ArticleStem cells international2018
Mathematical Modeling Reveals the Role of Hypoxia in the Promotion of Human Mesenchymal Stem Cell Long-Term Expansion.
Article in Stem cells international, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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Who cites it
5 citing papers in PubMed.
- Cell-based therapeutic strategies for treatment of spinocerebellar ataxias: an update.Neural regeneration research · 2023Review
- Merits and Demerits of ODE Modeling of Physicochemical Systems for Numerical Simulations.Molecules (Basel, Switzerland) · 2022Review
- Senescent mesenchymal stem/stromal cells and restoring their cellular functions.World journal of stem cells · 2020Review
- Mesenchymal stem cells cultured under hypoxic conditions had a greater therapeutic effect on mice with liver cirrhosis compared to those cultured under normal oxygen conditions.Regenerative therapy · 2019Article
- Improved Isolation of Mesenchymal Stem Cells Based on Interactions betweenStem cells international · 2019Article
Corrections and comments
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Authors and funding
4 authors.
Funding
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Abstract
Many experimental studies have found that human mesenchymal stem cells (MSCs) in long-term culture exhibited enhanced cell proliferation and prolonged lifespan under hypoxia (around 1%-7% oxygen) against the normoxic condition (about 21% oxygen). Inspired by the experimental findings, we aimed to investigate the hypoxic effects on MSC expansion quantitatively through mathematical modeling to elucidate the corresponding biological mechanism. A two-compartment model based on ordinary differential equations (ODEs), which incorporate cellular division and senescence via state transition, was developed to describe the MSC expansion process. Parameters of this model were fitted to experimental data and used to interpret the different proliferative capacities of MSCs under hypoxia and normoxia along with model sensitivity analysis. The proposed model was tested on data from two separate experimental studies, and it could reproduce the observed growth characteristics in both conditions. Overall, this compartmental model with a logistic state transition rate was sufficient to explain the experimental findings and highlighted the promotive role of hypoxia in MSC proliferation. This in silico study suggests that hypoxia can enhance MSC long-term expansion mainly by delaying replicative senescence, which is indicated by the slowdown of the state transition rate in our model. Therefore, this explanatory model may provide theoretical proof for the experimentally observed MSC growth superiority under hypoxia and has the potential to further optimize MSC culture protocols for regenerative medicine applications.
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Registered trials
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