Role of Bioelectricity During Cell Proliferation in Different Cell Types.

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.

Electrical stimulation-based bone fracture treatment, if it works so well why do not more surgeons use it?

BACKGROUND: Electrical stimulation (EStim) has been proven to promote bone healing in experimental settings and has been used clinically for many years and yet it has not become a mainstream clinical treatment. METHODS: To better understand this discrepancy we reviewed 72 animal and 69 clinical studies published between 1978 and 2017, and separately asked 161 orthopedic surgeons worldwide about their awareness, experience, and acceptance of EStim for treating fracture patients. RESULTS: Of the 72 animal studies, 77% reported positive outcomes, and the most common model, bone, fracture type, and method of administering EStim were dog, tibia, large bone defects, and DC, respectively. Of the 69 clinical studies, 73% reported positive outcomes, and the most common bone treated, fracture type, and method of administration were tibia, delayed/non-unions, and PEMF, respectively. Of the 161 survey respondents, most (73%) were aware of the positive outcomes reported in the literature, yet only 32% used EStim in their patients. The most common fracture they treated was delayed/non-unions, and the greatest problems with EStim were high costs and inconsistent results. CONCLUSION: Despite their awareness of EStim's pro-fracture healing effects few orthopedic surgeons use it in their patients. Our review of the literature and survey indicate that this is due to confusion in the literature due to the great variation in methods reported, and the inconsistent results associated with this treatment approach. In spite of this surgeons seem to be open to using this treatment if advancements in the technology were able to provide an easy to use, cost-effective method to deliver EStim in their fracture patients.

Membrane potential (Vmem) measurements during mesenchymal stem cell (MSC) proliferation and osteogenic differentiation.

BACKGROUND: Electrochemical signals play an important role in cell communication and behavior. Electrically charged ions transported across cell membranes maintain an electrochemical imbalance that gives rise to bioelectric signaling, called membrane potential or Vmem. Vmem plays a key role in numerous inter- and intracellular functions that regulate cell behaviors like proliferation, differentiation and migration, all playing a critical role in embryonic development, healing, and regeneration. METHODS: With the goal of analyzing the changes in Vmem during cell proliferation and differentiation, here we used direct current electrical stimulation (EStim) to promote cell proliferation and differentiation and simultaneously tracked the corresponding changes in Vmem in adipose derived mesenchymal stem cells (AT-MSC). RESULTS: We found that EStim caused increased AT-MSC proliferation that corresponded to Vmem depolarization and increased osteogenic differentiation that corresponded to Vmem hyperpolarization. Taken together, this shows that Vmem changes associated with EStim induced cell proliferation and differentiation can be accurately tracked during these important cell functions. Using this tool to monitor Vmem changes associated with these important cell behaviors we hope to learn more about how these electrochemical cues regulate cell function with the ultimate goal of developing new EStim based treatments capable of controlling healing and regeneration.