Remyelination improvement after neurotrophic factors secreting cells transplantation in rat spinal cord injury

Document Type : Original Article

Authors

Department of Anatomical Science, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Objective(s): Neurotrophic factors secreting cells (NTS-SCs) may be a superior cell source for cell-based therapy in neurodegenerative diseases. NTS-SCs are able to secrete some neurotrophic Such as nerve growth factor and glia-derived neurotrophic factor. Our primary aim was to assess transplantation of neurotrophic factor secreting cells derived from human adipose-derived stem cells (hADSCs) into the damaged spinal cord rats and determine the potential of these cells in remyelination.
Materials and Methods: To this end, 40 adult male Wistar rats were categorized into four groups including; control, lysolecithin (Lysophosphatidylcholines or LPC), vehicle, and NTS-SCs transplan-tation. Local demyelination was induced using LPC injection into the lateral column of spinal cord. Seven days after the lysolecithin lesion, the cells transplantation was performed. The ultrastructure of myelinated fibers was examined with a transmission electron microscope to determine the extent of myelin destruction and remyelinization 4 weeks post cell transplantation. Moreover, the presence of oligodendrocyte in the lesion of spinal cord was assessed by immunohistochemistry procedure.
Results: The results of current study indicated that in NTF-SCs transplantation group, the remyelination process and the mean of myelin sheath thickness as well as axonal diameters were significantly higher than other groups (P<0.001). Furthermore, immunohistochemistry analysis revealed that in NTF-SCs transplantation group more than 10 percent of transplanted cells were positive for specific markers of oligodendrocyte cells.
Conclusion: NTF-SCs transplantation represents a valuable option for cell-based therapy in the nervous tissue damages.

Keywords

References

1.Ng TK, Fortino VR, Pelaez D, Cheung HS. Progress of mesenchymal stem cell therapy for neural and retinal diseases. World J Stem Cells 2014; 6:111-119.
2.Yin F, Guo L, Meng CY, Liu YJ, Lu RF, Li P, et al. Transplantation of mesenchymal stem cells exerts anti-apoptotic effects in adult rats after spinal cord ischemia-reperfusion injury. Brain Res 2014; 1561:1-10.
3.Razavi S, Nazem G, Mardani M, Esfandiari E, Salehi H, Esfahani SH. Neurotrophic factors and their effects in the treatment of multiple sclerosis. Adv Biomed Res 2015; 4.
4.Urschel BA, Hulsebosch CE. Schwann cell-neuronal interactions in the rat involve nerve growth factor. J Compa Neurol 1990; 296:114-122.
5.Zhao T, Yan W, Xu K. Combined treatment with platelet-rich plasma and brain-derived neurotrophic factor-overexpressing bone marrow stromal cells supports axonal remyelination in a rat spinal cord hemi-section model. Cytotherapy 2013; 15:792-804.
6.Someya Y, Koda M, Dezawa M. Reduction of cystic cavity, promotion of axonal regeneration and sparing, and functional recovery with transplanted bone marrow stromal cell-derived Schwann cells after contusion injury to the adult rat spinal cord: laboratory investigation. J Neurosurg Spine 2008;9: 600-610.
7.Sen A, Lea-Currie YR, Sujkowska D. Adipogenic potential of human adipose derived stromal cells from multiple donors is heterogeneous. J Cell Biochem 2001; 81:312-319.
8.Razavi S, Mardani M, Kazemi M. Effect of leukemia inhibitory factor on the myelinogenic ability of Schwann-like cells induced from human adipose-derived stem cells. Cell Mol Neurobiol 2013; 33:283-289.
9.Decker L, Desmarquet-Trin-Dinh C, Taillebourg E, Ghislain J, Vallat JM, Charnay P. Peripheral myelin maintenance is a dynamic process requiring constant Krox20 expression. J Neurosci 2006; 26:9771-9779.
10.Wei X, Du Z, Zhao L. IFATS collection: The conditioned media of adipose stromal cells protect against hypoxia-ischemia-induced brain damage in neonatal rats. Stem Cells 2009; 27:478-88.
11.Jahn O, Tenzer S, Werner HB. Myelin proteomics: molecular anatomy of an insulating sheath. Mol Neurobiol 2009; 40:55-72.
12.Tang L, Lu X, Zhu R. Adipose-derived stem cells expressing the neurogenin-2 promote functional recovery after spinal cord injury in rat. Cell Mol Neurobiol 2016; 36: 657-67.
13.Hur JW, Cho TH, Park DH, Lee JB, Park JY, Chung YG. Intrathecal transplantation of autologous adipose-derived mesenchymal stem cells for treating spinal cord injury: A human trial. J Spinal Cord Med 2016 ; 39:655-664.
14.Razavi S, Razavi MR, Zarkesh Esfahani H, Kazemi M, Mostafavi FS. Comparing brain-derived neurotrophic factor and ciliary neurotrophic factor secretion of induced neurotrophic factor secreting cells from human adipose and bone marrow-derived stem cells. Dev Growth Differ 2013; 55:648-655.
15.Sadan O, Shemesh N, Cohen Y, Melamed E, Offen D. Adult neurotrophic factor-secreting stem cells: a potential novel therapy for neurodegenerative diseases. Israel Med Assoc J IMAJ 2009; 11:201-204.
16.Ghasemi N, Razavi S, Mardani M, Esfandiari E, Salehi H, Esfahani SH. Transplantation of human adipose-derived stem cells enhances remyelination in lysolecithin-induced focal demyelination of rat spinal cord. Mol Biotechnol 2014; 56:470-478.
17.Razavi S, Razavi MR, Kheirollahi-Kouhestani M, Mardani M, Mostafavi FS. Co-culture with neurotrophic factor secreting cells induced from adipose-derived stem cells: promotes neurogenic differentiation. Biochem Biophys Res Commun 2013; 440:381-387.
18.Razavi S, Razavi MR, Ahmadi N, Kazemi M. Estrogen treatment enhances neurogenic differentiation of human adipose derived stem cells in vitro. Iran J Basic Med Sci 2015; 18: 799-804.
19.Boido M, Niapour A, Salehi H. Combined treatment by Co transplantation of mesenchymal stem cells and neural progenitors with exercise and enriched environment housing in mouse spinal cord injury. Adv Stem Cells 2014; 22.
20.Karimi-Abdolrezaee S, Billakanti R. Reactive astrogliosis after spinal cord injury—beneficial and detrimental effects. Mol Neurobiol 2012; 46:251-264.
21.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.
22.Zurita M, Vaquero J. Bone marrow stromal cells can achieve cure of chronic paraplegic rats: functional and morphological outcome one year after transplantation. Neurosci Lett 2006; 402:51-56.
23.Kulbatski I, Mothe AJ, Keating A, Hakamata Y, Kobayashi E, Tator CH. Oligodendrocytes and radial glia derived from adult rat spinal cord progenitors: morphological and immunocytochemical charac-terization. J Histochem Cytochem 2007; 55:209-222.
24.Pisati F, Bossolasco P, Meregalli M. Induction of neurotrophin expression via human adult mesenchymal stem cells: implication for cell therapy in neurodegenerative diseases. Cell Transplant 2007; 16:41-55.
25.Wang H, Wang Y, Li D. VEGF inhibits the inflammation in spinal cord injury through activation of autophagy. Biochem Biophys Res Commun 2015; 464:453-458.
26. Abbaszadeh HA, Tiraihi T, Noori-Zadeh A, Delshad AR, Sadeghizade M, Taheri T. Human ciliary neurotrophic factor–overexpressing stable bone marrow stromal cells in the treatment of a rat model of traumatic spinal cord injury. Cytotherapy 2015; 17:912-921.
27. Kovalchuk Y, Holthoff K, Konnerth A. Neurotrophin action on a rapid timescale. Curr Neurobiol 2004;14:558-563.
28.Zhang H, Wu F, Kong X. Nerve growth factor improves functional recovery by inhibiting endoplasmic reticulum stress-induced neuronal apoptosis in rats with spinal cord injury. J Translat Med 2014;12:1.
29.Harvey AR, Lovett SJ, Majda BT, Yoon JH, Wheeler LP, Hodgetts SI. Neurotrophic factors for spinal cord repair: Which, where, how and when to apply, and for what period of time? Brain Res 2015; 1619:36-71.
30. Sadan O, Melamed E, Offen D. Intrastriatal transplantation of neurotrophic factor-secreting human mesenchymal stem cells improves motor function and extends survival in R6/2 transgenic mouse model for Huntington’s disease. PLOS Curr 2012; 4:e4f7f6dc013d4e.
31. Sadan O, Shemesh N, Barzilay R, Bahat-Stromza M, Melamed E, Cohen Y, et al. Migration of neurotrophic factors-secreting mesenchymal stem cells toward a quinolinic acid lesion as viewed by magnetic resonance imaging. Stem Cells 2008; 26:2542-2551.
Iranian Journal of Basic Medical Sciences
Volume 20, Issue 4
April 2017
Pages 392-398

Files

Share

How to cite

Statistics