1Cardiovascular Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
2Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
3Division of Biotechnology, Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
4Division of Biotechnology, Department of Pathobiology, School of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
5Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Objective(s): Nowadays much effort is being invested in order to diagnose the mechanisms involved in neural differentiation. By clarifying this, making desired neural cells in vitro and applying them into diverse neurological disorders suffered from neural cell malfunctions could be a feasible choice. Thus, the present study assessed the capability of fetal brain extract (FBE) to induce rat bone marrow-derived mesenchymal stem cells (BM-MSCs) toward neural cells. Materials and Methods: For this purpose, BM-MSCs were collected from rats and cultured and their mesenchymal properties were confirmed. After exposure of the BM-MSCs to fetal brain extract, the cells were evaluated and harvested at days 3 and 7 after treatment. Results: The BM-MSCs that were exposed to FBE changed their appearance dramatically from spindle shape to cells with dendrite-like processes. Those neural like processes were absent in the control group. In addition, a neural specific marker, vimentin, was expressed significantly in the treatment group but not in the negative control group. Conclusion: This study presented the FBE as a natural neural differentiation agent, which probably has required factors for making neurons. In addition, vimentin overexpression was observed in the treated group which confirms neuron-like cell differentiation of BM-MSCs after induction.
1. Sas K, Párdutz Á, Toldi J, Vécse L. Dementia, stroke and migraine — Some common pathological mechanisms. J Neurol Sci 2010; 299:55-65.
2. Silva NA, Sousa N, Reis RL, Salgado AnJ. From basics to clinical: A comprehensive review on spinal cord injury. Prog Neurobiol 2014; 114:25-57.
3. Luarte A, Bátiz LF, Wyneken U, Lafourcade C. Potential therapies by stem cell-derived exosomes in CNS diseases: focusing on the neurogenic niche. Stem Cells Int 2016; 2016:5736059.
4. Karaoz E, Aksoy A, Ayhan S, Sarıboyacı AE, Kaymaz F, Kasap M. Characterization of mesenchymal stem cells from rat bone marrow: ultrastructural properties, differentiation potential and immunophenotypic markers. Histochem Cell Biol 2009; 132:533-546.
5. Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 2000; 61:364-370.
6. Aboody KS, Brown A, Rainov NG, Bower KA, Liu S, Yang W, et al. Neural stem cells display extensive tropism for pathology in adult brain: Evidence from intracranial gliomas. Proc Natl Acad Sci U S A 2000; 97:12846-12851.
7. Ha HY, Jang SH, Jung JW. The use of pluripotent stem cell for personalized cell therapies against neurological disorders. J Biomed Biotechnol 2011; 2011:520816.
8. Song CH, Honmou O, Ohsawa N, Nakamura K, Hamada H, Furuoka H, et al. Effect of transplantation of bone marrow-derived mesenchymal stem cells on mice infected with prions. J Virol 2009; 83:5918-5927.
9. Tondreau T, Dejeneffe M, Meuleman N, Stamatopoulos B, Delforge A, Martiat P, et al. Gene expression pattern of functional neuronal cells derived from human bone marrow mesenchymal stromal cells. BMC Genomics 2008; 9:166-166.
10. Yilmaz G, Alexander JS, Yilmaz CE, Granger DN. Induction of neuro-protective/regenerative genes in stem cells infiltrating post-ischemic brain tissue. Exp Transl Stroke Med 2010; 2:11.
11. Zavan B, Giorgi C, Bagnara G, Vindigni V, Abatangelo G, Cortivo R. Osteogenic and chondrogenic differentiation: comparison of human and rat bone marrow mesenchymal stem cells cultured into polymeric scaffolds. Eur J Histochem 2007; 51:1.
12. Foudah D, Redondo J, Caldara C, Carini F, Tredici G, Miloso M. Expression of neural markers by undifferentiated rat mesenchymal stem cells. J Biomed Biotechnol 2012; 2012:820821.
13. Wang X, Wu H, Xue G, Hou Y. Progesterone promotes neuronal differentiation of human umbilical cord mesenchymal stem cells in culture conditions that mimic the brain microenvironment. Neural Regen Res 2012; 7:1925.
14. Cruz Villagrán C, Amelse L, Neilsen N, Dunlap J, Dhar M. Differentiation of equine mesenchymal stromal cells into cells of neural lineage: potential for clinical applications. Stem Cells Int 2014; 2014:891518.
15. Rahmanifar F, Tamadon A, Mehrabani D, Zare S, Abasi S, Keshavarz S, et al. Histomorphometric evaluation of treatment of rat azoospermic seminiferous tubules by allotransplantation of bone marrow-derived mesenchymal stem cells. Iran J Basic Med Sci 2016; 19:653-661.
16. Khajehahmadi Z, Mehrabani D, Ashraf MJ, Rahmanifar F, Tanideh N, Tamadon A, et al. Healing effect of conditioned media from bone marrow-derived stem cells in thioacetamide-induced liver fibrosis of rat. J Med Sci 2016; 15:1-9.
17. Razeghian Jahromi I, Mehrabani D, Mohammadi A, Dianatpour M, Tamadon A, Zare S, et al. The effect of fetal rat brain extract on morphology of bone marrow-derived mesenchymal stem cells. Comp Clin Pathol 2016; 25:343-349.
18. Tondreau T, Lagneaux L, Dejeneffe M, Massy M, Mortier C, Delforge A, et al. Bone marrow–derived mesenchymal stem cells already express specific neural proteins before any differentiation. Differentiation 2004; 72:319-326.
19. Smajilagić A, Aljičević M, Redžić A, Filipović S, Lagumdžija A. Rat bone marrow stem cells isolation and culture as a bone formative experimental system. Bosn J Basic Med Sci 2013; 13:27-30.
20. Jamous M, Al-Zoubi A, Khabaz MN, Khaledi R, Al Khateeb M, Al-Zoubi Z. Purification of mouse bone marrow-derived stem cells promotes ex vivo neuronal differentiation. Cell Transplant 2010; 19:193-202.
21. Abouelfetouh A, Kondoh T, Ehara K, Kohmura E. Morphological differentiation of bone marrow stromal cells into neuron-like cells after co-culture with hippocampal slice. Brain Res 2004; 1029:114-119.
22. Kim BG, Hwang DH, Lee SI, Kim EJ, Kim SU. Stem cell-based cell therapy for spinal cord injury. Cell Transplant 2007; 16:355-364.
23. Qian DX, Zhang HT, Ma X, Jiang X-D, Xu RX. Comparison of the efficiencies of three neural induction protocols in human adipose stromal cells. Neurochem Res 2010; 35:572-579.
24. 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; 164:247-256.
25. Blondheim NR, Levy YS, Ben-Zur T, Burshtein A, Cherlow T, Kan I, et al. Human mesenchymal stem cells express neural genes, suggesting a neural predisposition. Stem Cells Dev 2006; 15:141-164.
26. Sagara JI, Makino N. Glutathione induces neuronal differentiation in rat bone marrow stromal cells. Neurochem Res 2008; 33:16-21.
28. Zhao M, Chen Y, Li X, Wang J, Tu Y, Sun H, et al. Effect of chemical microenvironment after traumatic brain injury on temperature-sensitive umbilical cord mesenchymal stem cells. Zhongguo Ying Yong Sheng Li Xue Za Zh 2015; 31:207-210.
29. Rezanejad Keshteli FZ, Parivar K, Joghatayi MT, Ali Beik H. Study of the differentiation of rat omentum stem cells to nerve cells using brain tissue extract of Wistar rats. Int J Mol Cell Biotechnol 2014; 2014:1-13.
30. Chudickova M, Bruza P, Zajicova A, Trosan P, Svobodova L, Javorkova E, et al. Targeted neural differentiation of murine mesenchymal stem cells by a protocol simulating the inflammatory site of neural injury. J Tissue Eng Regen Med 2015; doi:10.1002/term.2059.
31. Qin X, Han W, Yu Z. Neuronal-like differentiation of bone marrow-derived mesenchymal stem cells induced by striatal extracts from a rat model of Parkinson's disease. Neural Regen Res 2012; 7:2673-2680.
32. 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; 24:1841-1851.
33. Wislet-Gendebien S, Leprince P, Moonen G, Rogister B. Regulation of neural markers nestin and GFAP expression by cultivated bone marrow stromal cells. J Cell Sci 2003; 116:3295-3302.
34. Munoz-Sanjuan I, Brivanlou AH. Neural induction, the default model and embryonic stem cells. Nat Rev Neurosci 2002; 3:271-280.