Please introduce yourself and your home institution.
I am a biomedical engineer and currently a postdoctoral researcher at the J. Crayton Pruitt Family Department of Biomedical Engineering, at the University of Florida (FL, USA).
What is your definition of an MSC? Are they true stem cells?
This is a controversial topic at the moment. However, increasing evidence in vivo support the fact that MSCs are not pluripotent or multipotent. Arnold Caplan, also known as the father of MSCs, recently published a paper in Stem Cells Translational Medicine, entitled “Mesenchymal Stem Cells: Time to Change the Name!”; in the paper, he explained that, “Perhaps we should call them magic signaling cells, more strategic cells, maxi secreting cells, most sensitive cells, main secreting cells, or message secreting cells, but not stem cells!”
I am not a biologist and I am also learning. A couple of years ago I used the same terminology, which was common among the scientists in our field, but now I think it is time to change.
Please give a brief overview of the project on direct current electrical stimulation of mesenchymal stem cells. How did this project come about?
The goal of this project was initially to build an in vitro model for applying electrical stimulation (ES) to the cells. It has been shown that bioelectrical signals play a key role in cellular pathways involved in healing (Levin, 2009). The long-recognized piezoelectric characteristics of bone (electricity resulting from mechanical pressure), together with the known links between ES and bone growth, make bone an attractive target tissue for investigating the role of ES in bone regeneration and healing (Tofail, Zhang & Gandhi, 2011). ES has been successfully used to treat bone defects clinically for more than 40 years (Ryaby, 1998). Nevertheless, the mechanism by which ES promotes bone healing and remodeling is still poorly understood, and the optimal paradigm of such stimulation also hasn’t been studied comprehensively.
In 2014, I moved to the Frankfurt Initiative for Regenerative Medicine (Germany) to work on a project “investigating electrical stimulation of the cells for bone regeneration”. When I joined John Barker’s group, Liudmila Leppik, another postdoc of his group, was working on replication of a famous experiment which was done by Robert Becker 40 years ago. The goal of that study was to see how electrical stimulation affects complex tissue regeneration. I was fascinated and learned a lot from Becker’s model and from the results of our lab on 28-day electrical stimulation of the amputated forelimbs of rats. Our group showed MSCs appeared on the cathode side of the device in the electrically stimulated groups.
Therefore, we thought to make an in vitro model for studying the effect of ES on the cells and, in particular, MSCs. We basically needed an apparatus that applies ES to the cells in culture. Therefore, I built this device and tested the changes in MSCs proliferation and osteogenic differentiation in the presence of DC voltage.
What are the advantages of using direct current electrical stimulation to support the growth of stem cells?
Inducing proliferation or controlling any other cell behavior via ES can help to reduce or even eliminate the use of chemical reagents and drugs for controlling such processes. This is important because of the systemic effects and side effects that drugs could have. In addition, regulatory limitations of using growth factors or biological products from animals for human cell therapy (e.g., serum) limit our choices. Therefore, if we can induce and control proliferation or any particular cellular response using ES, we can scale up a sustainable system for production of the cells and valuable secreted factors from the cells with minimum intermediation of biochemical reagents. This could be interesting for clinical and therapeutic purposes, which need large amounts of the cells/cells’ products, in a limited time.
“Perhaps we should call them magic signaling cells, more strategic cells, maxi secreting cells…but not stem cells!” Arnold Caplan
What are the challenges of using direct current electrical stimulation?
The main challenge for both in vivo and in vitro systems is to find the optimal regime/regimes for each propose. If you look at the literature, the reported ES parameters (such as voltage intensity, signal shape and offset, frequency, and duration) are all over the place. In addition, applying and controlling current versus voltage, and defining the leading mechanisms by which current/voltage trigger responses in cells, are remaining questions. Also, there is a lack of studies on generating a reliable computational model which can calculate or predict cells reaction within the electrical field.
Another challenge for developing in vitro systems is to replicate the in vivo conditions in vitro. Since each tissue type has different conductivity and their endogenous electrical fields are different. Challenges for in vivo systems, however, are more related to finding an effective mitigation strategy for foreign body responses which affect functionality and durability of the electrodes.
Why did you test your system on mesenchymal stem cells?
MSCs are known for their ability to proliferate and differentiate in vitro and their contribution in healing and regeneration in vivo. These cells are involved in numerous clinically approved trials of cell therapy procedures. Therefore, to understand ES mechanisms associated with these cells has translational and clinical benefits.
What advancements have you made in this project since your paper was published?
I joined Sarah Cartmell’s group at the University of Manchester (UK). By that time, she had published a paper entitled “Electrical Stimulation as a Tool for Tissue Engineering”, which I cited frequently, and I was excited to work with the author of that paper. We worked on the idea of electrobioreactor with perfusion system. I learned a lot and had a chance to run computational modeling of my device. We published a paper together about changes in the cell cytoskeleton within the electrical field.
Subsequently, I was recruited by Christine E. Schmidt, University of Florida, who is a pioneer in developing different strategies for neural tissue engineering. I improved the design of the device in her lab and tried different regimes of ES on different cell types, such as Schwann cells and cardiomyocytes.
What more do you hope to achieve?
I believe electrical field is a unique way that cells are communicating to each other and with the outside. If we learn their language, we can communicate with them. I am continuing studies on ES of the cells for neural tissue plasticity both as in vitro models and therapeutics.