Number and Potential of Endothelial Progenitor Cells in Controlled Group of Type 2 Diabetes Mellitus Patients are Higher than the Poorly Controlled Group

Siska Darmayanti, Rini Hendriani, Cynthia Retna Sartika


BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is a metabolic disease caused by the disorder of insulin function, insulin secretion or both. Long-term hyperglycemia conditions can lead to multiple organ dysfunctions with endothelial dysfunction. Endothelial dysfunction is a cardiovascular-associated risk with the changes in Endothelial Progenitor Cells (EPC). This condition causes an increase in Hematopoietic Stem Cell (HSC) apoptosis, so that the numbers of circulating HSC and EPC decrease. The purpose of this study was to determine the number and potential of EPC cells in T2DM patients as one of the risk factors for cardiovascular disease.

METHODS: Thirty-eight T2DM male patients were classified into two group based on Indonesian Society of Endocrinology/Perkumpulan Endokrinologi Indonesia (PERKENI) criteria on T2DM. The first group was a controlled glycemic condition (hemoglobin A1c (HbA1C) <7.0%) and the second group was a poorly controlled glycemic condition (HbA1C >7.0%). Cluster of differentiation (CD)34+ and CD133+ expressions showed the number of EPC, whereas quantified bright aldehyde dehydrogenase (ALDHbr) showed the cell potential.

RESULTS: This study showed that in the poorly controlled group of T2DM, there was a decrease of EPC number to 24.80% (p<0.05), compared to the controlled group. Similarly, the expression of ALDHbr representing the potential of EPC cells was found to be lower by 43.07% (p<0.05) in the poorly controlled group.

CONCLUSION: This study showed that the number and potential of EPC were decreasing in the poorly controlled T2DM group.

KEYWORDS: ALDHbr, endothelial progenitor cells, type 2 diabetes mellitus

Full Text:



American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010; 34 (Suppl 1): S62-9, CrossRef.

Indonesian Society of Endocrinology/Perkumpulan Endokrinologi Indonesia (PERKENI). Konsensus Pengelolaan dan pencegahan Diabetes melitus di Indonesia. Jakarta: PERKENI; 2015, article.

Mapanga R, Essop M. Damaging effects of hyperglycemia on cardiovascular function: spotlight on glucose metabolic pathways. Am J Physiol Heart Circ Physiol. 2016; 310: H153-73, CrossRef.

Fadini G, Sartore S, Agostini C, Avogaro A. Significance of endothelial progenitor cells in subjects with diabetes. Diabetes Care. 2007; 30: 1305-13, CrossRef.

Yoder M. Human endothelial progenitor cells. Cold Spring Harb Perspect Med. 2011; 2: a006692, CrossRef.

Chirayath H. An overview of endothelial dysfunction in diabetes. Vascul Dis Ther. 2016; 1: 1-3, CrossRef.

Issan Y, Hochhauser E, Kornowski R, Leshem-Lev D, Lev E, Sharoni R, et al. Endothelial progenitor cell function inversely correlates with long-term glucose control in diabetic patients: association with the attenuation of the heme oxygenase-adiponectin axis. Can J Cardiol. 2012; 28: 728-36, CrossRef.

Rajasekar P, O’Neill C, Eeles L, Stitt A, Medina R. Epigenetic changes in endothelial progenitors as a possible cellular basis for glycemic memory in diabetic vascular complications. J Diabetes Res. 2015; 2015: 436879, CrossRef.

Churdchomjan W, Kheolamai P, Manochantr S, Tapanadechopone P, Tantrawatpan C, U-pratya Y, et al. Comparison of endothelial progenitor cell function in type 2 diabetes with good and poor glycemic control. BMC Endocr Disord. 2010; 10: 5, CrossRef.

Szpera-Goździewicz A, Majcherek M, Boruczkowski M, Goździewicz T, Dworacki G, Wicherek L, et al. Circulating endothelial cells, circulating endothelial progenitor cells, and von Willebrand factor in pregnancies complicated by hypertensive disorders. Am Reprod Immunol. 2017; 77: e12625, CrossRef.

Balber AE. Aldehyde dehydrogenase bright stem and progenitor cell populations from normal tissues: characteristics, activities, and emerging uses in regenerative medicine. Stem Cells. 2011; 29: 570-5, CrossRef.

Imanishi T, Tsujioka H, Akasaka T. Endothelial progenitor cells dysfunction and senescence: contribution to oxidative stress. Curr Cardiol Rev. 2008; 4: 275-86, CrossRef.

Shao L, Li H, Pazhanisamy S, Meng A, Wang Y, Zhou D. Reactive oxygen species and hematopoietic stem cell senescence. Int J Hematol. 2011; 94: 24-32, CrossRef.

Chen F, Liu Y, Wong N, Xiao J, So K. Oxidative stress in stem cell aging. Cell Transplant. 2017; 26: 1483-95, CrossRef.

Alison M, Guppy N, Lim S, Nicholson L. Finding cancer stem cells: are aldehyde dehydrogenases fit for purpose?. J Pathol. 2010; 222: 335-44, CrossRef.

Shoulars K, Noldner P, Troy J, Cheatham L, Parrish A, Page K, et al. Development and validation of a rapid, aldehyde dehydrogenase bright-based cord blood potency assay. Blood. 2016; 127: 2346-54, CrossRef.

Prieto-Vila M, Takahashi R, Usuba W, Kohama I, Ochiya T. Drug resistance driven by cancer stem cells and their niche. Int J Mol Sci. 2017; 18: 2574, CrossRef.

White H, Smith L, Gentry T, Balber AE. Mechanisms of action of human aldehyde dehydrogenase bright cells in therapy of cardiovascular diseases: expression analysis of angiogenic factors and aldehyde dehydrogenase isozymes. J Stem Cell Res Ther. 2011; S1: 1-9, CrossRef.

Makino H, Miyamoto Y, Kikuchi-Taura A, Soma T, Taguchi A, Kishimoto I. Decreased levels of circulating CD34+ cells are associated with coronary heart disease in Japanese patients with type 2 diabetes. J Diabetes Invest. 2014; 6: 473-8, CrossRef.

Nowak W, Borys S, Kusińska K, Bukowska-Strakova K, Witek P, Koblik T, et al. Number of circulating pro-angiogenic cells, growth factor and anti-oxidative gene profiles might be altered in type 2 diabetes with and without diabetic foot syndrome. J Diabetes Invest. 2013; 5: 99-107, CrossRef.

Urbich C, Dimmeler S. Endothelial progenitor cells: characterization and role in vascular biology. Circ Res. 2004; 95: 343-53, PMID.


Indexed by:






The Prodia Education and Research Institute