Effects of Estrogen on the Expression of Neural Markers in Differentiated Adipose-Derived Stem Cells

Document Type : Original Article(s)

Authors

1 Professor, Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

3 PhD Student, Department of Genetics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Student of Medicine, School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Over the past decade, researchers have used the existing knowledge about pathways messaging protocols to successfully stimulate stem cells to generate neurons. Due to the ease of access to adipose tissue-obtained stem cells rather than other sources, whereas estrogen factor could be used to improve neural differentiation, antilogous transplantation of differentiated neurons would be widely used for certain degenerative neurological diseases such as Parkinson's disease and spinal cord injuries. The purpose of this study was to evaluate the effect of estrogen on expression of microtubule-associated protein-2 (MAP2), glial fibrillary acidic protein (GFAP) and Nestin markers.Methods: After the isolation of stem cells from adipose tissue, the neural induction was carried out through neurosphere construction; then, final differentiation of the cells was performed. Neurosphere-singed cell were transferred to neural induction medium (control group). In the estrogen-treated group, estrogen was added to the culture medium until the end of the day of distinction. Then, evaluation of the expression of neural markers, was performed using reverse transcription-polymerase chain reaction (RT-PCR) technique. In addition, MTT assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] was performed to assess cell viability.Findings: The mean expression of GFAP and Nestin markers were down regulated in treated group compared to controls (P < 0.05). The difference between the mean of MAP2 expression was not significant between the two groups. In addition, the difference between the mean of cell viability was not significant between two groups, too.Conclusion: In this study, we found that estrogen can decrease the expression of neuronal markers. However, to determine the effect of estrogen on neurogenic differentiation of stem cells, next studies should be done broader using other precise techniques.Keywords: Estrogen, Neurogenesis, Adipose-derived stem cell, Reverse transcription-polymerase chain reaction (RT-PCR)

Keywords

References

  1. Barami K, Hao HN, Lotoczky GA, Diaz FG, Lyman WD. Transplantation of human fetal brain cells into ischemic lesions of adult gerbil hippocampus. J Neurosurg 2001; 95(2): 308-15.
  2. Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation 1974; 17(4): 331-40.
  3. Noth U, Osyczka AM, Tuli R, Hickok NJ, Danielson KG, Tuan RS. Multilineage mesenchymal differentiation potential of human trabecular bone-derived cells. J Orthop Res 2002; 20(5): 1060-9.
  4. da Silva ML, Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci 2006; 119(Pt 11): 2204-13.
  5. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284(5411): 143-7.
  6. Sanchez-Ramos J, Song S, Cardozo-Pelaez F, Hazzi C, Stedeford T, Willing A, et al. Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 2000; 164(2): 247-56.
  7. Grove JE, Bruscia E, Krause DS. Plasticity of bone marrow-derived stem cells. Stem Cells 2004; 22(4): 487-500.
  8. Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, et al. Bone marrow as a potential source of hepatic oval cells. Science 1999; 284(5417): 1168-70.
  9. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002; 418(6893): 41-9.
  10. Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 2000; 61(4): 364-70.
  11. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002; 13(12): 4279-95.
  12. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 2001; 7(2): 211-28.
  13. Halvorsen YD, Bond A, Sen A, Franklin DM, Lea-Currie YR, Sujkowski D, et al. Thiazolidinediones and glucocorticoids synergistically induce differentiation of human adipose tissue stromal cells: biochemical, cellular, and molecular analysis. Metabolism 2001; 50(4): 407-13.
  14. Erickson GR, Gimble JM, Franklin DM, Rice HE, Awad H, Guilak F. Chondrogenic potential of adipose tissue-derived stromal cells in vitro and in vivo. Biochem Biophys Res Commun 2002; 290(2): 763-9.
  15. Woodbury D, Reynolds K, Black IB. Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis. J Neurosci Res 2002; 69(6): 908-17.
  16. Lu P, Blesch A, Tuszynski MH. Induction of bone marrow stromal cells to neurons: differentiation, transdifferentiation, or artifact? J Neurosci Res 2004; 77(2): 174-91.
  17. Croft AP, Przyborski SA. Formation of neurons by non-neural adult stem cells: potential mechanism implicates an artifact of growth in culture. Stem Cells 2006; 24(8): 1841-51.
  18. Dezawa M, Kanno H, Hoshino M, Cho H, Matsumoto N, Itokazu Y, et al. Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. J Clin Invest 2004; 113(12): 1701-10.
  19. Egusa H, Schweizer FE, Wang CC, Matsuka Y, Nishimura I. Neuronal differentiation of bone marrow-derived stromal stem cells involves suppression of discordant phenotypes through gene silencing. J Biol Chem 2005; 280(25): 23691-7.
  20. Jiang Y, Henderson D, Blackstad M, Chen A, Miller RF, Verfaillie CM. Neuroectodermal differentiation from mouse multipotent adult progenitor cells. Proc Natl Acad Sci U S A 2003; 100(Suppl 1): 11854-60.
  21. Garcia-Segura LM, Azcoitia I, DonCarlos LL. Neuroprotection by estradiol. Prog Neurobiol 2001; 63(1): 29-60.
  22. Garcia-Segura LM, Veiga S, Sierra A, Melcangi RC, Azcoitia I. Aromatase: a neuroprotective enzyme. Prog Neurobiol 2003; 71(1): 31-41.
  23. Saravia FE, Beauquis J, Revsin Y, Homo-Delarche F, de Kloet ER, de Nicola AF. Hippocampal neuropathology of diabetes mellitus is relieved by estrogen treatment. Cell Mol Neurobiol 2006; 26(4-6): 943-57.
  24. Brann DW, Dhandapani K, Wakade C, Mahesh VB, Khan MM. Neurotrophic and neuroprotective actions of estrogen: basic mechanisms and clinical implications. Steroids 2007; 72(5): 381-405.
  25. Suzuki S, Brown CM, Wise PM. Mechanisms of neuroprotection by estrogen. Endocrine 2006; 29(2): 209-15.
  26. Toran-Allerand CD. Minireview: A plethora of estrogen receptors in the brain: where will it end? Endocrinology 2004; 145(3): 1069-74.
  27. Lephart ED. A review of brain aromatase cytochrome P450. Brain Res Brain Res Rev 1996; 22(1): 1-26.
  28. Martinez-Cerdeno V, Noctor SC, Kriegstein AR. Estradiol stimulates progenitor cell division in the ventricular and subventricular zones of the embryonic neocortex. Eur J Neurosci 2006; 24(12): 3475-88.
  29. Jin K, Wang X, Xie L, Mao XO, Zhu W, Wang Y, et al. Evidence for stroke-induced neurogenesis in the human brain. Proc Natl Acad Sci U S A 2006; 103(35): 13198-202.
  30. Yague JG, Munoz A, de Monasterio-Schrader P, Defelipe J, Garcia-Segura LM, Azcoitia I. Aromatase expression in the human temporal cortex. Neuroscience 2006; 138(2): 389-401.
  31. Wiltrout C, Lang B, Yan Y, Dempsey RJ, Vemuganti R. Repairing brain after stroke: a review on post-ischemic neurogenesis. Neurochem Int 2007; 50(7-8): 1028-41.
  32. Leker RR, Soldner F, Velasco I, Gavin DK, Androutsellis-Theotokis A, McKay RD. Long-lasting regeneration after ischemia in the cerebral cortex. Stroke 2007; 38(1): 153-61.
  33. Suzuki S, Gerhold LM, Bottner M, Rau SW, Dela CC, Yang E, et al. Estradiol enhances neurogenesis following ischemic stroke through estrogen receptors alpha and beta. J Comp Neurol 2007; 500(6): 1064-75.
  34. Brannvall K, Korhonen L, Lindholm D. Estrogen-receptor-dependent regulation of neural stem cell proliferation and differentiation. Mol Cell Neurosci 2002; 21(3): 512-20.
  35. Ivanova T, Karolczak M, Beyer C. Estradiol stimulates GDNF expression in developing hypothalamic neurons. Endocrinology 2002; 143(8): 3175-8.
  36. Bimonte-Nelson HA, Nelson ME, Granholm AC. Progesterone counteracts estrogen-induced increases in neurotrophins in the aged female rat brain. Neuroreport 2004; 15(17): 2659-63.
  37. Paganini-Hill A, Henderson VW. Estrogen deficiency and risk of Alzheimer's disease in women. Am J Epidemiol 1994; 140(3): 256-61.
  38. Hurn PD, Macrae IM. Estrogen as a neuroprotectant in stroke. J Cereb Blood Flow Metab 2000; 20(4): 631-52.
  39. Lafferty FW, Fiske ME. Postmenopausal estrogen replacement: a long-term cohort study. Am J Med 1994; 97(1): 66-77.
  40. Kang JH, Lee CK, Kim JR, Yu SJ, Jo JH, Do BR, et al. Estrogen stimulates the neuronal differentiation of human umbilical cord blood mesenchymal stem cells (CD34-). Neuroreport 2007; 18(1): 35-8.
  41. Razavi S, Mardani M, Kazemi M, Esfandiari E, Narimani M, Esmaeili A, et al. Effect of leukemia inhibitory factor on the myelinogenic ability of Schwann-like cells induced from human adipose-derived stem cells. Cell Mol Neurobiol 2013; 33(2): 283-9.
  42. Wang JM, Johnston PB, Ball BG, Brinton RD. The neurosteroid allopregnanolone promotes proliferation of rodent and human neural progenitor cells and regulates cell-cycle gene and protein expression. J Neurosci 2005; 25(19): 4706-18.
  43. Okada A, Kai O. Effects of estradiol-17beta and bisphenol A administered chronically to mice throughout pregnancy and lactation on the male pups' reproductive system. Asian J Androl 2008; 10(2): 271-6.
  44. Sekiguchi H, Ii M, Jujo K, Thorne T, Ito A, Klyachko E, et al. Estradiol promotes neural stem cell differentiation into endothelial lineage and angiogenesis in injured peripheral nerve. Angiogenesis 2013; 16(1): 45-58.
Journal of Isfahan Medical School
Volume 33, Issue 345 - Serial Number 345
July and August 2015
Pages 1239-1249

Files

History

  • Receive Date: 11 March 2015
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics