Transdifferentiation of human adipose-derived mesenchymal stem cells into oligodendrocyte progenitor cells
AbstractBackground: Stem cell-based therapy is a new method for the treatment of neurodegenerative diseases such as multiple sclerosis (MS). Human adipose-derived stem cells (hADSCs) are a kind of adult stem cells which have a higher frequency in the fat tissue and have the ability to differentiate into other cell types outside their lineage. Due to some serious adverse events of cell-based therapy such as tumorigenic potential, the aim of this study was to evaluate of hADSCs differentiation into oligodendrocytes as a valuable way for future cell transplantation.Methods: hADSC were isolated from lipoaspirate samples of human abdominal fat. After hADSC characterization via flow cytometry, the cells were induced to oligodendrocytes using a special differentiation medium. Finally, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), immunocytochemistry, and real-time polymerase chain reaction (RT-PCR) techniques were used for the evaluation of differentiated cells.Results: Flow cytometry indicated that hADSCs were CD105- and CD49-positive, but were negative for CD31 and CD45 markers. In addition, immunocytochemistry analysis revealed that a high percent of differentiated cells expressed oligodendrocyte progenitor cells markers [A2B5 and oligodendrocyte transcription factor (Olig2)] which were significantly higher than myelin basic protein (MBP) which is mature oligodendrocytes marker. Moreover, a very low percentage of differentiated cells expressed glial fibrillary acidic protein (GFAP) marker. Finally, real-time reverse transcription PCR analysis confirmed the results of immunocytochemistry.Conclusion: Since hADSCs have the potential to differentiate into multi-lineage cells and due to their additional characteristics such as immunomodulatory and neuroprotective properties, it seems that these cells may be an ideal cell source for oligodendrocytes differentiation.
2. Holloman JP, Ho CC, Hukki A, Huntley JL, Gallicano GI. The development of hematopoietic and mesenchymal stem cell transplantation as an effective treatment for multiple sclerosis. Am J Stem Cells 2013; 2(2): 95-107.
3. de Andres C, Aristimuno C, de Las H, V, Martinez-Gines ML, Bartolome M, Arroyo R, et al. Interferon beta-1a therapy enhances CD4+ regulatory T-cell function: An ex vivo and in vitro longitudinal study in relapsing-remitting multiple sclerosis. J Neuroimmunol 2007; 182(1-2): 204-11.
4. Haas J, Korporal M, Balint B, Fritzsching B, Schwarz A, Wildemann B. Glatiramer acetate improves regulatory T-cell function by expansion of naive CD4(+)CD25(+)FOXP3(+)CD31(+) T-cells in patients with multiple sclerosis. J Neuroimmunol 2009; 216(1-2): 113-7.
5. Ghasemi N, Razavi S, Mardani M, Esfandiari E, Salehi H, Zarkesh Esfahani SH. Transplantation of human adipose-derived stem cells enhances remyelination in lysolecithin-induced focal demyelination of rat spinal cord. Mol Biotechnol 2014; 56(5): 470-8.
6. Constantin G, Marconi S, Rossi B, Angiari S, Calderan L, Anghileri E, et al. Adipose-derived mesenchymal stem cells ameliorate chronic experimental autoimmune encephalomyelitis. Stem Cells 2009; 27(10): 2624-35.
7. Sadan O, Shemesh N, Cohen Y, Melamed E, Offen D. Adult neurotrophic factor-secreting stem cells: A potential novel therapy for neurodegenerative diseases. Isr Med Assoc J 2009; 11(4): 201-4.
8. Sharp J, Frame J, Siegenthaler M, Nistor G, Keirstead HS. Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants improve recovery after cervical spinal cord injury. Stem Cells 2010; 28(1): 152-63.
9. Bai L, Lennon DP, Eaton V, Maier K, Caplan AI, Miller SD, et al. Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia 2009; 57(11): 1192-203.
10. Amariglio N, Hirshberg A, Scheithauer BW, Cohen Y, Loewenthal R, Trakhtenbrot L, et al. Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Med 2009; 6(2): e1000029.
11. Askari N, Yaghoobi MM, Shamsara M, Esmaeili-Mahani S. Human dental pulp stem cells differentiate into oligodendrocyte progenitors using the expression of olig2 transcription factor. Cells Tissues Organs 2014; 200(2): 93-103.
12. Mikaeili Agah E, Parivar K, Joghataei MT. Therapeutic effect of transplanted human Wharton's jelly stem cell-derived oligodendrocyte progenitor cells (hWJ-MSC-derived OPCs) in an animal model of multiple sclerosis. Mol Neurobiol 2014; 49(2): 625-32.
13. 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(3): 381-7.
14. Trzaska KA, Kuzhikandathil EV, Rameshwar P. Specification of a dopaminergic phenotype from adult human mesenchymal stem cells. Stem Cells 2007; 25(11): 2797-808.
15. Leite C, Silva NT, Mendes S, Ribeiro A, de Faria JP, Lourenco T, et al. Differentiation of human umbilical cord matrix mesenchymal stem cells into neural-like progenitor cells and maturation into an oligodendroglial-like lineage. PLoS One 2014; 9(10): e111059.
16. Li HC, Stoicov C, Rogers AB, Houghton J. Stem cells and cancer: Evidence for bone marrow stem cells in epithelial cancers. World J Gastroenterol 2006; 12(3): 363-71.
17. Werbowetski-Ogilvie TE, Bosse M, Stewart M, Schnerch A, Ramos-Mejia V, Rouleau A, et al. Characterization of human embryonic stem cells with features of neoplastic progression. Nat Biotechnol 2009; 27(1): 91-7.
18. Herberts CA, Kwa MS, Hermsen HP. Risk factors in the development of stem cell therapy. J Transl Med 2011; 9: 29.
19. Ghasemi N. Therapeutic effects of adipose derived mesenchymal stem cells on remyelination process in inflammatory demyelinating diseases. Histol Histopathol 2015; 2: 1-8.
20. Ghasemi N, Razavi S. Transdifferentiation potential of adipose-derived stem cells into neural lineage and their application. Histol Histopathol 2014; 1: 1-5.
21. Razavi S, Ahmadi N, Kazemi M, Mardani M, Esfandiari E. Efficient
transdifferentiation of human adipose-derived stem cells into Schwann-like cells: A promise for treatment of demyelinating diseases. Adv Biomed Res 2012; 1: 12.
22. Dedeepiya VD, Rao YY, Jayakrishnan GA, Parthiban JK, Baskar S, Manjunath SR, et al. Index of cd34+ cells and mononuclear cells in the bone marrow of spinal cord injury patients of different age groups: A comparative analysis. Bone Marrow Res 2012; 2012: 787414.
23. Deasy BM, Lu A, Tebbets JC, Feduska JM, Schugar RC, Pollett JB, et al. A role for cell sex in stem cell-mediated skeletal muscle regeneration: Female cells have higher muscle regeneration efficiency. J Cell Biol 2007; 177(1): 73-86.
24. Ogawa R, Mizuno H, Watanabe A, Migita M, Hyakusoku H, Shimada T. Adipogenic differentiation by adipose-derived stem cells harvested from GFP transgenic mice-including relationship of sex differences. Biochem Biophys Res Commun 2004; 319(2): 511-7.
25. Zhou Q, Wang S, Anderson DJ. Identification of a novel family of oligodendrocyte lineage-specific basic helix-loop-helix transcription factors. Neuron 2000; 25(2): 331-43.
26. Takebayashi H, Yoshida S, Sugimori M,
Kosako H, Kominami R, Nakafuku M, et al. Dynamic expression of basic helix-loop-helix Olig family members: Implication of Olig2 in neuron and oligodendrocyte differentiation and identification of a new member, Olig3. Mech Dev 2000; 99(1-2): 143-8.
27. Terzic D, Maxon JR, Krevitt L, DiBartolomeo C, Goyal T, Low WC, et al. Directed differentiation of oligodendrocyte progenitor cells from mouse induced pluripotent stem cells. Cell Transplant 2016; 25(2): 411-24.
28. Pouya A, Satarian L, Kiani S, Javan M, Baharvand H. Human induced pluripotent stem cells differentiation into oligodendrocyte progenitors and transplantation in a rat model of optic chiasm demyelination. PLoS One 2011; 6(11): e27925.
29. Nazm Bojnordi M, Movahedin M, Tiraihi T, Javan M, Ghasemi HamidabadiH. Oligoprogenitor cells derived from spermatogonia stem cells improve remyelination in demyelination model. Mol Biotechnol 2014; 56(5): 387-93.
30. Ebrahimi-Barough S, Kouchesfahani HM, Ai J, Massumi M. Differentiation of human endometrial stromal cells into oligodendrocyte progenitor cells (OPCs). J Mol Neurosci 2013; 51(2): 265-73.