There is a need for novel clinical strategies to stimulate tissue regeneration after injury. Naturally occurring electric fields (EF) at injuries may promote wound healing and preliminary clinical studies have shown that electrical stimulation using acupuncture needles promoted tissue repair in tendon, muscle and joint related injuries in elite athletes. We tested the hypothesis that EF stimulation of synovial mesenchymal stem cells (SMSCs) can induce tissue repair by promoting cell migration and mitosis. SMSCs isolated from whole C57BC6 mouse knee joints were seeded in Ibidi μ-Slide I channels and an EF of 150 mV/mm was applied for 12 hours. Images were captured at 10-minute intervals for 10 visual fields and time-lapse videos were analysed with ImageJ (v. 1.47). Parameters quantified included the direction (Forward Migration Index; FMIx) and speed of cell migration, and the polarity of cell division. An FMIx value of 0 represents random migration, 1 is anodal migration and -1 is cathodal migration. The axis of cell division was scored between 0 degrees (parallel to EF) to 90 degrees (orthogonal to EF), so randomly directed division yields a mean angle of 45 degrees. Data are reported as mean ± standard error of mean (SEM) and compared with an unpaired 2-tailed Student’s t test. More unsorted (passages P4-P6) synovial cells migrated (44% of n=837; p<0.001) during EF exposure than controls (10% of n=898). Similarly, sorted SMSCs from later passages (P13-P15) migrated more frequently during EF stimulation (28% of n=1465; p<0.001) than controls (8% of n=1546). EF stimulation reduced the migration speed of unsorted (control 12 ± 0.67 µm/h; EF 8.4 ± 0.23 µm/h; p<0.01) but not sorted SMSCs (control 7.5 ± 0.25 µm/h; EF 8.3 ± 0.20 µm/h). Cell movement was directed strikingly to the anode of the EF for both cell types. The quantitative indices for directional migration (FMIx) of controls were -0.023 ± 0.045 and 0.001 ± 0.029 for unsorted and SMSCs, respectively but during EF exposure they were 0.651 ± 0.010 and 0.490 ± 0.013 for unsorted and SMSCs, respectively (p<0.01 for both). Unsorted cells displayed randomly oriented cell division relative to the EF, with the mitotic spindle oriented at mean angle 40 ± 7 degrees (n=16; p=0.2) compared to 50 ± 5 degrees for controls (n=20). In contrast, the mitotic spindle of sorted cells was more orthogonal to the EF, with a mean angle 52 ± 2 degrees (n=138) compared to 47 ± 2 degrees for controls (n=173; p<0.05). The data support the idea that EF stimulation coupled with cell therapies may aid tissue regeneration.
Physiology 2019 (Aberdeen, UK) (2019) Proc Physiol Soc 43, PC094
Poster Communications: Electric fields stimulate directional migration of synovial mesenchymal stem cells
S. G. Yayman1, A. Molsberger2,3, A. M. Rajnicek1, C. Mccaig1
1. Institute of medical sciences, University of Aberdeen, Aberdeen, United Kingdom. 2. Department of Orthopedics, Ruhr-University Bochum, Bochum, Germany. 3. Clinic for Orthopedics and Pain Treatment, Düsseldorf, Germany.
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Where applicable, experiments conform with Society ethical requirements.