Combined intermittent hypoxia and surface muscle electrostimulation as a method to increase peripheral blood progenitor cell concentration

Ginés Viscor, Casimiro Javierre, Teresa Pagès, Josep-Lluis Ventura, Antoni Ricart, Gregorio Martin-Henao, Carmen Azqueta, Ramon Segura, Ginés Viscor, Casimiro Javierre, Teresa Pagès, Josep-Lluis Ventura, Antoni Ricart, Gregorio Martin-Henao, Carmen Azqueta, Ramon Segura

Abstract

Background: Our goal was to determine whether short-term intermittent hypoxia exposure, at a level well tolerated by healthy humans and previously shown by our group to increase EPO and erythropoiesis, could mobilize hematopoietic stem cells (HSC) and increase their presence in peripheral circulation.

Methods: Four healthy male subjects were subjected to three different protocols: one with only a hypoxic stimulus (OH), another with a hypoxic stimulus plus muscle electrostimulation (HME) and the third with only muscle electrostimulation (OME). Intermittent hypobaric hypoxia exposure consisted of only three sessions of three hours at barometric pressure 540 hPa (equivalent to an altitude of 5000 m) for three consecutive days, whereas muscular electrostimulation was performed in two separate periods of 25 min in each session. Blood samples were obtained from an antecubital vein on three consecutive days immediately before the experiment and 24 h, 48 h, 4 days and 7 days after the last day of hypoxic exposure.

Results: There was a clear increase in the number of circulating CD34+ cells after combined hypobaric hypoxia and muscular electrostimulation. This response was not observed after the isolated application of the same stimuli.

Conclusion: Our results open a new application field for hypobaric systems as a way to increase efficiency in peripheral HSC collection.

Figures

Figure 1
Figure 1
CD34+ cells after hypobaric hypoxia and muscle electrostimulation. Evolution of the CD34+ cell count (left axis; red bars) and percentage (right axis; blue circles) during the HME experimental set. Category medians and positive standard errors are shown for the two variables. A statistically significant increase for CD34+ concentration (cells/μL) was found (p = 0.009).

References

    1. Asahara T, Murohara T, Sullivan A, Silver M, Zee R van der, Li T, Witzenbichler B, Schatteman G, Isner JM. Isolation of putative progenitor endothelial cells for angiogenesis. Science (New York, N Y) 1997;275:964–967.
    1. Ferrario M, Massa M, Rosti V, Campanelli R, Ferlini M, Marinoni B, De Ferrari GM, Meli V, De Amici M, Repetto A, Verri A, Bramucci E, Tavazzi L. Early haemoglobin-independent increase of plasma erythropoietin levels in patients with acute myocardial infarction. Eur Heart J. 2007;28:1805–1813. doi: 10.1093/eurheartj/ehm065.
    1. Theiss HD, David R, Engelmann MG, Barth A, Schotten K, Naebauer M, Reichart B, Steinbeck G, Franz WM. Circulation of CD34+ progenitor cell populations in patients with idiopathic dilated and ischaemic cardiomyopathy (DCM and ICM) Eur Heart J. 2007;28:1258–1264. doi: 10.1093/eurheartj/ehm011.
    1. Roberts N, Xiao Q, Weir G, Xu Q, Jahangiri M. Endothelial Progenitor Cells are Mobilized After Cardiac Surgery. Ann Thorac Surg. 2007;83:598–605. doi: 10.1016/j.athoracsur.2006.09.087.
    1. Steiner S, Niessner A, Ziegler S, Richter B, Seidinger D, Pleiner J, Penka M, Wolzt M, Huber K, Wojta J, Minar E, Kopp CW. Endurance training increases the number of endothelial progenitor cells in patients with cardiovascular risk and coronary artery disease. Atherosclerosis. 2005;181:305–310. doi: 10.1016/j.atherosclerosis.2005.01.006.
    1. Hoetzer GL, Van Guilder GP, Irmiger HM, Keith RS, Stauffer BL, DeSouza CA. Aging, exercise, and endothelial progenitor cell clonogenic and migratory capacity in men. J Appl Physiol. 2007;102:847–852. doi: 10.1152/japplphysiol.01183.2006.
    1. Meng X, Ichim T, Zhong J, Rogers A, Yin Z, Jackson J, Wang H, Ge W, Bogin V, Chan K, Thebaud B, Riordan N. Endometrial regenerative cells: A novel stem cell population. Journal of Translational Medicine. 2007;5:57. doi: 10.1186/1479-5876-5-57.
    1. Kondo T, Hayashi M, Takeshita K, Numaguchi Y, Kobayashi K, Iino S, Inden Y, Murohara T. Smoking cessation rapidly increases circulating progenitor cells in peripheral blood in chronic smokers. Arterioscler Thromb Vasc Biol. 2004;24:1442–1447. doi: 10.1161/01.ATV.0000135655.52088.c5.
    1. Zhu Ll, Zhao T, Li Hs, Zhao H, Wu Ly, Ding As, Fan Wh, Fan M. Neurogenesis in the adult rat brain after intermittent hypoxia. Brain Res. 2005;1055:1–6. doi: 10.1016/j.brainres.2005.04.075.
    1. Qiang Xu, Penka M, Wolzt M, Huber K, Wojta J, Minar E, Kopp CW. Hypoxia-Induced Astrocytes Promote the Migration of Neural Progenitor Cells Via Vascular Endothelial Factor, Stem Cell Factor, Stromal-Derived Factor-1alpha and Monocyte Chemoattractant Protein-1 Upregulation in Vitro. Clin Exp Pharmacol Physiol. 2007;34:624–631. doi: 10.1111/j.1440-1681.2007.04619.x.
    1. Grayson W, Zhao F, Bunnell B, Ma T. Hypoxia enhances proliferation and tissue formation of human mesenchymal stem cells. Biochem Biophys Res Commun. 2007;358:948–953. doi: 10.1016/j.bbrc.2007.05.054.
    1. Flames N, Pla R, Gelman DM, Rubenstein JLR, Puelles L, Marin O. Delineation of Multiple Subpallial Progenitor Domains by the Combinatorial Expression of Transcriptional Codes. J Neurosci. 2007;27:9682–9695. doi: 10.1523/JNEUROSCI.2750-07.2007.
    1. Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Böhm M, Nickenig G. Circulating Endothelial Progenitor Cells and Cardiovascular Outcomes. N Engl J Med. 2005;353:999–1007. doi: 10.1056/NEJMoa043814.
    1. Miller-Kasprzak E, Jagodzinski PP. Endothelial progenitor cells as a new agent contributing to vascular repair. Arch Immunol Ther Exp (Warsz) 2007;55:247–259. doi: 10.1007/s00005-007-0027-5.
    1. Stamm C, Westphal B, Kleine HD, Petzsch M, Kittner C, Klinge H, Schümichen C, Nienaber CA, Freund M, Steinhoff G. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet. 2003;361:45–46. doi: 10.1016/S0140-6736(03)12110-1.
    1. Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Mesquita CT, Rossi MI, Carvalho AC, Dutra HS, Dohmann HJ, Silva GV, Belém L, Vivacqua R, Rangel FO, Esporcatte R, Geng YJ, Vaughn WK, Assad JA, Mesquita ET, Willerson JT. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation. 2003;107:2294–2302. doi: 10.1161/01.CIR.0000070596.30552.8B.
    1. Cashen AF, Lazarus HM, Devine SM. Mobilizing stem cells from normal donors: is it possible to improve upon G-CSF? Bone Marrow Transplant. 2007;39:577–588. doi: 10.1038/sj.bmt.1705616.
    1. Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N, Grünwald F, Aicher A, Urbich C, Martin H, Hoelzer D, Dimmeler S, Zeiher AM. Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI) Circulation. 2002;106:3009–3017. doi: 10.1161/.
    1. Valina C, Pinkernell K, Song YH, Bai X, Sadat S, Campeau RJ, Le Jemtel TH, Alt E. Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction. Eur Heart J. 2007;28:2667–2677. doi: 10.1093/eurheartj/ehm426.
    1. Bahlmann FH, de Groot K, Spandau JM, Landry AL, Hertel B, Duckert T, Boehm SM, Menne J, Haller H, Fliser D. Erythropoietin regulates endothelial progenitor cells. Blood. 2004;103:921–926. doi: 10.1182/blood-2003-04-1284.
    1. Westenbrink BD, Lipsic E, Meer P van der, Harst P van der, Oeseburg H, Du Marchie Sarvaas GJ, Koster J, Voors AA, van Veldhuisen DJ, van Gilst WH, Schoemaker RG. Erythropoietin improves cardiac function through endothelial progenitor cell and vascular endothelial growth factor mediated neovascularization. Eur Heart J. 2007;28:2018–2027. doi: 10.1093/eurheartj/ehm177.
    1. 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;3:205–221. doi: 10.1089/15270290260131939.
    1. Levine BD. Intermittent Hypoxic Training: Fact and Fancy. High Alt Med Biol. 2002;3:177–193. doi: 10.1089/15270290260131911.
    1. Levine BD, Stray-Gundersen J. "Living high-training low": effect of moderate-altitude acclimatization with low-altitude training on performance. J Appl Physiol. 1997;83:102–112.
    1. Koutedakis Y, Frischknecht R, Vrbova G, Sharp NC, Budgett R. Maximal voluntary quadriceps strength patterns in Olympic overtrained athletes. Med Sci Sports Exerc. 1995;27:566–572.
    1. Crameri RM, Weston A, Climstein M, Davis GM, Sutton JR. Effects of electrical stimulation-induced leg training on skeletal muscle adaptability in spinal cord injury. Scand J Med Sci Sports. 2002;12:316–322. doi: 10.1034/j.1600-0838.2002.20106.x.
    1. Brocherie F, Babault N, Cometti G, Maffiuletti N, Chatard JC. Electrostimulation training effects on the physical performance of ice hockey players. Med Sci Sports Exerc. 2005;37:455–460. doi: 10.1249/01.MSS.0000155396.51293.9F.
    1. Panisello P, Torrella JR, Pages T, Viscor G. Capillary Supply and Fiber Morphometry in Rat Myocardium after Intermittent Exposure to Hypobaric Hypoxia. High Alt Med Biol. 2007;8:322–330. doi: 10.1089/ham.2007.1030.
    1. Panisello P, Torrella JR, Esteva S, Pages T, Viscor G. 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;103:203–213. doi: 10.1007/s00421-008-0691-0.
    1. Rodriguez FA, Ventura JL, Casas M, Casas H, Pages T, Rama R, Ricart A, Palacios L, Viscor G. Erythropoietin acute reaction and haematological adaptations to short, intermittent hypobaric hypoxia. Eur J Appl Physiol. 2000;82:170–177. doi: 10.1007/s004210050669.
    1. Bennie SD, Petrofsky JS, Nisperos J, Tsurudome M, Laymon M. Toward the optimal waveform for electrical stimulation of human muscle. Eur J Appl Physiol. 2002;88:13–19. doi: 10.1007/s00421-002-0711-4.
    1. Keeney M, Chin-Yee I, Weir K, Popma J, Nayar R, Sutherland DR. 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. doi: 10.1002/(SICI)1097-0320(19980415)34:2<61::AID-CYTO1>;2-F.
    1. Valgimigli M, Rigolin GM, Cittanti C, Malagutti P, Curello S, Percoco G, Bugli AM, Della Porta M, Bragotti LZ, Ansani L, Mauro E, Lanfranchi A, Giganti M, Feggi L, Castoldi G, Ferrari R. 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;26:1838–1845. doi: 10.1093/eurheartj/ehi289.
    1. Falanga A, Marchetti M, Evangelista V, Manarini S, Oldani E, Giovanelli S, Galbusera M, Cerletti C, Barbui T. Neutrophil activation and hemostatic changes in healthy donors receiving granulocyte colony-stimulating factor. Blood. 1999;93:2506–2514.
    1. Gutierrez-Delgado F, Bensinger W. Safety of granulocyte colony-stimulating factor in normal donors. Curr Opin Hematol. 2001;8:155–160. doi: 10.1097/00062752-200105000-00005.
    1. Shintani S, Murohara T, Ikeda H, Ueno T, Honma T, Katoh A, Sasaki K, Shimada T, Oike Y, Imaizumi T. Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation. 2001;103:2776–2779. doi: 10.1161/hc2301.092122.
    1. Adams V, Lenk K, Linke A, Lenz D, Erbs S, Sandri M, Tarnok A, Gielen S, Emmrich F, Schuler G, Hambrecht R. Increase of circulating endothelial progenitor cells in patients with coronary artery disease after exercise-induced ischemia. Arterioscler Thromb Vasc Biol. 2004;24:684–690. doi: 10.1161/01.ATV.0000124104.23702.a0.
    1. Laufs U, Urhausen A, Werner N, Scharhag J, Heitz A, Kissner G, Böhm M, Kindermann W, Nickenig G. Running exercise of different duration and intensity: effect on endothelial progenitor cells in healthy subjects. Eur J Cardiovasc Prev Rehabil. 2005;12:407–414. doi: 10.1097/01.hjr.0000174823.87269.2e.
    1. 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;17:91–99. doi: 10.1080/13645700801969816.

Source: PubMed

3
Se inscrever