Driving mesenchymal stem cell differentiation from self-assembled monolayers

Tew, Lih Shin; Ching, J. Y.; Ngalim, Siti Hawa; Khung, Yit Lung

doi:10.1039/c7ra12234a

Cited by 16 publications

(14 citation statements)

References 142 publications

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“…Another layer of complexity in the MSCs differentiation comes from the chemical composition of the substrate surface. On the ''soft'' substrates, the chemistry of the groups on polymer surface presented to the adhering MSCs is usually complex and highly heterogeneous, 32 that makes an analysis of the correlation between surface chemistry and cell differentiation in gels uncertain. However, different types of coating of smooth, stiff surfaces with organized self-assembled monolayers (SAMs) carrying on different functional groups can modulate the MSCs' fate.…”

Section: Matrix Properties Regulate Msc Behaviormentioning

confidence: 99%

“…However, different types of coating of smooth, stiff surfaces with organized self-assembled monolayers (SAMs) carrying on different functional groups can modulate the MSCs' fate. 32,33 Methyl group (CH 3 ) stimulates undifferentiated state, amine group (NH 2 ), carboxyl group, (COOH), and phosphate group (PO 3 ) stimulate osteogenic differentiation, while hydroxyl group, (OH) and sometime carboxyl group, stimulates chondrogenic differentiation. [34][35][36][37] Thus, small differences in cell-substrate adhesion are critical for differentiation pattern of MSCs, and new synthetic substrates show perspective to understand this process.…”

Section: Matrix Properties Regulate Msc Behaviormentioning

confidence: 99%

“…83 On the contrary, the overexpression of a v b 3 integrin has an inhibitory effect on prodifferentiation signals triggered by a 5 b 1 integrin, resulting in the absence of osteogenic differentiation. 32 High level of expression of a5 integrin inhibits adipogenic differentiation as well as chondrogenic differentiation. 80 Adipogenic and chondrogenic lineages correlate with downregulation of integrin a5 80,84 in contrast to a6 integrin.…”

Section: Focal Adhesionsmentioning

confidence: 99%

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Lineage Commitment, Signaling Pathways, and the Cytoskeleton Systems in Mesenchymal Stem Cells

Saidova

Vorobjev

2020

Tissue Engineering Part B: Reviews

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Mesenchymal stem cells (MSCs) from adult tissues are promising candidates for personalized cell therapy and tissue engineering. Significant progress was achieved in our understanding of the regulation of MSCs proliferation and differentiation by different cues during the past years. Proliferation and differentiation of MSCs are sensitive to the extracellular matrix (ECM) properties, physical cues, and chemical signaling. Sheath stress, matrix stiffness, surface adhesiveness, and micro-and nanotopography define cell shape and dictate lineage commitment of MSCs even in the absence of specific chemical signals. We discuss mechanotransduction as the major route from ECM through the cytoskeleton toward signaling pathways and gene expression. All components of the cytoskeleton from primary cilium and focal adhesions (FAs) to actin, microtubules (MTs), and intermediate filaments (IFs) are involved in the mechanotransduction. Differentiation of MSCs is regulated via the complex network of interrelated signaling pathways, including RhoA/ROCK, Akt/Erk, and YAP/TAZ effectors of Hippo pathway. These pathways could be regulated both by chemical and mechanical stimuli. Attenuation of these pathways in MSCs results in specific changes in FAs and actin cytoskeleton. Besides, differentiation of MSCs affects MTs and IFs. Recent findings highlight the role of intranuclear actin in the regulation of transcription factors in response to mechanical environmental stimuli. Alterations of cytoskeletal components reflect the MSC senescence state and their migratory capacity. In this review, we discuss the relationships between the molecular interactions in signaling pathways and morphological response of cytoskeletal components and reveal the complex interrelations between cytoskeleton systems and signaling pathways during lineage commitment of MSCs.

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Section: Matrix Properties Regulate Msc Behaviormentioning

confidence: 99%

Section: Matrix Properties Regulate Msc Behaviormentioning

confidence: 99%

Section: Focal Adhesionsmentioning

confidence: 99%

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Lineage Commitment, Signaling Pathways, and the Cytoskeleton Systems in Mesenchymal Stem Cells

Saidova

Vorobjev

2020

Tissue Engineering Part B: Reviews

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“…Care must be taken in modifying substrate properties—while improved fibroblast spreading is correlated with improved attachment, it may also be indicative of a more myofibroblastic, chondrogenic, or osteoblastic character 44 , 46 . However, this concern can be addressed by supplementing FGF2 exogenously, or releasing it over time when culturing cells on a PEM.…”

Section: Resultsmentioning

confidence: 99%

Half-life modeling of basic fibroblast growth factor released from growth factor-eluting polyelectrolyte multilayers

Ding

Peterson

2021

Sci Rep

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Growth factor-eluting polymer systems have been widely reported to improve cell and tissue outcomes; however, measurements of actual growth factor concentration in cell culture conditions are limited. The problem is compounded by a lack of knowledge of growth factor half-lives, which impedes efforts to determine real-time growth factor concentrations. In this work, the half-life of basic fibroblast growth factor (FGF2) was determined using enzyme linked immunosorbent assay (ELISA). FGF2 release from polyelectrolyte multilayers (PEMs) was measured and the data was fit to a simple degradation model, allowing for the determination of FGF2 concentrations between 2 and 4 days of culture time. After the first hour, the FGF2 concentration for PEMs assembled at pH = 4 ranged from 2.67 ng/mL to 5.76 ng/mL, while for PEMs assembled at pH = 5, the concentration ranged from 0.62 ng/mL to 2.12 ng/mL. CRL-2352 fibroblasts were cultured on PEMs assembled at pH = 4 and pH = 5. After 2 days, the FGF2-eluting PEM conditions showed improved cell count and spreading. After 4 days, only the pH = 4 assembly condition had higher cells counts, while the PEM assembled at pH = 5 and PEM with no FGF2 showed increased spreading. Overall, the half-life model and cell culture study provide optimal concentration ranges for fibroblast proliferation and a framework for understanding how temporal FGF2 concentration may affect other cell types.

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“…Care must be taken in modifying substrate propertieswhile improved fibroblast spreading is correlated with improved attachment, it may also be indicative of a more myofibroblastic, chondrogenic, or osteoblastic character. 39,41 However, this concern can be addressed by supplementing FGF2 exogenously, or releasing it over time when culturing cells on a PEM. FGF2…”

Section: Cell Culturementioning

confidence: 99%

Half-Life Modeling of Basic Fibroblast Growth Factor and its Media Concentration from Growth Factor-Eluting Polyelectrolyte Multilayers

Ding

Peterson

2020

Preprint

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Growth factor-eluting polymer systems have been widely reported to improve cell and tissue outcomes; however, measurements of actual growth factor concentration in cell culture conditions are limited. The problem is compounded by a lack of knowledge of growth factor half-lives, which impedes efforts to determine real-time growth factor concentrations. In this work, the half-life of basic fibroblast growth factor (FGF2) was determined using enzyme linked immunosorbent assay (ELISA). FGF2 release from polyelectrolyte multilayers (PEMs) was measured and the data was fit to a simple degradation model, allowing for the determination of FGF2 concentrations between 2 days and 4 days of culture time. After the first hour, the FGF2 concentration for PEMs assembled at pH=4 ranged from 2.67 ng/mL to 5.76 ng/mL, while for PEMs assembled at pH=5, the concentration ranged from 0.62 ng/mL to 2.12 ng/mL. CRL-2352 fibroblasts were cultured on PEMs assembled at pH=4 and pH=5. After 2 days, the FGF2-eluting PEM conditions showed improved cell count and spreading. After 4 days, only the pH=4 assembly condition had higher cells counts, while the PEM assembled at pH=5 and PEM with no FGF2 showed increased spreading. Overall, the half-life model and cell culture study provide optimal concentration ranges for fibroblast proliferation and a framework for understanding how temporal FGF2 concentration may affect other cell types.

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Driving mesenchymal stem cell differentiation from self-assembled monolayers

Abstract: Graphical illustration showing the functional groups that drive MSC differentiation without soluble bioactive cues within the first 14 days.

Cited by 16 publications

References 142 publications

Lineage Commitment, Signaling Pathways, and the Cytoskeleton Systems in Mesenchymal Stem Cells

Lineage Commitment, Signaling Pathways, and the Cytoskeleton Systems in Mesenchymal Stem Cells

Half-life modeling of basic fibroblast growth factor released from growth factor-eluting polyelectrolyte multilayers

Half-Life Modeling of Basic Fibroblast Growth Factor and its Media Concentration from Growth Factor-Eluting Polyelectrolyte Multilayers

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