Cell density overrides the effect of substrate stiffness on human mesenchymal stem cells’ morphology and proliferation

Venugopal, Balaji; Mogha, Pankaj; Dhawan, Jyotsna; Majumder, Abhijit

doi:10.1039/c7bm00853h

Cited by 65 publications

(60 citation statements)

References 37 publications

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“…Spatial distribution of cells in monolayer culture is often observed . The different spatial distribution in culture vessel can affect growth kinetics.…”

Section: Bioprocess Design Considerations To Enhance Scalable Expansimentioning

confidence: 99%

“…The different spatial distribution in culture vessel can affect growth kinetics. Recent experiments on seeding density and seeding uniformity have demonstrated that depending on the distance between the neighboring cells, the mechano‐response of a cell may vary dramatically . At low seeding density, cells are located far from each other and when dividing, each form clonal colonies.…”

Section: Bioprocess Design Considerations To Enhance Scalable Expansimentioning

confidence: 99%

“…[23,24] Spatial distribution of cells in monolayer culture is often observed. [57][58][59][60][61] The different spatial distribution in culture vessel can affect growth kinetics. Recent experiments on seeding density and seeding uniformity have demonstrated that depending on the distance between the neighboring cells, the mechanoresponse of a cell may vary dramatically.…”

Section: Monolayer Culturementioning

confidence: 99%

“…Recent experiments on seeding density and seeding uniformity have demonstrated that depending on the distance between the neighboring cells, the mechanoresponse of a cell may vary dramatically. [60,61] At low seeding density, cells are located far from each other and when dividing, each form clonal colonies. When these colonies reach a larger size, cell growth is inhibited in the center of a colony owing to contact inhibition.…”

Section: Monolayer Culturementioning

confidence: 99%

“…hPSCs spontaneously aggregate and adhere to each other through cell-cell adhesion molecules, such as cadherin, because the cells are not attached to any substrate. [61][62][63][64][65][66] Because the process of aggregate formation of hPSCs in suspension culture depends on expression and affinities of integrins and cadherins, the secretion of ECM protein such as collagen type I by cells may affect survival and growth characteristics. [64] In later phase of culture, the aggregate size shifts and the fraction of larger aggregates increase.…”

Section: Suspension Culturementioning

confidence: 99%

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Bioengineering Considerations for a Nurturing Way to Enhance Scalable Expansion of Human Pluripotent Stem Cells

Kim

Kino‐oka

2020

Biotechnology Journal

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Understanding how defects in mechanotransduction affect cell‐to‐cell variability will add to the fundamental knowledge of human pluripotent stem cell (hPSC) culture, and may suggest new approaches for achieving a robust, reproducible, and scalable process that result in consistent product quality and yields. Here, the current state of the understanding of the fundamental mechanisms that govern the growth kinetics of hPSCs between static and dynamic cultures is reviewed, the factors causing fluctuations are identified, and culture strategies that might eliminate or minimize the occurrence of cell‐to‐cell variability arising from these fluctuations are discussed. The existing challenges in the development of hPSC expansion methods for enabling the transition from process development to large‐scale production are addressed, a mandatory step for industrial and clinical applications of hPSCs.

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“…Spatial distribution of cells in monolayer culture is often observed . The different spatial distribution in culture vessel can affect growth kinetics.…”

Section: Bioprocess Design Considerations To Enhance Scalable Expansimentioning

confidence: 99%

Section: Bioprocess Design Considerations To Enhance Scalable Expansimentioning

confidence: 99%

Section: Monolayer Culturementioning

confidence: 99%

Section: Monolayer Culturementioning

confidence: 99%

Section: Suspension Culturementioning

confidence: 99%

See 3 more Smart Citations

Bioengineering Considerations for a Nurturing Way to Enhance Scalable Expansion of Human Pluripotent Stem Cells

Kim

Kino‐oka

2020

Biotechnology Journal

View full text Add to dashboard Cite

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High‐Throughput Multiparametric Quantification of Mechanics Driven Heterogeneity in Mesenchymal Stromal Cell Population

Kaonis,

Aboellail,

Forman

et al. 2023

Advanced Biology

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Mesenchymal stromal or stem cells (MSCs) are one of the most promising candidates for a myriad of cell therapy applications. Despite showing promise in numerous preclinical and clinical studies, MSC‐based therapy is not yet a reality for regenerative medicine due to its suboptimal outcome at the clinical endpoint. The mechanical environment is a critical determinant of MSC gene expression and function. This study reports that MSC population becomes phenotypically heterogenous and commits to an unwanted osteoprogenitor pathway when it experiences an abnormal mechanically stiff environment, compared to its native softer environment. A method is developed to measure the heterogeneity using nuclear shape, chromatin state, and CD73 marker. Heterogeneity is shown to be associated with a larger spread in the nuclear shape parameters and a smaller spread in the chromatin openness. Subsequently, intervention strategies are investigated to create a more homogeneous MSC population. Culturing MSCs on soft surfaces or inhibiting actomyosin on stiff surfaces can make them more homogeneous, while inhibiting YAP, Runx2, and actin polymerization helps maintain but does not fully homogenize them. This study offers insights for cell and tissue engineers, aiding in the design of optimal conditions and materials for MSC culture, ultimately enhancing their therapeutic potential.

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Hydrogel Alginate Considerations for Improved 3D Matrix Stability and Cell Graft Viability and Function in Studying Type 1 Diabetes In Vitro

Quiroz,

Wang,

Rakoski

et al. 2024

Advanced Biology

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Biomedical devices such as islet‐encapsulating systems are used for treatment of type 1 diabetes (T1D). Despite recent strides in preventing biomaterial fibrosis, challenges remain for biomaterial scaffolds due to limitations on cells contained within. The study demonstrates that proliferation and function of insulinoma (INS‐1) cells as well as pancreatic rat islets may be improved in alginate hydrogels with optimized gel%, crosslinking, and stiffness. Quantitative polymerase chain reaction (qPCR)‐based graft phenotyping of encapsulated INS‐1 cells and pancreatic islets identified a hydrogel stiffness range between 600 and 1000 Pa that improved insulin Ins and Pdx1 gene expression as well as glucose‐sensitive insulin‐secretion. Barium chloride (BaCl2) crosslinking time is also optimized due to toxicity of extended exposure. Despite possible benefits to cell viability, calcium chloride (CaCl2)‐crosslinked hydrogels exhibited a sharp storage modulus loss in vitro. Despite improved stability, BaCl2‐crosslinked hydrogels also exhibited stiffness losses over the same timeframe. It is believed that this is due to ion exchange with other species in culture media, as hydrogels incubated in dIH2O exhibited significantly improved stability. To maintain cell viability and function while increasing 3D matrix stability, a range of useful media:dIH2O dilution ratios for use are identified. Such findings have importance to carry out characterization and optimization of cell microphysiological systems with high fidelity in vitro.

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Cell density overrides the effect of substrate stiffness on human mesenchymal stem cells’ morphology and proliferation

Abstract: Cell–cell interaction via substrate deformation in turn modifies cellular response to substrate rigidity.

Cited by 65 publications

References 37 publications

Bioengineering Considerations for a Nurturing Way to Enhance Scalable Expansion of Human Pluripotent Stem Cells

Bioengineering Considerations for a Nurturing Way to Enhance Scalable Expansion of Human Pluripotent Stem Cells

High‐Throughput Multiparametric Quantification of Mechanics Driven Heterogeneity in Mesenchymal Stromal Cell Population

Hydrogel Alginate Considerations for Improved 3D Matrix Stability and Cell Graft Viability and Function in Studying Type 1 Diabetes In Vitro

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