Stochastic cellular automata model of neurosphere growth: Roles of proliferative potential, contact inhibition, cell death, and phagocytosis

Journal of Theoretical Biology
Rifat Sipahi, Günther K H Zupanc

Abstract

Neural stem and progenitor cells isolated from the central nervous system form, under specific culture conditions, clonal cell clusters known as neurospheres. The neurosphere assay has proven to be a powerful in vitro system to study the behavior of such cells and the development of their progeny. However, the theory of neurosphere growth has remained poorly understood. To overcome this limitation, we have, in the present paper, developed a cellular automata model, with which we examined the effects of proliferative potential, contact inhibition, cell death, and clearance of dead cells on growth rate, final size, and composition of neurospheres. Simulations based on this model indicated that the proliferative potential of the founder cell and its progenitors has a major influence on neurosphere size. On the other hand, contact inhibition of proliferation limits the final size, and reduces the growth rate, of neurospheres. The effect of this inhibition is particularly dramatic when a stem cell becomes encapsulated by differentiated or other non-proliferating cells, thereby suppressing any further mitotic division - despite the existing proliferative potential of the stem cell. Conversely, clearance of dead cells through phagocyt...Continue Reading

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Citations

Mar 5, 2019·Developmental Neurobiology·Günther K H Zupanc
May 19, 2019·Developmental Neurobiology·Dávid Lehotzky, Günther K H Zupanc
Dec 22, 2020·PloS One·Priyom AdhyapokJames A Glazier
Feb 2, 2019·Journal of Theoretical Biology·Günther K H ZupancRifat Sipahi
Mar 26, 2021·Molecular Biology Reports·Laura da Silva SiqueiraDaniel Rodrigo Marinowic
Aug 27, 2021·Membranes·Priscila Elias Ferreira StrickerKatherine Athayde Teixeira de Carvalho

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