Please enter verification code
Two-Step Induction of Dopaminergic Neurone Differentiation of Leukapharesis-Derived Mesenchymal Stem Cells
American Journal of Bioscience and Bioengineering
Volume 3, Issue 4-1, July 2015, Pages: 7-17
Received: Apr. 9, 2015; Accepted: Apr. 9, 2015; Published: May 6, 2015
Views 5061      Downloads 218
Zeinab M. Ismail, Histology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
Menna M. Abdel-Dayem, Histology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
Nagla M. Salama, Histology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
Hala Gabr, Clinical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
Dalia I. Ismail, Histology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
Ahmed S. Abdelhafiz, Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo, Egypt
Shaimaa I. El-Jaafary, Neurology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
Article Tools
Follow on us
Background: Neurodegenerative diseases represent a great medical challenge with marked consequences on quality of life of the patients and their families. Parkinson's disease (PD) constitutes a relatively common neurodegenerative disorder characterized by defect in dopaminergic neurons. The regenerative effect of mesenchymal stem cells (MSCs) stimulated research into their effect in treatment of PD. Subjects and Methods: Leukapharesis-derived MSC were isolated from 10 leukapharesis products using plastic adherence. Isolated MSCs were passaged, and passage III cells were induced to dopaminergic neurones using two-step protocol applying sequentially nerve growth factor and addition of ascorbic acid. Neuronal induction was evaluated by immunostaining against neurofilament protein, while dopaminergic neurons induction was evaluated using immunostaining against tyrosine hydroxylase. Results and Conclusions: MSCs were isolated in a rate of 0.12%-0.15% of leukapharesis cells, with viability ranging from 70-96%. NF positivity was 15.38±3.84, while the percentage of cells stained for TH was 5.94±0.65.MSCs could be successfully induced to dopaminergic neuron-like cells in vitro.
Mesenchymal Stem Cells, Dopaminergic Neurons, Parkinon's Disease
To cite this article
Zeinab M. Ismail, Menna M. Abdel-Dayem, Nagla M. Salama, Hala Gabr, Dalia I. Ismail, Ahmed S. Abdelhafiz, Shaimaa I. El-Jaafary, Two-Step Induction of Dopaminergic Neurone Differentiation of Leukapharesis-Derived Mesenchymal Stem Cells, American Journal of Bioscience and Bioengineering. Special Issue: Stem Cells for Neuro-Regeneration: Where Do We Stand. Vol. 3, No. 4-1, 2015, pp. 7-17. doi: 10.11648/
Wirdefeldt K, Adami HO, Cole P, Trichopoulos D, Mandel (2011):J. Epidemiology and etiology of Parkinson’s disease: a review of the evidence. Eur J Epidemiol.;26 Suppl 1:S1–S58.
Chiu C, Yeh TH, Lai SC, Wu-Chou YH, Chen CH, Mochly-Rosen D, Huang YC, Chen YJ, Chen CL, Chang YM, Wang HL, Lu CS (2015); Neuroprotective effects of aldehyde dehydrogenase 2 activation in rotenone-induce cellular and animal models of parkinsonism. Exp Neurol 263:244-53.
Muangpaisan W, Mathews A, Hori H, Seidel D. (2011):A systematic review of the worldwide prevalence and incidence of Parkinson’s disease. J Med Assoc Thai.;94(6):749–755.
Gaulden J and Reiter JF (2008): Neur-ons and neur-offs regulators of neural induction in vertebrate embryos and embryonic stem cells. Hum Mol Genet;17(R1): R60-66.
Deierborg T, Soulet D, Roybon L, Hall V, and Brundin P (2008): “Emerging restorative treatments for Parkinson’s disease,” Progress in Neurobiology, vol. 85, no. 4, pp. 407–432.
Kitada M and Dezawa M (2012): Parkinson’s Disease andMesenchymal Stem Cells: Potential for Cell-Based Therapy. Parkinson’s Disease.Volume 2012, , Article ID 873706, 9 pages, 2012. doi:10.1155/2012/873706.
Wyse R.D, Dunbar G.L. Rossignol. (2014):Use of Genetically Modified Mesenchymal Stem Cells to Treat Neurodegenerative Diseases. J.Int. J. Mol. Sci., 15(2), 1719-1745.
Glavaski-Joksimovic A, Bohn MC (2013): Mesenchymal stem cell and neuroregeneration in Parkinson's disease. Exp Neurol 247:25-38.
Taran R, Mamidi MK, Singh G, Dutta S, Parhar IS, John JP, Bhonde R Pal R, Das AK (2014): In vitro and in vivo neurogenic potential of mesenchymal stem cells isolated from different sources. J Biosci 39(1):157-69.
Gabr H, Abd El-Fattah R, Ahmed D, Farhan M, Mousa S, (2011): Mesenchymal stem cells derived from bone marrow and leukapheresis show different putative subpopulations. Stem Cell Studie 1(1):e19.
E. Mezey, K. J. Chandross, G. Harta, R. A. Maki, and S. R. McKercher (2000). “Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow,” Science, vol. 290, no. 5497, pp. 1779–1782.
Tondreau T, Meuleman N, Delforge A, Dejeneffe M, Leroy R, Massy M, Mortier C, Bron D and Lagneaux L (2005): Mesenchymal stem cells derived from CD133-positive cells in mobilized peripheral blood and cord blood: proliferation, Oct4 expression, and plasticity. Stem Cells; 23: 1105-1112.
Waller CF, Bronchud M, Mair S and Challand R (2010): Comparison of the pharmacodynamic profiles of a biosimilar filgrastim and Amgen filgrastim: results from a randomized, phase I trial. Ann Hematol; 89(10): 971–978.
Sotiropolou PA, Perez SA, Salagianni M, Baxevanis CN and Papamichail M (2006): Characterization of the optimal culture conditions for clinical scale production of human mesenchymal stem cells. Stem Cells; 24(2): 462-71.
Yan J, Studer L and McKay RD (2001): Ascorbic acid increases the yield of dopaminergic neurons derived from basic fibroblast growth factor expanded mesencephalic precursors. J Neurochem; 76(1): 307-11.
Bagga V, Dunnett SB, Fricker-Gates RA (2008): Ascorbic Acid Increases the Number of Dopamine Neurons in Vitro and in Transplants to the 6-OHDA-Lesioned Rat Brain. Cell Transp. 17:763-773.
Bancroft JD and Cook HC (eds) (1994): Immuno-cytochemistry. In: Manual of Histological Techniques and their Diagnostic Applications. Churchill Livingstone, Edinburgh, London, Madrid, Melbourne, New York and Tokyo, p. 263-325.
Jin P, Wang E, Ren J, Childs R, Shin JW, Khuu H, Marincola FM and Stroncek DF (2008): Differentiation of two types of mobilized peripheral blood stem cells by microRNA and cDNA expression analysis. J Transl Med; 6: 39
Helmy KY, Patel SA, Silverio K, Pliner L and Rameshwar P (2010): Stem cells and regenerative medicine: accomplishments to date and future promise. Ther Deliv; 1(5): 693-705.
Hölig K, Kramer M, Kroschinsky F, Bornhäuser M, Mengling T, Schmidt AH, Rutt C and Ehninger G (2009): Safety and efficacy of hematopoietic stem cell collection from mobilized peripheral blood in unrelated volunteers: 12 years of single-center experience in 3928 donors. Blood; 114(18): 3757-63.
Woods I, Tawab-Amiri A, Byrne K, Sabatino M and Stroncek DF (2010): Pilot analysis of cytokines levels in stored granulocyte-colony-stimulating factor-mobilized peripheral blood stem cell concentrates.Transfusion; 50(9): 2011-5.
Quillen K, Byrne P, Yau YY and Leitman SF (2009): Ten-year follow-up of unrelated volunteer granulocyte donors who have received multiple cycles of granulocyte-colony-stimulating factor and dexamethasone. Transfusion; 49(3): 513-8.
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenback I, Marini F, Krause D, Deans R, Keating A, Prockop Dj, Horwitz E (2006): Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315-317.
Wexler SA, Donaldson C, Denning-Kendall P, Rice C, Bradley B and Hows JM (2003): Adult bone marrow is a rich source of human mesenchymal 'stem' cells but umbilical cord and mobilized adult blood are not. Br J Haematol; 121: 368–374.
Fox JM, Chamberlain G, Ashton BA and Middleton J (2007): Recent advances into the understanding of mesenchymal stem cell trafficking. Br J Haematol; 137(6): 491-502.
Lund TC, Tolar J and Orchard PJ (2008): Granulocyte colony-stimulating factor mobilized CFU-F can be found in the peripheral blood but has limited expansion potential. Haematologica; 93(6): 908-12.
Mannello F and Tonti GA (2007): Concise review: no breakthroughs for human mesenchymal and embryonic stem cell culture: conditioned medium, feeder layer, or feeder-free; medium with fetal calf serum, human serum, or enriched plasma; serum-free, serum replacement nonconditioned medium, or ad hoc formula? All that glitters is not gold! Stem Cells; 25(7): 1603-9.
Scuri M, Samsell L and Piedimonte G (2010): The role of neurotrophins in inflammation and allergy. Inflamm Allergy Drug Targets; 9(3): 173-80.
Rangasamy SB, Soderstrom K, Bakay RA and Kordower JH (2010): Neurotrophic factor therapy for Parkinson's disease. Prog Brain Res; 184: 237-64.
Volpicelli F, Consales C, Caiazzo M, Colucci-D’Amato L, Perrone-Capano C and di Porzio U (2004): Enhancement of dopaminergic differentiation in proliferating midbrain neuroblasts by sonic hedgehog and ascorbic acid. Neural plasticity; 11(1-2): 45-57.
Harrison FE and May JM (2009): Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2. Free Radic Biol Med; 46(6): 719-30.
Farkas LM, Dunker N, Roussa E, Unsicker K and Krieglstein K (2003): Transforming growth factor-beta(s) are essential for the development of midbrain dopaminergic neurons in-vitro and in-vivo. The Journal of Neuroscience; 23 (12): 5178-5186.
Jiang Y, Henderson D, Blackstad M, Chen A, Miller RF, and Verfaillie CM (2003): Neuroectodermal differentiation from mouse multipotent adult progenitor cells. PNAS; 100 (1): 11854–11860.
Correia AS, Anisimov SV, Li J-Y and Brundin P (2008): Growth factors and feeder cells promote differentiation of human embryonic stem cells into dopaminergic neurons: a novel role for fibroblast growth factor-20. Front Neurosci; 2(1): 26–34.
Trzaska KA, King CC, Li KY, Kuzhikandathil EV, Nowycky MC, Ye JH and Rameshwar P (2009): Brain Derived Neurotrophic Factor Facilitates Maturation of Mesenchymal Stem Cell-Derived Dopamine Progenitors to Functional Neurons. J Neurochem; 10(3):568-576.
Science Publishing Group
1 Rockefeller Plaza,
10th and 11th Floors,
New York, NY 10020
Tel: (001)347-983-5186