scholarly journals The Mechanical Interplay Between Differentiating Mesenchymal Stem Cells and Gelatin-Based Substrates Measured by Atomic Force Microscopy

2021 ◽  
Vol 9 ◽  
Author(s):  
Hongxu Meng ◽  
Tina T. Chowdhury ◽  
Núria Gavara
Keyword(s):  
Mechanical Properties ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Stem Cell Differentiation ◽  
Multiple Time ◽  
Time Points ◽  
Surrounding Matrix ◽  
Multiple Time Points ◽  
Highly Correlated

Traditional methods to assess hMSCs differentiation typically require long-term culture until cells show marked expression of histological markers such as lipid accumulation inside the cytoplasm or mineral deposition onto the surrounding matrix. In parallel, stem cell differentiation has been shown to involve the reorganization of the cell’s cytoskeleton shortly after differentiation induced by soluble factors. Given the cytoskeleton’s role in determining the mechanical properties of adherent cells, the mechanical characterization of stem cells could thus be a potential tool to assess cellular commitment at much earlier time points. In this study, we measured the mechanical properties of hMSCs cultured on soft gelatin-based hydrogels at multiple time points after differentiation induction toward adipogenic or osteogenic lineages. Our results show that the mechanical properties of cells (stiffness and viscosity) and the organization of the actin cytoskeleton are highly correlated with lineage commitment. Most importantly, we also found that the mechanical properties and the topography of the gelatin substrate in the vicinity of the cells are also altered as differentiation progresses toward the osteogenic lineage, but not on the adipogenic case. Together, these results confirm the biophysical changes associated with stem cell differentiation and suggest a mechanical interplay between the differentiating stem cells and their surrounding extracellular matrix.

Guiding Stem Cell Differentiation Into Neural Lineages With Tunable Collagen Biomaterials

2009 ◽  
Author(s):  
Gary A. Monteiro ◽  
David I. Shreiber
Keyword(s):  
Mechanical Properties ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Type I Collagen ◽  
Striated Muscle ◽  
Stem Cell Differentiation ◽  
Type I ◽  
Collagen Gels ◽  
Biomaterial Scaffolds

The long-term objective of this research is to develop tunable collagen-based biomaterial scaffolds for directed stem cell differentiation into neural lineages to aid in CNS diseases and trauma. Type I collagen is a ubiquitous protein that provides mechanostructural and ligand-induced biochemical cues to cells that attach to the protein via integrin receptors. Previous studies have demonstrated that the mechanical properties of a substrate or tissue can be an important regulator of stem cell differentiation. For example, the mechanical properties polyacrylamide gels can be tuned to induce neural differentiation from stem cells [1, 2]. Mesenchymal stem cells (MSCs) cultured on ployacrylamide gels with low elastic modulus (0.1–1 kPa) resulted in a neural like population. MSCs on 10-fold stiffer matrices that mimic striated muscle elasticity (Emuscle ∼8–17 kPa) lead to spindle-shaped cells similar in shape to myoblasts. Still stiffer gels (25–40 kPa) resulted in osetoblast differentiation. Based on these observations, collagen gels may provide an ideal material for differentiation into neural lineages because of their low compliance.

AFM Assessment of the Mechanical Properties of Stem Cells During Differentiation

MRS Advances ◽  
2019 ◽  
Vol 5 (12-13) ◽  
pp. 601-607
Author(s):  
Jie Zou ◽  
Weiwei Wang ◽  
Xianlei Sun ◽  
Wingtai Tung ◽  
Nan Ma ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Stem Cells ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Cell Fate ◽  
Stem Cell Differentiation ◽  
Cell Nuclei ◽  
Gene And Protein Expression ◽  
Marrow Mesenchymal Stem Cells

ABSTRACTThe dynamic mechanical force transmitted through microenvironments during tissue formation and regeneration continuously impacts the mechanics of cells and thereby regulates gene and protein expression. The mechanical properties are altered during the process of stem cells differentiating into different lineages. At different stages of differentiation, stem cells display different mechanical properties in response to surrounding microenvironments, which depend on the subcellular structures, especially the cytoskeleton and nucleus. The mechanical properties of the cell nucleus affect protein folding and transport as well as the condensation of chromatin, through which the cell fate is regulated. These findings raise the question as to how cell mechanics change during differentiation. In this study, the mechanical properties of human bone marrow mesenchymal stem cells (hBMSCs) were determined during adipogenic and osteogenic differentiation by atomic force microscopy (AFM). The cytoskeletal structure and the modification of histone were investigated using laser confocal microscope and flow cytometry. The mechanical properties of cell nuclei at different stages of cell differentiation were compared. The stiffness of nuclei increased with time as osteogenesis was induced in hBMSCs. The H3K27me3 level increased during osteogenesis and adipogenesis according to flow cytometry analysis. Our results show conclusively that AFM is a facile and effective method to monitor stem cell differentiation. The measurement of cell mechanical properties by AFM improves our understanding on the connection between mechanics and stem cell fate.

scholarly journals DYRK1A Negatively Regulates CDK5-SOX2 Pathway and Self-Renewal of Glioblastoma Stem Cells

2021 ◽  
Vol 22 (8) ◽  
pp. 4011
Author(s):  
Brianna Chen ◽  
Dylan McCuaig-Walton ◽  
Sean Tan ◽  
Andrew P. Montgomery ◽  
Bryan W. Day ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Critical Role ◽  
Stem Cell Differentiation ◽  
Neural Progenitor Cell ◽  
Cellular Heterogeneity ◽  
Differentiation Potential ◽  
Glioblastoma Stem Cells ◽  
Glioblastoma Stem Cell

Glioblastoma display vast cellular heterogeneity, with glioblastoma stem cells (GSCs) at the apex. The critical role of GSCs in tumour growth and resistance to therapy highlights the need to delineate mechanisms that control stemness and differentiation potential of GSC. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) regulates neural progenitor cell differentiation, but its role in cancer stem cell differentiation is largely unknown. Herein, we demonstrate that DYRK1A kinase is crucial for the differentiation commitment of glioblastoma stem cells. DYRK1A inhibition insulates the self-renewing population of GSCs from potent differentiation-inducing signals. Mechanistically, we show that DYRK1A promotes differentiation and limits stemness acquisition via deactivation of CDK5, an unconventional kinase recently described as an oncogene. DYRK1A-dependent inactivation of CDK5 results in decreased expression of the stemness gene SOX2 and promotes the commitment of GSC to differentiate. Our investigations of the novel DYRK1A-CDK5-SOX2 pathway provide further insights into the mechanisms underlying glioblastoma stem cell maintenance.

scholarly journals Identification of cardiac stem cells with FLK1, CD31, and VE‐cadherin expression during embryonic stem cell differentiation

2005 ◽  
Vol 19 (3) ◽  
pp. 371-378 ◽  
Author(s):  
Midori Iida ◽  
Toshio Heike ◽  
Momoko Yoshimoto ◽  
Shiro Baba ◽  
Hiraku Doi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
Cardiac Stem Cells

scholarly journals Nuclear Export of Smads by RanBP3L Regulates Bone Morphogenetic Protein Signaling and Mesenchymal Stem Cell Differentiation

2015 ◽  
Vol 35 (10) ◽  
pp. 1700-1711 ◽  
Author(s):  
Fenfang Chen ◽  
Xia Lin ◽  
Pinglong Xu ◽  
Zhengmao Zhang ◽  
Yanzhen Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Mesenchymal Stem Cell ◽  
Nuclear Export ◽  
Stem Cell Differentiation ◽  
Bmp Signaling ◽  
Dependent Manner ◽  
Mesenchymal Stem Cell Differentiation

Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance and differentiation. BMPs can induce osteogenesis and inhibit myogenesis of mesenchymal stem cells. Canonical BMP signaling is stringently controlled through reversible phosphorylation and nucleocytoplasmic shuttling of Smad1, Smad5, and Smad8 (Smad1/5/8). However, how the nuclear export of Smad1/5/8 is regulated remains unclear. Here we report that the Ran-binding protein RanBP3L acts as a nuclear export factor for Smad1/5/8. RanBP3L directly recognizes dephosphorylated Smad1/5/8 and mediates their nuclear export in a Ran-dependent manner. Increased expression of RanBP3L blocks BMP-induced osteogenesis of mouse bone marrow-derived mesenchymal stem cells and promotes myogenic induction of C2C12 mouse myoblasts, whereas depletion of RanBP3L expression enhances BMP-dependent stem cell differentiation activity and transcriptional responses. In conclusion, our results demonstrate that RanBP3L, as a nuclear exporter for BMP-specific Smads, plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation.

Magnetic field assisted stem cell differentiation – role of substrate magnetization in osteogenesis

2015 ◽  
Vol 3 (16) ◽  
pp. 3150-3168 ◽  
Author(s):  
Sunil Kumar Boda ◽  
Greeshma Thrivikraman ◽  
Bikramjit Basu
Keyword(s):  
Magnetic Field ◽  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Bone Tissue Engineering ◽  
Human Mesenchymal Stem Cells ◽  
Stem Cell Differentiation

Substrate magnetization as a tool for modulating the osteogenesis of human mesenchymal stem cells for bone tissue engineering applications.

scholarly journals Induction of Cancerous Stem Cells during Embryonic Stem Cell Differentiation

2012 ◽  
Vol 287 (44) ◽  
pp. 36777-36791 ◽  
Author(s):  
Hiroaki Fujimori ◽  
Mima Shikanai ◽  
Hirobumi Teraoka ◽  
Mitsuko Masutani ◽  
Ken-ichi Yoshioka
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation

scholarly journals Mechanical Properties of Materials for Stem Cell Differentiation

2020 ◽  
Vol 4 (11) ◽  
pp. 2000247
Author(s):  
Seong‐Beom Han ◽  
Jeong‐Ki Kim ◽  
Geonhui Lee ◽  
Dong‐Hwee Kim
Keyword(s):  
Mechanical Properties ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Stem Cell Differentiation ◽  
Mechanical Properties Of Materials ◽  
Properties Of Materials

scholarly journals Developmental Pathways Pervade Stem Cell Responses to Evolving Extracellular Matrices of 3D Bioprinted Microenvironments

2018 ◽  
Vol 2018 ◽  
pp. 1-15
Author(s):  
Quyen A. Tran ◽  
Visar Ajeti ◽  
Brian T. Freeman ◽  
Paul J. Campagnola ◽  
Brenda M. Ogle
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Early Time ◽  
Stem Cell Differentiation ◽  
Model Systems ◽  
Ecm Remodeling ◽  
Time Points ◽  
3D Microenvironment

Developmental studies and 3D in vitro model systems show that the production and engagement of extracellular matrix (ECM) often precede stem cell differentiation. Yet, unclear is how the ECM triggers signaling events in sequence to accommodate multistep process characteristic of differentiation. Here, we employ transcriptome profiling and advanced imaging to delineate the specificity of ECM engagement to particular differentiation pathways and to determine whether specificity in this context is a function of long-term ECM remodeling. To this end, human mesenchymal stem cells (hMSCs) were cultured in 3D bioprinted prisms created from ECM proteins and associated controls. We found that exogenous ECM provided in 3D microenvironments at early time points impacts on the composition of microenvironments at later time points and that each evolving 3D microenvironment is uniquely poised to promote stem cell differentiation. Moreover, 2D cultures undergo minimal ECM remodeling and are ill-equipped to stimulate pathways associated with development.

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