DOI QR코드

DOI QR Code

Absence of Correlation between Changes in the Number of Endothelial Progenitor Cell Subsets

  • Attar, Armin (Department of Cardiovascular Medicine, School of Medicine, Shiraz University of Medical Sciences) ;
  • Aghasadeghi, Kamran (Department of Cardiovascular Medicine, School of Medicine, Shiraz University of Medical Sciences) ;
  • Parsanezhad, Mohammad Ebrahim (Department of OB-GYN, Division of Infertility and Reproductive Medicine, School of Medicine, Shiraz University of Medical Sciences) ;
  • Jahromi, Bahia Namavar (Perinatology Research Center, Infertility Reaserch Center, Department of OB-GYN, School of Medicine, Shiraz University of Medical Sciences) ;
  • Habibagahi, Mojtaba (Department of Immunology, School of Medicine, Shiraz University of Medical Sciences)
  • Received : 2014.10.31
  • Accepted : 2014.12.29
  • Published : 2015.07.30

Abstract

Background and Objectives: Previously, various methodologies were used to enumerate the endothelial progenitor cells (EPCs). We now know that these methodologies enumerate at least three different EPC subsets: circulating angiogenic cells (CACs), colony-forming unit endothelial cells (CFU-ECs), and endothelial colony-forming cells (ECFCs). It is not clear whether there is a correlation between changes in the number of these subsets. The aim of the current study is to find an answer to this question. Materials and Methods: The number of all EPC subsets was quantified in the peripheral blood of nine pregnant women in their first and third trimesters of pregnancy. We enumerated 14 cell populations by quantitative flow-cytometry using various combinations of the markers, CD34, CD133, CD309, and CD45, to cover most of the reported phenotypes of CACs and ECFCs. Culturing technique was used to enumerate the CFU-ECs. Changes in the number of cells were calculated by subtracting the number of cells in the first trimester peripheral blood from the number of cells in the third trimester peripheral blood, and correlations between these changes were analyzed. Results: The number of CFU-ECs did not correlate with the number of ECFCs and CACs. Also, CACs and ECFCs showed independent behaviors. However, the number of CACs showed a strong correlation with the number of $CD133^{+}CD309^{+}$ cells (p=0.001) and a moderate correlation with the number of $CD34^{+}CD309^{+}$ cells (p=0.042). Also, the number of ECFCs was correlated with the number of $CD309^{+}CD45^{-}$ cells (p=0.029) and $CD34^{+}CD45^{-}$ cells (p=0.03). Conclusion: Our study showed that the three commonly used methods for quantifying EPC subsets represent different cells with independent behaviors. Also, any study that measured the number of EPCs using the flow cytometry method with a marker combination that lacks CD309 may be inaccurate.

Keywords

Acknowledgement

Supported by : Shiraz University of Medical Sciences

References

  1. Attar A, Khosravi Maharlooi M, Khoshkhou S, et al. Colony forming unit endothelial cells do not exhibit telomerase alternative splicing variants and activity. Iran Biomed J 2013;17:146-51.
  2. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997;275:964-7. https://doi.org/10.1126/science.275.5302.964
  3. Hill JM, Zalos G, Halcox JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 2003;348:593-600. https://doi.org/10.1056/NEJMoa022287
  4. Lin C, Rajakumar A, Plymire DA, Verma V, Markovic N, Hubel CA. Maternal endothelial progenitor colony-forming units with macrophage characteristics are reduced in preeclampsia. Am J Hypertens 2009; 22:1014-9. https://doi.org/10.1038/ajh.2009.101
  5. Peichev M, Naiyer AJ, Pereira D, et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 2000;95:952-8.
  6. Werner N, Kosiol S, Schiegl T, et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 2005;353:999-1007. https://doi.org/10.1056/NEJMoa043814
  7. Timmermans F, Plum J, Yöder MC, Ingram DA, Vandekerckhove B, Case J. Endothelial progenitor cells: identity defined? J Cell Mol Med 2009;13:87-102.
  8. Guven H, Shepherd RM, Bach RG, Capoccia BJ, Link DC. The number of endothelial progenitor cell colonies in the blood is increased in patients with angiographically significant coronary artery disease. J Am Coll Cardiol 2006;48:1579-87.
  9. Allanore Y, Batteux F, Avouac J, Assous N, Weill B, Kahan A. Levels of circulating endothelial progenitor cells in systemic sclerosis. Clin Exp Rheumatol 2007;25:60-6.
  10. Schömig K, Busch G, Steppich B, et al. Interleukin-8 is associated with circulating CD133+ progenitor cells in acute myocardial infarction. Eur Heart J 2006;27:1032-7. https://doi.org/10.1093/eurheartj/ehi761
  11. Hirschi KK, Ingram DA, Yoder MC. Assessing identity, phenotype, and fate of endothelial progenitor cells. Arterioscler Thromb Vasc Biol 2008;28:1584-95. https://doi.org/10.1161/ATVBAHA.107.155960
  12. Ingram DA, Mead LE, Tanaka H, et al. Identifi cation of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood 2004;104:2752-60. https://doi.org/10.1182/blood-2004-04-1396
  13. Povsic TJ, Zavodni KL, Vainorius E, Kherani JF, Goldschmidt-Clermont PJ, Peterson ED. Common endothelial progenitor cell assays identify discrete endothelial progenitor cell populations. Am Heart J 2009;157:335-44. https://doi.org/10.1016/j.ahj.2008.10.010
  14. Tura O, Barclay GR, Roddie H, Davies J, Turner ML. Absence of a relationship between immunophenotypic and colony enumeration analysis of endothelial progenitor cells in clinical haematopoietic cell sources. J Transl Med 2007;5:37. https://doi.org/10.1186/1479-5876-5-37
  15. George J, Shmilovich H, Deutsch V, Miller H, Keren G, Roth A. Comparative analysis of methods for assessment of circulating endothelial progenitor cells. Tissue Eng 2006;12:331-5. https://doi.org/10.1089/ten.2006.12.331
  16. Parsanezhad ME, Attar A, Namavar-Jahromi B, et al. Changes in endothelial progenitor cell subsets in normal pregnancy compared with preeclampsia. J Chin Med Assoc 2015;78:345-52. https://doi.org/10.1016/j.jcma.2015.03.013
  17. Khan SS, Solomon MA, McCoy JP Jr. Detection of circulating endothelial cells and endothelial progenitor cells by flow cytometry. Cytometry B Clin Cytom 2005;64:1-8.
  18. Buemi M, Allegra A, D'Anna R, et al. Concentration of circulating endothelial progenitor cells (EPC) in normal pregnancy and in pregnant women with diabetes and hypertension. Am J Obstet Gynecol 2007;196:68.e1-6. https://doi.org/10.1016/j.ajog.2006.08.032
  19. Friedrich EB, Walenta K, Scharlau J, Nickenig G, Werner N. CD34-/CD133+/VEGFR-2+ endothelial progenitor cell subpopulation with potent vasoregenerative capacities. Circ Res 2006;98:e20-5. https://doi.org/10.1161/01.RES.0000205765.28940.93
  20. Heiss C, Keymel S, Niesler U, Ziemann J, Kelm M, Kalka C. Impaired progenitor cell activity in age-related endothelial dysfunction. J Am Coll Cardiol 2005;45:1441-8. https://doi.org/10.1016/j.jacc.2004.12.074
  21. Powell TM, Paul JD, Hill JM, et al. Granulocyte colony-stimulating factor mobilizes functional endothelial progenitor cells in patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2005;25:296-301.
  22. Massa M, Campanelli R, Bonetti E, Ferrario M, Marinoni B, Rosti V. Rapid and large increase of the frequency of circulating endothelial colony-forming cells (ECFCs) generating late outgrowth endothelial cells in patients with acute myocardial infarction. Exp Hematol 2009;37:8-9. https://doi.org/10.1016/j.exphem.2008.09.007
  23. Davani S, Gozalo C, Gambert S, et al. The polymorphism Trp719Arg in the kinesin-like protein 6 is associated with the presence of late outgrowth endothelial progenitor cells in acute myocardial infarction. Atherosclerosis 2010;210:48-50. https://doi.org/10.1016/j.atherosclerosis.2009.11.041

Cited by

  1. Endothelial progenitor cell subsets and preeclampsia: Findings and controversies vol.80, pp.10, 2015, https://doi.org/10.1016/j.jcma.2017.06.013
  2. Increased serum levels of fractalkine and mobilisation of CD34 + CD45 endothelial progenitor cells in systemic sclerosis vol.19, pp.None, 2015, https://doi.org/10.1186/s13075-017-1271-7
  3. Purification of Stem Cells from Oral Pyogenic Granuloma Tissue vol.12, pp.None, 2015, https://doi.org/10.2174/1874210601812010560
  4. Effects of metoprolol, methyldopa, and nifedipine on endothelial progenitor cells in patients with gestational hypertension and preeclampsia vol.46, pp.4, 2015, https://doi.org/10.1111/1440-1681.13063
  5. Reduced myocardial reserve in cirrhotic patients: an evaluation by dobutamine stress speckle tracking and tissue Doppler imaging (TDI) echocardiography vol.11, pp.2, 2015, https://doi.org/10.15171/jcvtr.2019.22
  6. Global longitudinal strain as an Indicator of cardiac Iron overload in thalassemia patients vol.17, pp.1, 2019, https://doi.org/10.1186/s12947-019-0174-y
  7. AICAR and nicotinamide treatment synergistically augment the proliferation and attenuate senescence-associated changes in mesenchymal stromal cells vol.11, pp.1, 2015, https://doi.org/10.1186/s13287-020-1565-6
  8. CD34+ cells and endothelial progenitor cell subpopulations are associated with cerebral small vessel disease burden vol.15, pp.3, 2015, https://doi.org/10.2217/bmm-2020-0350