RT info:eu-repo/semantics/article
T1 An in-silico approach to the dynamics of proliferation potential in stem cells and the study of different therapies in cases of ovarian dysfunction
A1 Portillo, Ana M
K1 Differential equation Aging Telomere length Telomerase activity Stem cells
K1 62P10 65L05 65M22
AB A discrete mathematical model based on ordinary differential equations and the associatedcontinuous model formed by a partial differential equation, which simulate the generationaland temporal evolution of a stem cell population, are proposed. The model parameters are themaximum proliferation potential and the rates of mitosis, death events and telomerase activity.The mean proliferation potential at each point in time is suggested as an indicator of populationageing. The model is applied on hematopoietic stem cells (HSCs), with different telomeraseactivity rates, in a range of variation of maximum proliferation potential in healthy individuals,to study the temporal evolution of ageing. HSCs express telomerase, however not at levels that aresufficient for maintaining constant telomere length with aging (Zimmermann and Martens, 2008;Flores et al., 2008). Women with primary ovarian insufficiency (POI) are known to have lowtelomerase activity in granulosa cells and peripheral blood mononuclear cells (Xu et al., 2017).Extrapolating this to haematopoietic stem cells, the mathematical model shows the differencesin proliferation potential of the cell populations when telomerase expression is activated usingsexual steroids, though the endogenous promoter or with gene therapy using exogenous, strongerpromoters within the adeno-associated virus. In the first case, proliferation potential of cells fromPOI condition increases, but when adeno-associated viruses are used, the proliferation potentialreaches the levels of healthy cell populations.
YR 2024
FD 2024-11
LK https://uvadoc.uva.es/handle/10324/70503
UL https://uvadoc.uva.es/handle/10324/70503
LA eng
NO Mathematical Biosciences, Volume 377, November 2024,  109305, ISSN 0025-5564
DS UVaDOC
RD 22-dic-2024