A General Theoretical Framework to Study the Influence of Electrical Fields on Mesenchymal Stem Cells

Jonathan Dawson; Poh Soo Lee; Ursula van Rienen; Revathi Appali

doi:10.3389/fbioe.2020.557447

A General Theoretical Framework to Study the Influence of Electrical Fields on Mesenchymal Stem Cells

Front Bioeng Biotechnol. 2020 Oct 20:8:557447. doi: 10.3389/fbioe.2020.557447. eCollection 2020.

Authors

Jonathan Dawson¹, Poh Soo Lee², Ursula van Rienen^{1

3

4}, Revathi Appali^{1

3}

Affiliations

¹ Department of Computer Science and Electrical Engineering, Institute of General Electrical Engineering, University of Rostock, Rostock, Germany.
² Max Bergmann Center for Biomaterials, Institute for Materials Science, Technical University of Dresden, Dresden, Germany.
³ Department of Ageing of Individuals and Society, Interdisciplinary Faculty, University of Rostock, Rostock, Germany.
⁴ Department of Life, Light and Matter, Interdisciplinary Faculty, University of Rostock, Rostock, Germany.

Abstract

Mesenchymal stem cell dynamics involve cell proliferation and cell differentiation into cells of distinct functional type, such as osteoblasts, adipocytes, or chondrocytes. Electrically active implants influence these dynamics for the regeneration of the cells in damaged tissues. How applied electric field influences processes of individual stem cells is a problem mostly unaddressed. The mathematical approaches to study stem cell dynamics have focused on the stem cell population as a whole, without resolving individual cells and intracellular processes. In this paper, we present a theoretical framework to describe the dynamics of a population of stem cells, taking into account the processes of the individual cells. We study the influence of the applied electric field on the cellular processes. We test our mean-field theory with the experiments from the literature, involving in vitro electrical stimulation of stem cells. We show that a simple model can quantitatively describe the experimentally observed time-course behavior of the total number of cells and the total alkaline phosphate activity in a population of mesenchymal stem cells. Our results show that the stem cell differentiation rate is dependent on the applied electrical field, confirming published experimental findings. Moreover, our analysis supports the cell density-dependent proliferation rate. Since the experimental results are averaged over many cells, our theoretical framework presents a robust and sensitive method for determining the effect of applied electric fields at the scale of the individual cell. These results indicate that the electric field stimulation may be effective in promoting bone regeneration by accelerating osteogenic differentiation.

Keywords: data-driven modeling; electrical stimulation; human mesenchymal cells; mathematical modeling; mean-field approach; stem cell differentiation.