Experimental analysis and modelling of in vitro proliferation of mesenchymal stem cells

Objectives: Stem cell therapies based on differentiation of adult or embryonic stem cells into specialized ones appear to be effective for treating several human diseases. This work addresses the mathematical simulation of proliferation kinetics of stem cells. Materials and methods: Sheep bone marrow mesenchymal stem cells (phenotype characterized by flow cytometry analysis) seeded at different initial concentrations in Petri dishes were expanded to confluence. Sigmoid temporal profiles of total counts obtained through classic haemocytometry were quantitatively interpreted by both a phenomenological logistic equation and a novel model based on a one-dimensional, single-staged population balance approach capable of taking into account contact inhibition at confluence. The models' parameters were determined by comparison with experimental data on population expansion starting from single seeding concentration. Reliability of the models was tested by predicting cell proliferation carried out starting from different seeding concentrations. Results and discussion: It was found that the proposed population balance modelling approach was successful in predicting the experimental data over the whole range of initial cell numbers investigated, while prediction capability of phenomenological logistic equation was more limited.