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Low current electrical stimulation upregulates cytokine expression in the anal sphincter

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Aim

Stem cells are an emerging treatment for regeneration of damaged anal sphincter tissues. Homing to the site of injury can be potentiated by stromal derived factor 1 (SDF-1) and monocyte chemotactic protein 3 (MCP-3) expression. The effects of electrical stimulation (ES) on upregulation of these cytokines were investigated.

Methods

The anal sphincter complex of Sprague Dawley rats was stimulated with current of 0.25 mA, pulse duration of 40 pulses/s, pulse width of 100 μs, and frequency of 100 Hz for 1 or 4 h. Sham was created using the same needle which was inserted into the anal sphincter without electrical stimulation in different groups of animals. The rats were euthanized immediately or 24 h after stimulation. Cytokine analysis was performed using real-time polymerase chain reaction. Statistical analysis was performed.

Results

Results are presented as a fold increase compared to sham that was normalized to 1. SDF-1 and MCP-3 immediately after 1 h were 2.5 ± 0.77 and 3.1 ± 0.93 vs. sham, respectively, showing significant increase. After 1-h stimulation and euthanasia 24 h after, SDF-1 and MCP-3 were 1.49 ± 0.16 and 1.51 ± 0.14 vs. sham, respectively, showing significant increase. Immediately and 24 h after 4-h stimulation, SDF-1 was 1.21 ± 0.16 and 0.54 ± 0.16 vs. sham, respectively, and was not significantly different. Immediately and 24 h after 4-h stimulation, MCP-3 was 1.29 ± 0.41 and 0.35 ± 1.0 vs. sham, respectively, and was not significantly different. SDF-1 and MCP-3 after 1 h were significantly higher than after 4 h of stimulation at both time points.

Conclusion

Electrical stimulation for 1 h significantly upregulates SDF-1 and MCP-3 expression that persists for 24 h. Prolonged stimulation reduced chemokine expression, suggesting electrolysis of cells.

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Notes

  1. Relative Quantitation Using Comparative CT Assay Getting Started Guide, 2006, Applied Biosystems, USA.

References

  1. Donnelly V, Fynes M, Campbell D et al (1998) Obstetric events leading to anal sphincter damage. Obstet Gynecol 92(6):955–961

    Article  PubMed  CAS  Google Scholar 

  2. Madoff RD (2004) Surgical treatment options for fecal incontinence. Gastroenterology 126:S48–S54

    Article  PubMed  Google Scholar 

  3. Bittinger M, Barnert J, Moll A et al (1996) Medical therapy of fecal incontinence. Zentralblatt fur Chirurgie 121:665–668

    PubMed  CAS  Google Scholar 

  4. Feki A, Faltin DL, Lei T et al (2007) Sphincter incontinence: is regenerative medicine the best alternative to restore urinary or anal sphincter function? Int J Biochem Cell Biol 39:678–684

    Article  PubMed  CAS  Google Scholar 

  5. Schenk S, Mal N, Finan A et al (2007) Monocyte chemotactic protein-3 is a myocardial mesenchymal stem cell homing factor. Stem Cells 25:245–251

    Article  PubMed  CAS  Google Scholar 

  6. Aaron RK, Ciombor DM, Wang S et al (2006) Clinical biophysics: the promotion of skeletal repair by physical forces. Skelet Dev Remodel Health Dis Aging 1068:513–531

    CAS  Google Scholar 

  7. Genovese JA, Spadaccio C, Langer J et al (2008) Electrostimulation induces cardiomyocyte predifferentiation of fibroblasts. Biochem Biophys Res Commun 370:450–455

    Article  PubMed  CAS  Google Scholar 

  8. Zhao M, Bai H, Wang E et al (2004) Electrical stimulation directly induces pre-angiogenic responses in vascular endothelial cells by signaling through VEGF receptors. J Cell Sci 117:397–405

    Article  PubMed  CAS  Google Scholar 

  9. Maione F, Paschalidis N, Mascolo N et al (2009) Interleukin 17 sustains rather than induces inflammation. Biochem Pharmacol 77:878–887

    Article  PubMed  CAS  Google Scholar 

  10. Zhang M, Mal N, Kiedrowski M et al (2007) SDF-1 expression by mesenchymal stem cells results in trophic support of cardiac myocytes after myocardial infarction. FASEB J 21:3197–3207

    Article  PubMed  CAS  Google Scholar 

  11. Woo LL, Hijaz A, Kuang M et al (2007) Over expression of stem cell homing cytokines in urogenital organs following vaginal distention. J Urol 177:1568–1572

    Article  PubMed  CAS  Google Scholar 

  12. Nath C, Gulati SC (1998) Role of cytokines in healing chronic skin wounds. Acta Haematol 99:175–179

    Article  PubMed  CAS  Google Scholar 

  13. Spadaro JA (1997) Mechanical and electrical interactions in bone remodeling. Bioelectromagnetics 18:193–202

    Article  PubMed  CAS  Google Scholar 

  14. Karavidas AI, Raisakis KG, Parissis JT et al (2006) Functional electrical stimulation improves endothelial function and reduces peripheral immune responses in patients with chronic heart failure. Eur J Cardiovasc Prev & Rehabil 13:592–597

    Article  Google Scholar 

  15. Kim IS, Song JK, Zhang YL et al (2006) Biphasic electric current stimulates proliferation and induces VEGF production in osteoblasts. Biochim Biophys Acta Mol Cell Res 1763:907–916

    Article  CAS  Google Scholar 

  16. Serena E, Flaibani M, Carnio S et al (2008) Electrophysiologic stimulation improves myogenic potential of muscle precursor cells grown in a 3D collagen scaffold. Neurol Res 30:207–214

    Article  PubMed  CAS  Google Scholar 

  17. Chaliha C, Sultan AH, Bland JM, Monga AK, Stanton SL (2001) Anal function: effect of pregnancy and delivery. Am J Obstet Gynecol 185:427–432

    Article  PubMed  CAS  Google Scholar 

  18. Starkman JS, Wolter CE, Scarpero HM et al (2007) Management of refractory urinary urge incontinence following urogynecological surgery with sacral neuromodulation. Neurourol Urodyn 26:29–35

    Article  PubMed  Google Scholar 

  19. Healy CF, Brannigan AE, Connolly EM et al (2006) The effects of low-frequency endo-anal electrical stimulation on faecal incontinence: a prospective study. Int J Color Dis 21:802–806

    Article  Google Scholar 

  20. Hosker G, Cody JD, Norton CC (2007) Electrical stimulation for faecal incontinence in adults. Cochrane Database of Systematic Reviews

  21. Pelliccioni G, Scarpino O (2006) External anal sphincter responses after S3 spinal root surface electrical stimulation. Neurourol Urodyn 25:788–791

    Article  PubMed  Google Scholar 

  22. Russo TL, Peviani SM, Durigan JLQ et al (2008) Electrical stimulation increases matrix metalloproteinase-2 gene expression but does not change its activity in denervated rat muscle. Muscle Nerve 37:593–600

    Article  PubMed  CAS  Google Scholar 

  23. Miller MD, Krangel MS (1992) Biology and biochemistry of the chemokines—a family of chemotactic and inflammatory cytokines. Crit Rev Immunol 12:17–46

    PubMed  CAS  Google Scholar 

  24. Miller RJ, Tran PB (2005) Chemokinetics. Neuron 47:621–623

    Article  PubMed  CAS  Google Scholar 

  25. Tran PB, Banisadr G, Ren DJ et al (2007) Chemokine receptor expression by neural progenitor cells in neurogenic regions of mouse brain. J Comp Neurol 500:1007–1033

    Article  PubMed  CAS  Google Scholar 

  26. Croft AP, Przyborski SA (2009) Mesenchymal stem cells expressing neural antigens instruct a neurogenic cell fate on neural stem cells. Exp Neurol 216:329–341

    Article  PubMed  CAS  Google Scholar 

  27. OFarrell AM, Ichihara M, Mui ALF et al (1996) Signaling pathways activated in a unique mast cell line where interleukin-3 supports survival and stem cell factor is required for a proliferative response. Blood 87:3655–3668

    CAS  Google Scholar 

  28. Miller RJ, Banisadr G, Bhattacharyya BJ (2008) CXCR4 signaling in the regulation of stem cell migration and development. J Neuroimmunol 198:31–38

    Article  PubMed  CAS  Google Scholar 

  29. Penn MS, Khalil MK (2008) Exploitation of stem cell homing for gene delivery. Expert Opin Biol Ther 8:17–30

    Article  PubMed  CAS  Google Scholar 

  30. Unzek S, Zhang M, Mal N et al (2007) SDF-1 recruits cardiac stem cell-like cells that depolarize in vivo. Cell Transplant 16:879–886

    Article  PubMed  Google Scholar 

  31. Fredsted A, Mikkelsen UR, Gissel H et al (2005) Anoxia induces Ca2+ influx and loss of cell membrane integrity in rat extensor digitorum longus muscle. Exp Physiol 90:703–714

    Article  PubMed  CAS  Google Scholar 

  32. Ceradini DJ, Gurtner GC (2005) Homing to hypoxia: HIF-1 as a mediator of progenitor cell recruitment to injured tissue. Trends Cardiovasc Med 15:57–63

    Article  PubMed  CAS  Google Scholar 

  33. Fujita M, Furukawa Y, Nagasawa Y et al (2000) Down-regulation of monocyte chemotactic protein-3 by activated beta-catenin. Cancer Res 60:6683–6687

    PubMed  CAS  Google Scholar 

  34. Theiss HD, Vallaster M, Rischpler C, Krieg L, et al (2011) Dual stem cell therapy after myocardial infarction acts specifically by enhanced homing via the SDF-1/CXCR4 axis. Stem cell research

  35. Salcedo L, Sopko N, Jiang HH, Damaser M, Penn M, Zutshi M (2011) Chemokine upregulation in response to anal sphincter and pudendal nerve injury: potential signals for stem cell homing. Int J Colorectal Dis. doi:10.1007/s00384-011-1269-6

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Acknowledgment

This work was supported by the Research Protocol Committee of the Department of Colorectal Surgery, Cleveland Clinic, and the Department of Biomedical Engineering. The authors would like to thank Brian Balog and Paul Zaszczurynski for assistance and expertise.

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Authors and Affiliations

  1. Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH, USA

    Levilester Salcedo, Lei Lian & Massarat Zutshi

  2. Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH, USA

    Hai-Hong Jiang & Margot Damaser

  3. Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, OH, USA

    Nikolai Sopko & Marc Penn

Authors
  1. Levilester Salcedo
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  2. Lei Lian
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  3. Hai-Hong Jiang
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  4. Nikolai Sopko
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  5. Marc Penn
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  6. Margot Damaser
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  7. Massarat Zutshi
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Corresponding author

Correspondence to Massarat Zutshi.

Additional information

This was a research forum podium presentation at the American Society of Colon and Rectal Surgery 2009, Hollywood, Florida.

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Salcedo, L., Lian, L., Jiang, HH. et al. Low current electrical stimulation upregulates cytokine expression in the anal sphincter. Int J Colorectal Dis 27, 221–225 (2012). https://doi.org/10.1007/s00384-011-1324-3

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  • DOI: https://doi.org/10.1007/s00384-011-1324-3

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