Charge-Balanced Electrical Stimulation Can Modulate Neural Precursor Cell Migration in the Presence of Endogenous Electric Fields in Mouse Brains

Overview

Journal eNeuro

Specialty Neurology

Date 2019 Nov 28

PMID 31772032

Citations 12

Authors

Stephanie N Iwasa

Abdolazim Rashidi

Elana Sefton

Nancy X Liu

Milos R Popovic

Cindi M Morshead

Affiliations

Soon will be listed here.

Abstract

Electric fields (EFs) can direct cell migration and are crucial during development and tissue repair. We previously reported neural precursor cells (NPCs) are electrosensitive cells that can undergo rapid and directed migration towards the cathode using charge-balanced electrical stimulation Here, we investigate the ability of electrical stimulation to direct neural precursor migration in mouse brains To visualize migration, fluorescent adult murine neural precursors were transplanted onto the corpus callosum of adult male mice and intracortical platinum wire electrodes were implanted medial (cathode) and lateral (anode) to the injection site. We applied a charge-balanced biphasic monopolar stimulation waveform for three sessions per day, for 3 or 6 d. Irrespective of stimulation, the transplanted neural precursors had a propensity to migrate laterally along the corpus callosum, and applied stimulation affected that migration. Further investigation revealed an endogenous EF along the corpus callosum that correlated with the lateral migration, suggesting that the applied EF would need to overcome endogenous cues. There was no difference in transplanted cell differentiation and proliferation, or inflammatory cell numbers near the electrode leads and injection site comparing stimulated and implanted non-stimulated brains. Our results support that endogenous and applied EFs are important considerations for designing cell therapies for tissue repair

Citing Articles

Regulation of neural stem cells by innervating neurons.

Dittmann N, Chen L, Voronova A J Neurochem. 2025; 169(1):e16287.

PMID: 39775528 PMC: 11707326. DOI: 10.1111/jnc.16287.

Electrical Stimulation for Stem Cell-Based Neural Repair: Zapping the Field to Action.

Iwasa S, Liu X, Naguib H, Kalia S, Popovic M, Morshead C eNeuro. 2024; 11(9).

PMID: 39256040 PMC: 11391505. DOI: 10.1523/ENEURO.0183-24.2024.

Subthalamic nucleus but not entopeduncular nucleus deep brain stimulation enhances neurogenesis in the SVZ-olfactory bulb system of Parkinsonian rats.

Fauser M, Payonk J, Weber H, Statz M, Winter C, Hadar R Front Cell Neurosci. 2024; 18:1396780.

PMID: 38746080 PMC: 11091264. DOI: 10.3389/fncel.2024.1396780.

Incorporating Combinatorial Approaches to Encourage Targeted Neural Stem/Progenitor Cell Integration Following Transplantation in Spinal Cord Injury.

Pieczonka K, Fehlings M Stem Cells Transl Med. 2023; 12(4):207-214.

PMID: 36892546 PMC: 10108724. DOI: 10.1093/stcltm/szad008.

Short-Term Cortical Electrical Stimulation during the Acute Stage of Traumatic Brain Injury Improves Functional Recovery.

Wang L, Wei W, Ho P Biomedicines. 2022; 10(8).

PMID: 36009512 PMC: 9405844. DOI: 10.3390/biomedicines10081965.

References

Nusrat L, Livingston-Thomas J, Raguthevan V, Adams K, Vonderwalde I, Corbett D . Cyclosporin A-Mediated Activation of Endogenous Neural Precursor Cells Promotes Cognitive Recovery in a Mouse Model of Stroke. Front Aging Neurosci. 2018; 10:93. PMC: 5928138. DOI: 10.3389/fnagi.2018.00093. View

Huang Y, Hoffmann G, Wheeler B, Schiapparelli P, Quinones-Hinojosa A, Searson P . Cellular microenvironment modulates the galvanotaxis of brain tumor initiating cells. Sci Rep. 2016; 6:21583. PMC: 4761929. DOI: 10.1038/srep21583. View

Faiz M, Sachewsky N, Gascon S, Bang K, Morshead C, Nagy A . Adult Neural Stem Cells from the Subventricular Zone Give Rise to Reactive Astrocytes in the Cortex after Stroke. Cell Stem Cell. 2015; 17(5):624-34. DOI: 10.1016/j.stem.2015.08.002. View

Babona-Pilipos R, Droujinine I, Popovic M, Morshead C . Adult subependymal neural precursors, but not differentiated cells, undergo rapid cathodal migration in the presence of direct current electric fields. PLoS One. 2011; 6(8):e23808. PMC: 3166127. DOI: 10.1371/journal.pone.0023808. View

Brocker D, Grill W . Principles of electrical stimulation of neural tissue. Handb Clin Neurol. 2013; 116:3-18. DOI: 10.1016/B978-0-444-53497-2.00001-2. View

Morshead C, Benveniste P, Iscove N, van der Kooy D . Hematopoietic competence is a rare property of neural stem cells that may depend on genetic and epigenetic alterations. Nat Med. 2002; 8(3):268-73. DOI: 10.1038/nm0302-268. View

Hussaini S, Jun H, Cho C, Kim H, Kim W, Jang M . Heat-induced antigen retrieval: an effective method to detect and identify progenitor cell types during adult hippocampal neurogenesis. J Vis Exp. 2013; (78). PMC: 3857113. DOI: 10.3791/50769. View

Kuncel A, Grill W . Selection of stimulus parameters for deep brain stimulation. Clin Neurophysiol. 2004; 115(11):2431-41. DOI: 10.1016/j.clinph.2004.05.031. View

Babona-Pilipos R, Pritchard-Oh A, Popovic M, Morshead C . Biphasic monopolar electrical stimulation induces rapid and directed galvanotaxis in adult subependymal neural precursors. Stem Cell Res Ther. 2015; 6:67. PMC: 4413998. DOI: 10.1186/s13287-015-0049-6. View

10.

Thrivikraman G, Boda S, Basu B . Unraveling the mechanistic effects of electric field stimulation towards directing stem cell fate and function: A tissue engineering perspective. Biomaterials. 2017; 150:60-86. DOI: 10.1016/j.biomaterials.2017.10.003. View

11.

Babona-Pilipos R, Popovic M, Morshead C . A galvanotaxis assay for analysis of neural precursor cell migration kinetics in an externally applied direct current electric field. J Vis Exp. 2012; (68). PMC: 3490317. DOI: 10.3791/4193. View

12.

Babona-Pilipos R, Liu N, Pritchard-Oh A, Mok A, Badawi D, Popovic M . Calcium influx differentially regulates migration velocity and directedness in response to electric field application. Exp Cell Res. 2018; 368(2):202-214. DOI: 10.1016/j.yexcr.2018.04.031. View

13.

Bertucci C, Koppes R, Dumont C, Koppes A . Neural responses to electrical stimulation in 2D and 3D in vitro environments. Brain Res Bull. 2019; 152:265-284. DOI: 10.1016/j.brainresbull.2019.07.016. View

14.

Dadwal P, Mahmud N, Sinai L, Azimi A, Fatt M, Wondisford F . Activating Endogenous Neural Precursor Cells Using Metformin Leads to Neural Repair and Functional Recovery in a Model of Childhood Brain Injury. Stem Cell Reports. 2015; 5(2):166-73. PMC: 4618663. DOI: 10.1016/j.stemcr.2015.06.011. View

15.

Li Y, Wang X, Yao L . Directional migration and transcriptional analysis of oligodendrocyte precursors subjected to stimulation of electrical signal. Am J Physiol Cell Physiol. 2015; 309(8):C532-40. PMC: 4609655. DOI: 10.1152/ajpcell.00175.2015. View

16.

DAmico F, Skarmoutsou E, Stivala F . State of the art in antigen retrieval for immunohistochemistry. J Immunol Methods. 2008; 341(1-2):1-18. DOI: 10.1016/j.jim.2008.11.007. View

17.

Lois C, Alvarez-Buylla A . Long-distance neuronal migration in the adult mammalian brain. Science. 1994; 264(5162):1145-8. DOI: 10.1126/science.8178174. View

18.

Cayre M, Bancila M, Virard I, Borges A, Durbec P . Migrating and myelinating potential of subventricular zone neural progenitor cells in white matter tracts of the adult rodent brain. Mol Cell Neurosci. 2006; 31(4):748-58. DOI: 10.1016/j.mcn.2006.01.004. View

19.

Baer M, Henderson S, Colello R . Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System. PLoS One. 2015; 10(11):e0142740. PMC: 4643040. DOI: 10.1371/journal.pone.0142740. View

20.

Morrison T, Sefton E, Marquez-Chin M, Popovic M, Morshead C, Naguib H . A 3D Printed Device for Low Cost Neural Stimulation in Mice. Front Neurosci. 2019; 13:784. PMC: 6682623. DOI: 10.3389/fnins.2019.00784. View