The effect of vascular complications of diabetes mellitus on human umbilical cord tissue and the number of Wharton Jelly’s mesenchymal stem cells


The current study investigated the change in umbilical cord tissue and the number of markers of Wharton’s jelly mesenchymal stem cells (WJ-MSC) in pregnant women with gestational diabetes (GDM), with chronic diabetes who developed nephropathy as vascular complication (VC-PGDM), and healthy pregnant women as the control. The umbilical cords (UC) were investigated by the histomorphological method and the number of WJ-MSC were detected by flow-cytometry using the CD90, CD44, CD105, and CD73 markers in Wharton’s jelly (WJ) isolated from fresh umbilical cords. The number of positive cells for CD 90, CD44, CD105, and CD73 were found to be elevated in the GDM group, whereas it was significantly diminished in the VC-PGDM group (p = 0.001, p = 0.001, p = 0.001, and p = 0.001). The only histopathological sign in the GDM group were an increased number of pores in the Wharton jelly. Artery wall thickness/cord diamater ratio was increased, which indicates an increase of the artery wall thickness in the VC- PGDM group (p = 0.039 and p = 0.048). The increase in umbilical cord diameter and number of Wharton jelly mesenchymal stem cells in babies of gestational diabetic mothers was considered as an effect of macrosomia seen in babies of mothers with gestational diabetes. Vasculopathy, a long-term complication of diabetes, is known to affect all tissues by causing marked lower perfusion and hypoxia, as well as a decrease in the MSC number in our study.

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  1. 1.

    White P (1978) Classification of obstetric diabetes. Am J Obstet Gynecol 130(2):228–230

    CAS  Article  Google Scholar 

  2. 2.

    Mayhew T (2002) Enhanced fetoplacental angiogenesis in pre-gestational diabetes mellitus: the extra growth is exclusively longitudinal and not accompanied by microvascular remodelling. Diabetologia 45(10):1434–1439

    CAS  Article  Google Scholar 

  3. 3.

    Verma R, Mishra S, Kaul JM (2010) Cellular changes in the placenta in pregnancies complicated with diabetes. Int J Morphol 28(1):259–264

    Article  Google Scholar 

  4. 4.

    Haeri S, Khoury J, Kovilam O, Miodovnik M (2008) The association of intrauterine growth abnormalities in women with type 1 diabetes mellitus complicated by vasculopathy. Am J Obstetr Gynecol 199(3):278. e1–278. e5.

  5. 5.

    Dunne FP (1999) Pregestational diabetes mellitus and pregnancy. Trends Endocrinol Metab 10(5):179–182

    CAS  Article  Google Scholar 

  6. 6.

    Arvas A (1993) Diyabetik Anne Bebeği. Perinatoloji Dergisi 1:122–127.

  7. 7.

    Bourbon JR, Farrell PM (1985) Fetal lung development in the diabetic pregnancy. Pediatr Res 19(3):253–267

    CAS  Article  Google Scholar 

  8. 8.

    Piazze JJ, Anceschi MM, Maranghi L, Brancato V, Marchiani E, Cosmi E (1999) Fetal lung maturity in pregnancies complicated by insulin-dependent and gestational diabetes: a matched cohort study. Eur J ObstetrGynecolReprod Biol 83(2):145–150

    CAS  Google Scholar 

  9. 9.

    Bongso A, Fong C-Y (2013) The therapeutic potential, challenges and future clinical directions of stem cells from the Wharton’s jelly of the human umbilical cord. Stem Cell Rev Rep 9(2):226–240

    CAS  Article  Google Scholar 

  10. 10.

    Wajid N, Nseem R, Anwar SS, Awan SJ, Ali M, Javed S (2015) The effect of gestational diabetes on proliferation capacity and viability of human umbilical cord-derived stromal cells. Cell Tissue Bank 16(3):389–397

    CAS  Article  Google Scholar 

  11. 11.

    Kim J, Piao Y, Pak Y et al (2015) Umbilical cord mesenchymal stromal cells affected by gestational diabetes mellitus display premature aging and mitochondrial dysfunction. Stem Cells Dev 24(5):575–586

    CAS  Article  Google Scholar 

  12. 12.

    Alam R, Momen A, Sultana AA, Hassan N (2014) Gross and Histomorphologic study of the umbilical cord in pre-gestational Diabetes mellitus and gestational Diabetes mellitus. Bangladesh J Anat 12(1):25–29

    Article  Google Scholar 

  13. 13.

    Ishibashi H, Suzuki T, Suzuki S et al (2003) Sex steroid hormone receptors in human thymoma. J Clin Endocrinol Metab 88(5):2309–2317

    CAS  Article  Google Scholar 

  14. 14.

    Schwartz R, Teramo KA (2000) Effects of diabetic pregnancy on the fetus and newborn. Semin Perinatol 24(2):120–135

    CAS  Article  Google Scholar 

  15. 15.

    Dilbaz S, Gelişen O, Dilbaz B et al (2004) Diabetik Gebeliklerde Diabet Tipinin Doğum Şekline, Doğum Ağirliğina Ve Apgar Skoruna Etkisi. Kadın Doğum Dergisi 2(4):275–277.

  16. 16.

    Arieh Riskin MAG-P (2020) Infants of women with diabetes. 2020 [cited 2020 10.04.202];

  17. 17.

    Ekici F, Yıldırım A, Sevim Ü et al (2010) Diyabetik anne bebeklerinin kardiyovasküler sistem hastalıkları ve izlemi. Gazi Med J 21(2):

  18. 18.

    Akarsu S, Çıtak Kurt N, Kurt A, Yımaz E, Aygün D (2008) Diyabetik anne bebeğinde klinik ve laboratuar bulguları. Fırat Tıp Dergisi 13(3):199–204.

  19. 19.

    Evers IM, de Valk HW, Visser GH (2004) Risk of complications of pregnancy in women with type 1 diabetes: nationwide prospective study in the Netherlands. BMJ 328(7445):915

    Article  Google Scholar 

  20. 20.

    Jensen DM, Damm P, Moelsted-Pedersen L et al (2004) Outcomes in type 1 diabetic pregnancies: a nationwide, population-based study. Diabetes Care 27(12):2819–2823

    Article  Google Scholar 

  21. 21.

    Saraç E (2015) Annelerinde Gestasyonel Diyabet Tanisi Olan Yenidoğanlarin Değerlendirilmeleri, in Pediatri. Dissertation. Abant İzzet Baysal Üniversitesi

  22. 22.

    Daskalakis G, Marinopoulos S, Krielesi V et al (2008) Placental pathology in women with gestational diabetes. Acta Obstetr Gynecol Scand 87(4):403–407

    Article  Google Scholar 

  23. 23.

    Taricco E, Radaelli T, Santis MS, Cetin I (2003) Foetal and placental weights in relation to maternal characteristics in gestational diabetes. Placenta 24(4):343–347

    CAS  Article  Google Scholar 

  24. 24.

    Binbir B, Yeniel A, Ergenoglu A et al (2012) The role of umbilical cord thickness and HbA1c levels for the prediction of fetal macrosomia in patients with gestational diabetes mellitus. Arch Gynecol Obstet 285(3):635–639

    CAS  Article  Google Scholar 

  25. 25.

    Kaya S (2015) Gestasyonel diyabet, preeklampsi, hellp sendromu ve normal gebelerde göbek kordonu histopatolojik değişiklikleri. Dissertation

  26. 26.

    Al-Kazzaz MM, Al-Hubaity A-JY (2000) Ultrastructural vascular changes of the human umbilical cord of new-born babies from diabetic mothers. Iraqi J Med Sci, p 37.

  27. 27.

    Weissman A, Jakobi P (1997) Sonographic measurements of the umbilical cord in pregnancies complicated by gestational diabetes. J Ultrasound Med 16(10):691–694

    CAS  Article  Google Scholar 

  28. 28.

    Blanco MV, Vega RH, Guerri-Guttenberg R et al (2011) Histopathology and histomorphometry of umbilical cord blood vessels. Findings in normal and high risk pregnancies. Artery Res 5(2):50–57

    Article  Google Scholar 

  29. 29.

    Pierdomenico L, Lanuti P, Lachmann R et al (2011) Diabetes mellitus during pregnancy interferes with the biological characteristics of Wharton’s Jelly mesenchymal stem cells. Open Tissue Eng Regener Med J 4(1):103

    Article  Google Scholar 

  30. 30.

    Montanucci P, Teresa P, Ilaria P et al (2018) Functional profiles of human umbilical cord-derived adult mesenchymal stem cells in obese/diabetic versus healthy women. Curr Diabetes Rev14(1):24–35.

  31. 31.

    Allen DA, Yaqoob MM, Harwood SM (2005) Mechanisms of high glucose-induced apoptosis and its relationship to diabetic complications. J Nutr Biochem 16(12):705–713

    CAS  Article  Google Scholar 

  32. 32.

    Afroze SH, Kalagiri RR, Reyes M et al (2016) Apoptotic and stress signaling markers are augmented in preeclamptic placenta and umbilical cord. BBA Clin 6:25–30

    Article  Google Scholar 

  33. 33.

    Belkacemi L, Kjos S, Nelson DM, Desai M, Ross MG (2013) Reduced apoptosis in term placentas from gestational diabetic pregnancies. J Dev Origins Health Dis 4(3):256–265

    CAS  Article  Google Scholar 

  34. 34.

    Fijany A, Sayadi RL, Khoshab N et al (2019) Mesenchymal stem cell dysfunction in diabetes. Mol Biol Rep 46(1):1459–1475

    CAS  Article  Google Scholar 

  35. 35.

    Kong C-M, Subramanian A, Biswas A et al (2019) Changes in stemness properties, differentiation potential, oxidative stress, senescence and mitochondrial function in Wharton’s Jelly stem cells of umbilical cords of mothers with gestational diabetes mellitus. Stem Cell Reviews and Reports 15(3):415–426

    CAS  Article  Google Scholar 

  36. 36.

    Athapathu H, Jayawardana M, Senanayaka L (2003) A study of the incidence of apoptosis in the human placental cells in the last weeks of pregnancy. J Obstet Gynaecol 23(5):515–517

    CAS  Article  Google Scholar 

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This study was funded by Gaziantep University Scientific Research Projects with project number TF.UT.18.04.

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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Çiğdem Karaca, Nuray Bostancıeri, Ali Ovayolu and Demet Taşdemir Karahan. The first draft of the manuscript was written by Çiğdem Karaca and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Cigdem Karaca.

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Permission was obtained with the decision of Gaziantep University Faculty of Medicine Medical Ethics Committee dated 24.07.2017 and numbered 2017/268. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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Karaca, C., Bostancıeri, N., Ovayolu, A. et al. The effect of vascular complications of diabetes mellitus on human umbilical cord tissue and the number of Wharton Jelly’s mesenchymal stem cells. Mol Biol Rep (2020).

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  • Umbilical cord
  • Vascular complication of diabetes