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Gestational Diabetes Affects the Growth and Functions of Perivascular Stem Cells

  • An, Borim (Department of Internal Medicine, School of Medicine, Kangwon National University) ;
  • Kim, Eunbi (Department of Internal Medicine, School of Medicine, Kangwon National University) ;
  • Song, Haengseok (Department of Biomedical Science, College of Life Science, CHA University) ;
  • Ha, Kwon-Soo (Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University) ;
  • Han, Eun-Taek (Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University) ;
  • Park, Won Sun (Department of Physiology, School of Medicine, Kangwon National University) ;
  • Ahn, Tae Gyu (Department of Obstetrics & Gynecology, School of Medicine, Kangwon National University) ;
  • Yang, Se-Ran (Department of Thoracic & Cardiovascular Surgery, School of Medicine, Kangwon National University) ;
  • Na, Sunghun (Department of Obstetrics & Gynecology, School of Medicine, Kangwon National University) ;
  • Hong, Seok-Ho (Department of Internal Medicine, School of Medicine, Kangwon National University)
  • Received : 2017.03.31
  • Accepted : 2017.05.11
  • Published : 2017.06.30

Abstract

Gestational diabetes mellitus (GDM), one of the common metabolic disorders of pregnancy, leads to functional alterations in various cells including stem cells as well as some abnormalities in fetal development. Perivascular stem cells (PVCs) have gained more attention in recent years, for the treatment of various diseases. However, the effect of GDM on PVC function has not been investigated. In our study, we isolated PVCs from umbilical cord of normal pregnant women and GDM patients and compared their phenotypes and function. There is no significant difference in phenotypic expression, response to bFGF exposure and adipogenic differentiation capacity between normal (N)-PVCs and GDM-PVCs. However, when compared with N-PVCs, early passage GDM-PVCs displayed decreased initial rates of cell yield and proliferation as well as a reduced ability to promote wound closure. These results suggest that maternal metabolic dysregulation during gestation can alter the function of endogenous multipotent stem cells, which may impact their therapeutic effectiveness.

Keywords

differentiation;gestational diabetes mellitus;perivascular stem cells;proliferation

Acknowledgement

Supported by : Ministry of Science, ICT and Future Planning

References

  1. Acosta, J.C., Haas, D.M., Saha, C.K., Dimeglio, L.A., Ingram, D.A., and Haneline, L.S. (2011). Gestational diabetes mellitus alters maternal and neonatal circulating endothelial progenitor cell subsets. Am. J. Obstet. Gynecol. 204, 254.e8-254 e15. https://doi.org/10.1016/j.ajog.2010.10.913
  2. An, B., Heo, H.R., Lee, S., Park, J.A., Kim, K.S., Yang, J., and Hong, S.H. (2015). Supplementation of growth differentiation factor-5 increases proliferation and size of chondrogenic pellets of human umbilical cord-derived perivascular stem cells. Tissue Eng. Regen. Med. 12, 181-187. https://doi.org/10.1007/s13770-015-0113-4
  3. An, B., Na, S., Lee, S., Kim, W.J., Yang, S.R., Woo, H.M., Kook, S., Hong, Y., Song, H., and Hong, S.H. (2015). Non-enzymatic isolation followed by supplementation of basic fibroblast growth factor improves proliferation, clonogenic capacity and SSEA-4 expression of perivascular cells from human umbilical cord. Cell Tissue Res. 359, 767-777. https://doi.org/10.1007/s00441-014-2066-7
  4. Buchanan, T.A., Xiang, A.H., and Page, K.A. (2012). Gestational diabetes mellitus: risks and management during and after pregnancy. Nat. Rev. Endocrinol. 8, 639-649. https://doi.org/10.1038/nrendo.2012.96
  5. Buemi, M., Allegra, A., D'Anna, R., Coppolino, G., Crasci, E., Giordano, D., Loddo, S., Cucinotta, M., Musolino, C., and Teti, D. (2007). Concentration of circulating endothelial progenitor cells (EPC) in normal pregnancy and in pregnant women with diabetes and hypertension. Am. J. Obstet. Gynecol. 196, 68 e61-66.
  6. Eriksson, J., Franssila-Kallunki, A., Ekstrand, A., Saloranta, C., Widen, E., Schalin, C., and Groop, L. (1989). Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus. N Eng. J. Med. 321, 337-343. https://doi.org/10.1056/NEJM198908103210601
  7. Geissler, S., Textor, M., Kuhnisch, J., Konnig, D., Klein, O., Ode, A., Pfitzner, T., Adjaye, J., Kasper, G., and Duda, G.N. (2012) Functional comparison of chronological and in vitro aging: differential role of the cytoskeleton and mitochondria in mesenchymal stromal cells. PloS one 7, e52700. https://doi.org/10.1371/journal.pone.0052700
  8. Hadarits, O., Zoka, A., Barna, G., Al-Aissa, Z., Rosta, K., Rigo, J., Jr., Kautzky-Willer, A., Somogyi, A., and Firneisz, G. (2016). Increased proportion of hematopoietic stem and progenitor cell population in cord blood of neonates born to mothers with gestational diabetes mellitus. Stem Cells Deve. 25, 13-17. https://doi.org/10.1089/scd.2015.0203
  9. Hong, S.H., Maghen, L., Kenigsberg, S., Teichert, A.M., Rammeloo, A.W., Shlush, E., Szaraz, P., Pereira, S., Lulat, A., Xiao, R., et al. (2013). Ontogeny of human umbilical cord perivascular cells: molecular and fate potential changes during gestation. Stem Cells Dev. 22, 2425-2439. https://doi.org/10.1089/scd.2012.0552
  10. Huysman, E., and Mathieu, C. (2009). Diabetes and peripheral vascular disease. Acta Chir. Belg. 109, 587-594. https://doi.org/10.1080/00015458.2009.11680493
  11. Kim, J., Piao, Y., Pak, Y.K., Chung, D., Han, Y.M., Hong, J.S., Jun, E.J., Shim, J.Y., Choi, J., and Kim, C.J. (2015). Umbilical cord mesenchymal stromal cells affected by gestational diabetes mellitus display premature aging and mitochondrial dysfunction. Stem Cells Dev. 24, 575-586. https://doi.org/10.1089/scd.2014.0349
  12. Kim, J.M., Hong, K.S., Song, W.K., Bae, D., Hwang, I.K., Kim, J.S., and Chung, H.M. (2016). Perivascular progenitor cells derived from human embryonic stem cells exhibit functional characteristics of pericytes and improve the retinal vasculature in a rodent model of diabetic retinopathy. Stem Cells Transl. Med. 5, 1268-1276. https://doi.org/10.5966/sctm.2015-0342
  13. Klinkhammer, B.M., Kramann, R., Mallau, M., Makowska, A., van Roeyen, C.R., Rong, S., Buecher, E.B., Boor, P., Kovacova, K., Zok, S., et al. (2014). Mesenchymal stem cells from rats with chronic kidney disease exhibit premature senescence and loss of regenerative potential. PLoS One 9, e92115. https://doi.org/10.1371/journal.pone.0092115
  14. Kolluru, G.K., Bir, S.C., and Kevil, C.G. (2012). Endothelial dysfunction and diabetes: effects on angiogenesis, vascular remodeling, and wound healing. Int. J. Vasc. Med. 2012, 918267.
  15. Leddy, M.A., Power, M.L., and Schulkin, J. (2008) The impact of maternal obesity on maternal and fetal health. Rev. Obstet. Gynecol. 1, 170-178.
  16. Maghen, L., Shlush, E., Gat, I., Filice, M., Barretto, T., Jarvi, K., Lo, K., Gauthier-Fisher, A.S., and Librach, C.L. (2016). Human umbilical perivascular cells: a novel source of MSCs to support testicular niche regeneration. Reproduction pii: REP-16-0220. [Epub ahead of print]
  17. Manea, A., Manea, S.A., Todirita, A., Albulescu, I.C., Raicu, M., Sasson, S., and Simionescu, M. (2015). High-glucose-increased expression and activation of NADPH oxidase in human vascular smooth muscle cells is mediated by 4-hydroxynonenal-activated $PPAR{\alpha}\;and\;PPAR{\beta}/{\delta}$. Cell. Tissue Res. 361, 593-604. https://doi.org/10.1007/s00441-015-2120-0
  18. Mantovani, C., Raimondo, S., Haneef, M.S., Geuna, S., Terenghi, G., Shawcross, S.G., and Wiberg, M. (2012). Morphological, molecular and functional differences of adult bone marrow- and adiposederived stem cells isolated from rats of different ages. Exp. Cell Res. 318, 2034-2048. https://doi.org/10.1016/j.yexcr.2012.05.008
  19. Montemurro, T., Andriolo, G., Montelatici, E., Weissmann, G., Crisan, M., Colnaghi, M.R., Rebulla, P., Mosca, F., Peault, B., and Lazzari, L. (2011). Differentiation and migration properties of human foetal umbilical cord perivascular cells: potential for lung repair. J. Cell. Mol. Med. 15, 796-808. https://doi.org/10.1111/j.1582-4934.2010.01047.x
  20. Moon, H.E., Yoon, S.H., Hur, Y.S., Park, H.W., Ha, J.Y., Kim, K.H., Shim, J.H., Yoo, S.H., Son, J.H., Paek, S.L., et al. (2013). Mitochondrial dysfunction of immortalized human adipose tissuederived mesenchymal stromal cells from patients with Parkinson's disease. Exp. Neurobiol. 22, 283-300. https://doi.org/10.5607/en.2013.22.4.283
  21. Penno, G., Pucci, L., Lucchesi, D., Lencioni, C., Iorio, M.C., Vanacore, R., Storti, E., Resi, V., Di Cianni, G., and Del Prato, S. (2011). Circulating endothelial progenitor cells in women with gestational alterations of glucose tolerance. Diab. Vasc. Dis. Res. 8, 202-210. https://doi.org/10.1177/1479164111408938
  22. Tsang, W.P., Shu, Y., Kwok, P.L., Zhang, F., Lee, K.K., Tang, M.K., Li, G., Chan, K.M., Chan, W.Y., and Wan, C. (2013). CD146+ human umbilical cord perivascular cells maintain stemness under hypoxia and as a cell source for skeletal regeneration. PLoS One 8, e76153. https://doi.org/10.1371/journal.pone.0076153
  23. Wajid, N., Naseem, R., Anwar, S.S., Awan, S.J., Ali, M., Javed, S., and Ali, F. (2015). The effect of gestational diabetes on proliferation capacity and viability of human umbilical cord-derived stromal cells. Cell Tissue Bank. 16, 389-397. https://doi.org/10.1007/s10561-014-9483-4
  24. Xu, S., Evans, H., Buckle, C., De Veirman, K., Hu, J., Xu, D., Menu, E., De Becker, A., Vande Broek, I., Leleu, X., et al. (2012). Impaired osteogenic differentiation of mesenchymal stem cells derived from multiple myeloma patients is associated with a blockade in the deactivation of the Notch signaling pathway. Leukemia 26, 2546-2549. https://doi.org/10.1038/leu.2012.126
  25. Zebardast, N., Lickorish, D., and Davies, J.E. (2010). Human umbilical cord perivascular cells (HUCPVC): A mesenchymal cell source for dermal wound healing. Organogenesis 6, 197-203. https://doi.org/10.4161/org.6.4.12393