Abstract

Most living organisms possess varying degrees of regenerative capabilities but how these regenerative processes are controlled is still poorly understood. Naturally occurring bioelectric voltages (like Vmem) are thought to be playing instructive role in tissue regeneration, as well as embryonic development. The different distribution of ions on the either side of the cell membrane results in intra- and extra-cellular voltage differences, known as membrane potential or Vmem. The relationship between Vmem and cell physiology is conserved in a wide range of cell types and suggests that Vmem regulation is a fundamental control mechanism for regeneration related processes e.g., proliferation and differentiation. In the present study we measured Vmem in three different cell types (human osteogenic sarcoma cell line (OSC), rat bone marrow derived mesenchymal stem cells (BM-MSC), and rat dermal fibroblasts) and characterized the relationship between their Vmem and proliferation. In order to find out if Vmem controls proliferation, or visa-versa, we blocked and then unblocked Na+/K+-exchanging ATPase using ouabain and measured the proliferation. Our results demonstrate that Vmem can be pharmacologically manipulated to control proliferation in certain cell types like BM-MSC. Taken together, it is clear that control of bioelectrical properties in non-excitable cells could prove to be potentially a useful tool in regenerative medicine efforts.

Highlights

  • Current reconstructive treatments aimed at restoring normal form and function to diseased, injured or missing tissues and/or organs use a patient’s own tissues, tissues and organs transplanted from donors, or prosthetic devices

  • Vmem values of BM-MSC increased from day 0 to day 10, significant at day 3 and 10 (p < 0.05)

  • We observed that changes in Vmem and proliferation coincided, and that by blocking and unblocking Na+/K+-exchanging ATPase we were able to control proliferation in BM-MSC

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Summary

Introduction

Current reconstructive treatments aimed at restoring normal form and function to diseased, injured or missing tissues and/or organs use a patient’s own tissues, tissues and organs transplanted from donors, or prosthetic devices. While these treatments enjoy varying degrees of success, they are often associated with drawbacks such as limited donor availability, infection, immunological rejection, and high costs (Mao and Mooney, 2015). Regenerative therapies could potentially restore normal tissue form and function, without these drawbacks (Levin and Stevenson, 2012; Bessonov et al, 2015; Tyler, 2017).

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