ArticleBMC systems biology2018
Mathematical modelling of interacting mechanisms for hypoxia mediated cell cycle commitment for mesenchymal stromal cells.
Article in BMC systems biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed, 9 citations in OpenAlex.
- A dynamic model of gene activation in response to hypoxia accounting for both HIF-1 and HIF-2.Briefings in functional genomics · 2025Article
- Differential Oxygen Exposure Modulates Mesenchymal Stem Cell Metabolism and Proliferation through mTOR Signaling.International journal of molecular sciences · 2022Article
- In silico simulation of the effect of hypoxia on MCF-7 cell cycle kinetics under fractionated radiotherapy.Journal of biological physics · 2021Article
- Interleukin-15 Signaling in HIF-1α Regulation in Natural Killer Cells, Insights Through Mathematical Models.Frontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundExisting experimental data have shown hypoxia to be an important factor affecting the proliferation of mesenchymal stromal cells (MSCs), but the contrasting observations made at various hypoxic levels raise the questions of whether hypoxia accelerates proliferation, and how. On the other hand, in order to meet the increasing demand of MSCs, an optimised bioreactor control strategy is needed to enhance in vitro production.
resultsA comprehensive, single-cell mathematical model has been constructed in this work, which combines cellular oxygen sensing with hypoxia-mediated cell cycle progression to predict cell cycle commitment as a proxy to proliferation rate. With oxygen levels defined for in vitro cell culture, the model predicts enhanced proliferation under intermediate (2-8%) and mild (8-15%) hypoxia and cell quiescence under severe (< 2%) hypoxia. Global sensitivity analysis and quasi-Monte Carlo simulation revealed that within a certain range (+/- 100%), model parameters affect (with varying significance) the minimum commitment time, but the existence of a range of optimal oxygen tension could be preserved with the hypothesized effects of Hif2α and reactive oxygen species (ROS). It appears that Hif2α counteracts Hif1α and ROS-mediated protein deactivation under intermediate hypoxia and normoxia (20%), respectively, to regulate the response of cell cycle commitment to oxygen tension.
conclusionOverall, this modelling study offered an integrative framework to capture several interacting mechanisms and allowed in silico analysis of their individual and collective roles in shaping the hypoxia-mediated commitment to cell cycle. The model offers a starting point to the establishment of a suitable mechanism that can satisfactorily explain the different existing experimental observations from different studies, and warrants future extension and dedicated experimental validation to eventually support bioreactor optimisation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.