Anoxia resistance of cultured multipotent mesenchymal stromal cells from adipose tissue

Rylova, J. V.; Буравкова, Л. Б.

doi:10.1134/s1990519x1502008x

Cited by 1 publication

(1 citation statement)

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“…Several assumptions and simplifications were made to allow the construction of the current model, which require caution in interpreting the simulation results and, in many cases, point to important future work: The model focuses on the overall oxygen-dependent behaviour of cell cycle commitment and is not expected to be taken for making predictions at rather extreme conditions. In particular, under severe hypoxia pro-survival response in stem cells is expected to dominate and could result in quiescence to reduce DNA damage [ 9 , 21 , 88 ] despite a few reports showed the successful proliferation of MSCs under anoxic conditions [ 89 , 90 ], which may be due to different factors as addressed in the original papers. The current model only estimates the time required for commitment to cell cycle in late-G1 phase.…”

Section: Discussionmentioning

confidence: 99%

Mathematical modelling of interacting mechanisms for hypoxia mediated cell cycle commitment for mesenchymal stromal cells

Zhang

Yang

2018

BMC Syst Biol

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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.Electronic supplementary materialThe online version of this article (10.1186/s12918-018-0560-3) contains supplementary material, which is available to authorized users.

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