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Directed Migration of Embryonic Stem Cell-derived Neural Cells In An Applied Electric Field

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Abstract

Spinal cord injury or diseases, such as amyotrophic lateral sclerosis, can cause the loss of motor neurons and therefore results in the paralysis of muscles. Stem cells may improve functional recovery by promoting endogenous regeneration, or by directly replacing neurons. Effective directional migration of grafted neural cells to reconstruct functional connections is crucial in the process. Steady direct current electric fields (EFs) play an important role in the development of the central nervous system. A strong biological effect of EFs is the induction of directional cell migration. In this study, we investigated the guided migration of embryonic stem cell (ESC) derived presumptive motor neurons in an applied EF. The dissociated mouse ESC derived presumptive motor neurons or embryoid bodies were subjected to EFs stimulation and the cell migration was studied. We found that the migration of neural precursors from embryoid bodies was toward cathode pole of applied EFs. Single motor neurons migrated to the cathode of the EFs and reversal of EFs poles reversed their migration direction. The directedness and displacement of cathodal migration became more significant when the field strength was increased from 50 mV/mm to 100 mV/mm. EFs stimulation did not influence the cell migration velocity. Our work suggests that EFs may serve as a guidance cue to direct grafted cell migration in vivo.

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Acknowledgements

This work was supported by Li Yao’s start-up funding, Wichita State University and National Center for Research Resources (P20 RR016475) and the National Institute of General Medical Sciences (P20 GM103418) from the National Institutes of Health. MLW’s laboratory is supported by the State of Kansas to the Midwest Institute of Comparative Stem Cell Biology, NSF Award: 1321261, NIH R01AR056347, the Dean’s office of the Kansas State University’s College of Veterinary Medicine, and gifts from Ronald Deffenbaugh Foundation and the Northeast Kansas Parkinson’s Association Research Fund. We acknowledge James Hong, Dr. Pavan Rajanahalli, and Dr. Hong He for advice and technical support.

Conflict of interest

The authors indicate no potential conflicts of interest.

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Authors and Affiliations

  1. Department of Biological Sciences, Wichita State University, Wichita, KS, 67260, USA

    Yongchao Li & Li Yao

  2. Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, 66506, USA

    Mark Weiss

Authors
  1. Yongchao Li
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  2. Mark Weiss
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  3. Li Yao
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Correspondence to Li Yao.

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Supplemental figure 1

Orientation of the cells that migrated out of the EBs. The EBs were labelled with anti-nestin antibody (green) and Rhodamine Phalloidin (red). (A, B) The cells that migrated out the EB without EFs stimulation appeared to be randomly oriented.(C, D) In contrast, in EFs, the cells that migrated out of the EB margins showed a clear re-orientation: On the cathode-facing side (right), most cells migrated parallel to the field line of EFs. On the anode-facing side (left), most cells oriented perpendicular to the field line of EFs. (GIF 120 kb)

High resolution image (TIFF 1431 kb)

Supplemental figure 2

Frequency distribution of the angles. The histograms show the frequency distribution of the angles of the cells after the first hour and the second hour of migration. In the first hour, time-lapse images recorded the random migration of the cells. In the second hour, time-lapse images recorded either the apparent random migration of the cells (figure A, control) or the directed cell migration in response to an applied EF (figure B, 50mV/mm; figure C, 100mV/mm). The positions of the cells after migrating for 1 hour in an EF fall within the given 20° sectors with respect to the direction of the imposed EFs (0°). Since this response is symmetrical about the 0-180° axis, the number of cells in each 20° sector between 20° and 160° is added with the number of cells in the symmetrical sector on the opposite side of the y axis and the total number was plotted. The cell number in the sectors centered on 0° and 180° represent the absolute number of cells in their respective 20° sectors (GIF 26 kb)

High resolution image (TIFF 272 kb)

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Li, Y., Weiss, M. & Yao, L. Directed Migration of Embryonic Stem Cell-derived Neural Cells In An Applied Electric Field. Stem Cell Rev and Rep 10, 653–662 (2014). https://doi.org/10.1007/s12015-014-9518-z

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  • DOI: https://doi.org/10.1007/s12015-014-9518-z

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