of different stiffnesses. The cells showed a different level of adipogenic differentiation that was dependent on both hydrogel stiffness and cell morphology. Adipogenic differentiation became strong when the cell spreading area decreased and hydrogel stiffness increased. Adipogenic differentiation did not change with cell elongation. Therefore, cell spreading area and hydrogel stiffness could synergistically affect adipogenic differentiation of hMSCs, while cell elongation did not affect adipogenic differentiation. A change of cell morphology and hydrogel stiffness was accompanied by actin filament alignment that was strongly related to adipogenic differentiation. The results indicated that cell morphology could affect cellular sensitivity to hydrogel stiffness. The results will provide useful information for the elucidation of the interaction of stem cells and their microenvironmental biomechanical cues.

show abstract

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…The experimental design is shown in Scheme . Micropatterns were prepared by photolithography . First, azidophenyl-derived poly(vinyl alcohol) (AzPhPVA) was synthesized by binding 4-azidobenzoic acid with some hydroxyl groups in poly(vinyl alcohol) (PVA) as previously reported .…”

Section: Methodsmentioning

confidence: 99%

How Hydrogel Stiffness Affects Adipogenic Differentiation of Mesenchymal Stem Cells under Controlled Morphology

Zheng

Yoshitomi

et al. 2023

ACS Appl. Bio Mater.

View full text Add to dashboard Cite

show abstract

“…The formation and arrangement of cellular adhesion proteins can be regulated by cell density-dependent cell-cell interactions and cellular microenvironment. [41][42][43] Focal adhesion (FA) serves as the most important adhesion proteins of cells to affect the cell behaviors. 44 Herein, the cells cultured in various microholes reorganized their FAs to deliver biophysical signals from the extracellular microenvironment into the cells; thus, FA acted as the mechanosensor between the extracellular matrix (ECM) and the cytoskeleton to affect the nuclear functions (Fig.…”

Section: Formation Of Heterogeneous Focal Adhesion In Micropatternsmentioning

confidence: 99%

Regulation of micropatterned curvature-dependent FA heterogeneity on cytoskeleton tension and nuclear DNA synthesis of malignant breast cancer cells

Wang

Chen

et al. 2023

J. Mater. Chem. B

View full text Add to dashboard Cite

show abstract

“…Quantitative cell shape in particular has become an important aspect of cell phenotype. Indeed, the morphological status of cells can be linked to fundamental cell functions ( 33 ) such as cell proliferation ( 34 ), cell differentiation ( 35 – 39 ), cell cycle progression ( 40 ), cell spreading and cell migration ( 41 ), the invasive potential of cancerous cells ( 42 ), as well as inflammation ( 43 , 44 ). Thus, the morphological status of cells can be utilized as a “morphological fingerprint” ( 30 ) and quantifying single cell morphology using high-throughput techniques can hence be useful for describing and better understanding the impact of biochemical ( 45 ) and biophysical ( 45 – 48 ) stimuli on cells.…”

Section: Introductionmentioning

confidence: 99%

Cell morphology as a biological fingerprint of chondrocyte phenotype in control and inflammatory conditions

et al. 2023

Self Cite

View full text Add to dashboard Cite

IntroductionLittle is known how inflammatory processes quantitatively affect chondrocyte morphology and how single cell morphometric data could be used as a biological fingerprint of phenotype.MethodsWe investigated whether trainable high-throughput quantitative single cell morphology profiling combined with population-based gene expression analysis can be used to identify biological fingerprints that are discriminatory of control vs. inflammatory phenotypes. The shape of a large number of chondrocytes isolated from bovine healthy and human osteoarthritic (OA) cartilages was quantified under control and inflammatory (IL-1β) conditions using a trainable image analysis technique measuring a panel of cell shape descriptors (area, length, width, circularity, aspect ratio, roundness, solidity). The expression profiles of phenotypically relevant markers were quantified by ddPCR. Statistical analysis, multivariate data exploration, and projection-based modelling were used for identifying specific morphological fingerprints indicative of phenotype.ResultsCell morphology was sensitive to both cell density and IL-1β. In both cell types, all shape descriptors correlated with expression of extracellular matrix (ECM)- and inflammatory-regulating genes. A hierarchical clustered image map revealed that individual samples sometimes responded differently in control or IL-1β conditions than the overall population. Despite these variances, discriminative projection-based modeling revealed distinct morphological fingerprints that discriminated between control and inflammatory chondrocyte phenotypes: the most essential morphological characteristics attributable to non-treated control cells was a higher cell aspect ratio in healthy bovine chondrocytes and roundness in OA human chondrocytes. In contrast, a higher circularity and width in healthy bovine chondrocytes and length and area in OA human chondrocytes indicated an inflammatory (IL-1β) phenotype. When comparing the two species/health conditions, bovine healthy and human OA chondrocytes exhibited comparable IL-1β-induced morphologies in roundness, a widely recognized marker of chondrocyte phenotype, and aspect ratio.DiscussionOverall, cell morphology can be used as a biological fingerprint for describing chondrocyte phenotype. Quantitative single cell morphometry in conjunction with advanced methods for multivariate data analysis allows identifying morphological fingerprints that can discriminate between control and inflammatory chondrocyte phenotypes. This approach could be used to assess how culture conditions, inflammatory mediators, and therapeutic modulators regulate cell phenotype and function.

show abstract

Micro-patterned cell populations as advanced pharmaceutical drugs with precise functional control

Cited by 12 publications

References 269 publications

How Hydrogel Stiffness Affects Adipogenic Differentiation of Mesenchymal Stem Cells under Controlled Morphology

How Hydrogel Stiffness Affects Adipogenic Differentiation of Mesenchymal Stem Cells under Controlled Morphology

Regulation of micropatterned curvature-dependent FA heterogeneity on cytoskeleton tension and nuclear DNA synthesis of malignant breast cancer cells

Cell morphology as a biological fingerprint of chondrocyte phenotype in control and inflammatory conditions

Contact Info

Product

Resources

About