Skip to main content
SpringerLink
Log in

Method of Combined Intermittent Hypoxia and Surface Muscle Electrostimulation for Enhancing Peripheral Stem Cells in Humans

  • Chapter
  • First Online:
Intermittent Hypoxia and Human Diseases

  • 919 Accesses

Abstract

Short-term intermittent hypoxia exposure, at a level well tolerated by healthy humans and previously shown by our group to increase erythropoietin and erythropoiesis, could mobilize hematopoietic stem cells (HSC) and increase their presence in peripheral circulation. Four healthy male volunteers were subjected to three protocols: one with only hypoxic stimulus (OH), another with hypoxic stimulus plus muscle electrostimulation (HME), and the third with only muscle electrostimulation (OME). Intermittent hypobaric hypoxia exposure consisted of three sessions of 3 h inside a hypobaric chamber at a barometric pressure 535 hPa (equivalent to an altitude of 5,000 m) for 3 consecutive days. Muscular electrostimulation was performed in two separate periods of 25 min within each session. Blood samples were obtained from an antecubital vein on 3 consecutive days immediately before the experiment and 24, 48 h, 4, and 7 days after the last day of hypoxic exposure. There was a clear increase in the number of circulating CD34+ cells but only after the experimental program combining hypobaric hypoxia and muscular electrostimulation. This response was not observed after the isolated application of the same stimuli. Our results open a new application field for intermittent hypobaric hypoxia as a way to increase peripheral HSC concentration. Muscle electrostimulation combined with hypoxia can be a useful tool for patients with a wide variety of conditions limiting classical physical exercise.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

CXCR4:

CXC receptor 4

EPO:

Erythropoietin

FITC:

Fluorescein isothiocyanate

G-CSF:

Granulocyte colony-stimulating factor

HME:

Hypoxic stimulus plus muscle electrostimulation

HSCs:

Hematopoietic stem cells

IH:

Intermittent hypoxia

OH:

Only hypoxic stimulus

OME:

Only muscle electrostimulation

SCs:

Stem cells

SDF1:

Stromal-derived factor 1

References

  1. Adams V, Lenk K, Linke A, et al. Increase of circulating endothelial progenitor cells in patients with coronary artery disease after exercise-induced ischemia. Arterioscler Thromb Vasc Biol. 2004; 24:684–90.

    Article  PubMed  CAS  Google Scholar 

  2. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964–7.

    Article  PubMed  CAS  Google Scholar 

  3. Assmus B, Schachinger V, Teupe C, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation. 2002;106:3009–17.

    Article  PubMed  Google Scholar 

  4. Bahlmann FH, de Groot K, Spandau J, et al. Erythropoietin regulates endothelial progenitor cells. Blood. 2004;103:921–6.

    Article  PubMed  CAS  Google Scholar 

  5. Bennie SD, Petrofsky JS, Nisperos J, et al. Toward the optimal waveform for electrical stimulation of human muscle. Eur J Appl Physiol. 2002;88:13–9.

    Article  PubMed  Google Scholar 

  6. Bonsignore MR, Morici G, Riccioni R, et al. Hemopoietic and angiogenetic progenitors in healthy athletes: different responses to endurance and maximal exercise. J Appl Physiol. 2010;109:60–7.

    Article  PubMed  CAS  Google Scholar 

  7. Brocherie F, Babault N, Cometti G, et al. Electrostimulation training effects on the physical performance of ice hockey players. Med Sci Sports Exerc. 2005;37:455–60.

    Article  PubMed  Google Scholar 

  8. Burtscher M, Pachinger O, Ehrenbourg I, et al. Intermittent hypoxia increases exercise tolerance in elderly men with and without coronary artery disease. Int J Cardiol. 2004;96:247–54.

    Article  PubMed  Google Scholar 

  9. Casas M, Casas H, Pagès T, et al. Intermittent hypobaric hypoxia induces altitude acclimation and improves the lactate threshold. Aviat Space Environ Med. 2000;71:125–30.

    PubMed  CAS  Google Scholar 

  10. Cashen AF, Lazarus HM, Devine SM. Mobilizing stem cells from normal donors: is it possible to improve upon G-CSF? Bone Marrow Transplant. 2007;39:577–88.

    Article  PubMed  CAS  Google Scholar 

  11. Crameri RM, Weston A, Climstein M, et al. Effects of electrical stimulation-induced leg training on skeletal muscle adaptability in spinal cord injury. Scand J Med Sci Sports. 2002;12:316–22.

    Article  PubMed  CAS  Google Scholar 

  12. Esteva S, Panisello P, Torrella JR, et al. Blood rheology adjustments in rats after a program of intermittent exposure to hypobaric hypoxia. High Alt Med Biol. 2009;10:275–81.

    Article  PubMed  Google Scholar 

  13. Esteva S, Panisello P, Ramon Torrella J, et al. Enzyme activity and myoglobin concentration in rat myocardium and skeletal muscles after passive intermittent simulated altitude exposure. J Sports Sci. 2009;27:633–40.

    Article  PubMed  Google Scholar 

  14. Falanga A, Marchetti M, Evangelista V, et al. Neutrophil activation and hemostatic changes in healthy donors receiving granulocyte colony-stimulating factor. Blood. 1999;93:2506–14.

    PubMed  CAS  Google Scholar 

  15. Ferrario M, Massa M, Rosti V, et al. Early haemoglobin-independent increase of plasma erythropoietin levels in patients with acute myocardial infarction. Eur Heart J. 2007;28:1805–13.

    Article  PubMed  CAS  Google Scholar 

  16. Flames N, Pla R, Gelman DM, et al. Delineation of multiple subpallial progenitor domains by the combinatorial expression of transcriptional codes. J Neurosci. 2007;27:9682–95.

    Article  PubMed  CAS  Google Scholar 

  17. Grayson W, Zhao F, Bunnell B, et al. Hypoxia enhances proliferation and tissue formation of human mesenchymal stem cells. Biochem Biophys Res Commun. 2007;358:948–53.

    Article  PubMed  CAS  Google Scholar 

  18. Gutierrez-Delgado F, Bensinger W. Safety of granulocyte colony-stimulating factor in normal donors. Curr Opin Hematol. 2001;8:155–60.

    Article  PubMed  CAS  Google Scholar 

  19. Hoetzer GL, Van Guilder GP, Irmiger HM, et al. Aging, exercise, and endothelial progenitor cell clonogenic and migratory capacity in men. J Appl Physiol. 2007;102:847–52.

    Article  PubMed  Google Scholar 

  20. Katayama K, Ishida K, Iwasaki K, et al. Effect of two durations of short-term intermittent hypoxia on ventilatory chemosensitivity in humans. Eur J Appl Physiol. 2009;105:815–21.

    Article  PubMed  Google Scholar 

  21. Keeney M, Chin-Yee I, Weir K, et al. Single platform flow cytometric absolute CD34+ cell counts based on the ISHAGE guidelines. International Society of Hematotherapy and Graft Engineering. Cytometry. 1998;34:61–70.

    Article  PubMed  CAS  Google Scholar 

  22. Kondo T, Hayashi M, Takeshita K, et al. Smoking cessation rapidly increases circulating progenitor cells in peripheral blood in chronic smokers. Arterioscler Thromb Vasc Biol. 2004;24:1442–7.

    Article  PubMed  CAS  Google Scholar 

  23. Koutedakis Y, Frischknecht R, Vrbova G, et al. Maximal voluntary quadriceps strength patterns in Olympic overtrained athletes. Med Sci Sports Exerc. 1995;27:566–72.

    PubMed  CAS  Google Scholar 

  24. Laufs U, Urhausen A, Werner N, et al. Running exercise of different duration and intensity: effect on endothelial progenitor cells in healthy subjects. Eur J Cardiovasc Prev Rehabil. 2005;12:407–14.

    Article  PubMed  Google Scholar 

  25. Levine BD, Stray-Gundersen J. “Living high-training low”: effect of moderate-altitude acclimatization with low-altitude training on performance. J Appl Physiol. 1997;83:102–12.

    PubMed  CAS  Google Scholar 

  26. Levine BD. Intermittent hypoxic training: fact and fancy. High Alt Med Biol. 2002;3:177–93.

    Article  PubMed  Google Scholar 

  27. Meng X, Ichim T, Zhong J, et al. Endometrial regenerative cells: a novel stem cell population. J Transl Med. 2007;5:57.

    Article  PubMed  CAS  Google Scholar 

  28. Miller-Kasprzak E, Jagodzinski PP. Endothelial progenitor cells as a new agent contributing to vascular repair. Arch Immunol Ther Exp (Warsz). 2007;55:247–59.

    Article  CAS  Google Scholar 

  29. Mobius-Winkler S, Hilberg T, Menzel K, et al. Time-dependent mobilization of circulating progenitor cells during strenuous exercise in healthy individuals. J Appl Physiol. 2009;107:1943–50.

    Article  PubMed  Google Scholar 

  30. Panisello P, Torrella JR, Esteva S, et al. Capillary supply, fibre types and fibre morphometry in rat tibialis anterior and diaphragm muscles after intermittent exposure to hypobaric hypoxia. Eur J Appl Physiol. 2008;103:203–13.

    Article  PubMed  Google Scholar 

  31. Panisello P, Esteva S, Torrella R, et al. Intermittent hypobaric hypoxia induces changes at a different extent in biochemical parameters depending on muscle activity degree. Comp Biochem Physiol A Mol Integr Physiol. 2007;146:S184.

    Article  Google Scholar 

  32. Perez AL, Bachrach E, Illigens BM, et al. CXCR4 enhances engraftment of muscle progenitor cells. Muscle Nerve. 2009; 40:562–72.

    Article  PubMed  CAS  Google Scholar 

  33. Perin EC, Dohmann HF, Borojevic R, et al. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation. 2003;107:2294–302.

    Article  PubMed  Google Scholar 

  34. Qiang X, Shaoxia W, Xijuan J, et al. Hypoxia-induced astrocytes promote the migration of neural progenitor cells via vascular endothelial factor, stem cell factor, stromal-derived factor-1α and monocyte chemoattractant protein-1 upregulation in vitro. Clin Exp Pharmacol Physiol. 2007;34:624–31.

    Article  Google Scholar 

  35. Ricart A, Casas H, Casas M, et al. Acclimatization near home? Early respiratory changes after short-term intermittent exposure to simulated altitude. Wilderness Environ Med. 2000;11:84–8.

    Article  PubMed  CAS  Google Scholar 

  36. Roberts N, Xiao Q, Weir G, et al. Endothelial progenitor cells are mobilized after cardiac surgery. Ann Thorac Surg. 2007;83:598–605.

    Article  PubMed  Google Scholar 

  37. Rodriguez FA, Ventura JL, Casas M, et al. Erythropoietin acute reaction and haematological adaptations to short, intermittent hypobaric hypoxia. Eur J Appl Physiol. 2000;82:170–7.

    Article  PubMed  CAS  Google Scholar 

  38. Rodriguez FA, Casas H, Casas M, et al. Intermittent hypobaric hypoxia stimulates erythropoiesis and improves aerobic capacity. Med Sci Sports Exerc. 1999;31:264–8.

    Article  PubMed  CAS  Google Scholar 

  39. Serebrovskaya TV, Nikolsky IS, Nikolska VV, et al. Intermittent hypoxia mobilizes hematopoietic progenitors and augments cellular and humoral elements of innate immunity in adult men. High Alt Med Biol. 2011;12:243–52.

    Article  PubMed  CAS  Google Scholar 

  40. Serebrovskaya TV. Intermittent hypoxia research in the former Soviet Union and the Commonwealth of independent states: history and review of the concept and selected applications. High Alt Med Biol. 2002;3:205–21.

    Article  PubMed  Google Scholar 

  41. Shatilo VB, Korkushko OV, Ischuk VA, et al. Effects of intermittent hypoxia training on exercise performance, hemodynamics, and ventilation in healthy senior men. High Alt Med Biol. 2008;9:43–52.

    Article  PubMed  Google Scholar 

  42. Shintani S, Murohara T, Ikeda H, et al. Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation. 2001;103:2776–9.

    Article  PubMed  CAS  Google Scholar 

  43. Stamm C, Westphal B, Kleine HD, et al. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet. 2003;361:45–6.

    Article  PubMed  Google Scholar 

  44. Steiner S, Niessner A, Ziegler S, et al. Endurance training increases the number of endothelial progenitor cells in patients with cardiovascular risk and coronary artery disease. Atherosclerosis. 2005; 181:305–10.

    Article  PubMed  CAS  Google Scholar 

  45. Theiss HD, David R, Engelmann MG, et al. Circulation of CD34+ progenitor cell populations in patients with idiopathic dilated and ischaemic cardiomyopathy (DCM and ICM). Eur Heart J. 2007; 28:1258–64.

    Article  PubMed  Google Scholar 

  46. Thijssen DH, Vos JB, Verseyden C, et al. Haematopoietic stem cells and endothelial progenitor cells in healthy men: effect of aging and training. Aging Cell. 2006;5:495–503.

    Article  PubMed  CAS  Google Scholar 

  47. Tilling L, Chowienczyk P, Clapp B. Progenitors in motion: mechanisms of mobilization of endothelial progenitor cells. Br J Clin Pharmacol. 2009;68:484–92.

    Article  PubMed  CAS  Google Scholar 

  48. Valgimigli M, Rigolin GM, Cittanti C, et al. Use of granulocyte-colony stimulating factor during acute myocardial infarction to enhance bone marrow stem cell mobilization in humans: clinical and angiographic safety profile. Eur Heart J. 2005;26:1838–45.

    Article  PubMed  CAS  Google Scholar 

  49. Valina C, Pinkernell K, Song Y, et al. Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction. Eur Heart J. 2007;28:2667–77.

    Article  PubMed  Google Scholar 

  50. Wahl P, Brixius K, Bloch W. Exercise-induced stem cell activation and its implication for cardiovascular and skeletal muscle regeneration. Minim Invasive Ther Allied Technol. 2008;17:91–9.

    Article  PubMed  Google Scholar 

  51. Werner N, Kosiol S, Schiegl T, et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med. 2005;353:999–1007.

    Article  PubMed  CAS  Google Scholar 

  52. Westenbrink BD, Lipsic E, van der Meer P, et al. Erythropoietin improves cardiac function through endothelial progenitor cell and vascular endothelial growth factor mediated neovascularization. Eur Heart J. 2007;28:2018–27.

    Article  PubMed  CAS  Google Scholar 

  53. Zhu L, Zhao T, Li H, et al. Neurogenesis in the adult rat brain after intermittent hypoxia. Brain Res. 2005;1055:1–6.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are grateful to Dr. Gregorio Martín-Henao and Ms. Carmen Azqueta from Unitat de Teràpia Cel·lular (Centre de Transfusió i Banc de Teixits) for their key contribution in HSC quantification. We also acknowledge Mr. Víctor Gómez for his kind support to our research group and for his critical participation in the installation of the hypobaric chamber and annexed facilities. We are also grateful to Mr. Juan A. Silva from Universidad de Antofagasta (Chile) by his collaboration in some data collection, and to Mr. Robin Rycroft (Language Advice Service, Universitat de Barcelona) for his useful help in editing the manuscript. Finally, we wish to express our gratitude and appreciation to Prof. Ramon Segura for his mentoring tasks of our research group and to Prof. Luis Palacios for his support and ideas and his pioneering impulse on hypobaric studies.

Competing Interests

This study was performed without support from any public or private fund, agency, or company. The authors declare that they have no competing interests. This chapter is based on a previous study that was published in J Transl Med (2009) 7:91.

Author information

Authors and Affiliations

  1. Departament de Fisiologia i Immunologia, Universitat de Barcelona, Av. Diagonal, 643, E-08028, Barcelona, Spain

    Ginés Viscor, Teresa Pagès & Joan Ramon Torrella

  2. Departament de Ciències Fisiològiques II, Universitat de Barcelona, IDIBELL, Feixa Llarga s/n, L’Hospitalet de Llobregat, E-08907, Barcelona, Spain

    Casimiro Javierre & Luisa Corral

  3. Servei de Medicina Intensiva, Hospital Universitari de Bellvitge, IDIBELL, Feixa Llarga s/n, E-08907, L’Hospitalet de Llobregat, Barcelona, Spain

    Luisa Corral, Antoni Ricart & Josep Lluis Ventura

Authors
  1. Ginés Viscor
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Casimiro Javierre
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Teresa Pagès
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Luisa Corral
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Joan Ramon Torrella
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Antoni Ricart
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Josep Lluis Ventura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ginés Viscor .

Editor information

Editors and Affiliations

  1. , Division of Cardiology, Virginia Commonwealth University, Richmond, 23298, Virginia, USA

    Lei Xi

  2. Bogomoletz Institute of Physiology, Kiev, 01601, Ukraine

    Tatiana V. Serebrovskaya

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag London

About this chapter

Cite this chapter

Viscor, G. et al. (2012). Method of Combined Intermittent Hypoxia and Surface Muscle Electrostimulation for Enhancing Peripheral Stem Cells in Humans. In: Xi, L., Serebrovskaya, T. (eds) Intermittent Hypoxia and Human Diseases. Springer, London. https://doi.org/10.1007/978-1-4471-2906-6_25

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-2906-6_25

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-2905-9

  • Online ISBN: 978-1-4471-2906-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation