Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 32128
Potential Effects of Human Bone Marrow Non- Mesenchymal Mononuclear Cells on Neuronal Differentiation

Authors: Chareerut Phruksaniyom, Khwanthana Grataitong, Permphan Dharmasaroja, Surapol Issaragrisil


Bone marrow-derived stem cells have been widely studied as an alternative source of stem cells. Mesenchymal stem cells (MSCs) were mostly investigated and studies showed MSCs can promote neurogenesis. Little is known about the non-mesenchymal mononuclear cell fraction, which contains both hematopoietic and nonhematopoietic cells, including monocytes and endothelial progenitor cells. This study focused on unfractionated bone marrow mononuclear cells (BMMCs), which remained 72 h after MSCs were adhered to the culture plates. We showed that BMMC-conditioned medium promoted morphological changes of human SH-SY5Y neuroblastoma cells from an epithelial-like phenotype towards a neuron-like phenotype as indicated by an increase in neurite outgrowth, like those observed in retinoic acid (RA)-treated cells. The result could be explained by the effects of trophic factors released from BMMCs, as shown in the RT-PCR results that BMMCs expressed nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF). Similar results on the cell proliferation rate were also observed between RA-treated cells and cells cultured in BMMC-conditioned medium, suggesting that cells creased proliferating and differentiated into a neuronal phenotype. Using real-time RT-PCR, a significantly increased expression of tyrosine hydroxylase (TH) mRNA in SHSY5Y cells indicated that BMMC-conditioned medium induced catecholaminergic identities in differentiated SH-SY5Y cells.

Keywords: bone marrow, neuronal differentiation, neurite outgrowth, trophic factor, tyrosine hydroxylase

Digital Object Identifier (DOI):

Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 1440


[1] P. Dharmasaroja, "Bone marrow-derived mesenchymal stem cells for the treatment of ischemic stroke," J. Clin. Neurosci., vol. 16, no. 1, pp. 12-20, Jan. 2009.
[2] M. Chopp, Y. Li, "Treatment of neural injury with marrow stromal cells," Lancet Neurol., vol. 16, no. 2, pp. 92-100, Jun. 2002.
[3] A. M. Parr, C. H. Tator, A. Keating, "Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury," Bone Marrow Transplant., vol. 40, no. 7, pp. 609-619, Oct. 2007.
[4] V. T. Ribeiro-Resende, P. M. Pimentel-Coelho, L.A. Mesentier-Louro, R. M. Mendez, J. P. Mello-Silva, M.C. Cabral-da-Silva, et al., "Trophic activity derived from bone marrow mononuclear cells increases peripheral nerve regeneration by acting on both neuronal and glial cell populations," Neurosci., vol. 159, no. 2, pp. 540-549, Mar. 2009.
[5] G. C. Kopen, D. J. Prockop, D. C. Phinney, "Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains," Proc. Natl. Acad. Sci. USA, vol. 96, no. 19, pp. 10711-10716, Sep. 1999.
[6] L. R. Zhao, W. M. Duan, M. Reyes, C. D. Keene, C. M. Verfaillie, W. C. Low, "Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats," Exp. Neurol., vol. 174, no. 1, pp. 11-20, Mar. 2002.
[7] P. Cuevas, F. Carceller, I. Garcia-Gomez, M. Yan, M. Dujovny, "Bone marrow stromal cell implantation for peripheral nerve repair," Neurol. Res., vol. 26, no. 2, pp. 230-232, Mar. 2004.
[8] M. F. Pittenger, A. M. Mackay, S. C. Beck, R. K. Jaiswal, R. Douglas, J. D. Mosca, et al., "Multilineage potential of adult human mesenchymal stem cells," Science, vol. 284, no. 5411, pp. 143-147, Apr. 1999.
[9] L. R. Zhao, H. H. Berra, W. M. Duan, S. Singhal, J. Mehta, A. V. Apkarian, et al., "Beneficial effects of hematopoietic growth factor therapy in chronic ischemic stroke in rats," Stroke, vol. 38, no. 10, pp. 2804-2811, Oct. 2007.
[10] T. Sobrino, O. Hurtado, M. A. Moro, M. Rodriguez-Yanez, M. Castellanos, D. Brea, et al., "The increase of circulating endothelial progenitor cells after acute ischemic stroke is associated with good outcome," Stroke, vol. 38, no. 10, pp. 2759-2764, Oct. 2007.
[11] M. C. Caroleo, N. Costa, P. Tirassa, L. Aloe, "Nerve growth factor produced by activated human monocytes/macrophages is severely affected by ethanol," Alcohol, vol. 34, no.2-3, pp. 107-114, Oct.-Nov. 2004.
[12] M. Kerschensteiner, E. Gallmeier, L. Behrens, V. V. Leal, T. Misgeld, W. E. Klinkert, et al., "Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation?," J. Exp. Med., vol. 189, no.5, pp. 865-870, Mar. 1999.
[13] A. I. Su, T. Wiltshire, S. Batalov, H. Lapp, K. A. Ching, D. Block, et al., "A gene atlas of the mouse and human protein-encoding transcriptomes," Proc. Natl. Acad. Sci. USA, vol. 101, no.16, pp. 6062- 6067, Apr. 2004.
[14] M. Miloso, D. Villa, M. Crimi, S. Galbiati, E. Donzelli, G. Nicolini, et al., "Retinoic acid-induced neuritogenesis of human neuroblastoma SHSY5Y cells is ERK independent and PKC dependent," J. Neurosci. Res., vol. 75, no. 2, pp. 241-252, Jan. 2004.
[15] M. Encinas, M. Iglesias, Y. Liu, H. Wang, A. Muhaisen, V. Cena, et al., "Sequential treatment of SH-SY5Y cells with retinoic acid and brainderived neurotrophic factor gives rise to fully differentiated, neurotrophic factor-dependent, human neuron-like cells," J. Neurochem., vol. 75, no. 3, pp. 991-1003, Sep. 2000.
[16] T. Kume, Y. Kawato, F. Osakada, Y. Izumi, H. Katsuki, T. Nakagawa, et al., "Dibutyryl cyclic AMP induces differentiation of human neuroblastoma SH-SY5Y cells into a noradrenergic phenotype," Neurosci. Lett., vol. 443, no. 3, pp. 199-203, Oct. 2008.
[17] U. Steidl, S. Bork, S. Schaub, O. Selbach, J. Seres, M. Aivado, et al., "Primary human CD34+ hematopoietic stem and progenitor cells express functionally active receptors of neuromediators," Blood, vol. 104, no. 1, pp. 81-88, Jul. 2004.
[18] A. Taguchi, T. Matsuyama, H. Moriwaki, T. Hayashi, K. Hayashida, K. Nagatsuka, et al., "Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model," J. Clin. Invest., vol. 114, no. 3, pp. 330-338, Aug. 2004.
[19] C. V. Borlongan, A. Evans, G. Yu, D. C. Hess, "Limitations of intravenous human bone marrow CD133+ cell grafts in stroke rats," Brain Res., vol. 1048, no. 1-2, pp. 116-122, Jun. 2005.
[20] E. Paczkowska, B. Larysz, R. Rzeuski, A. Karbicka, R. Jalowinski, Z. Kornacewicz-Jach, et al., "Human hematopoietic stem/progenitorenriched CD34(+) cells are mobilized into peripheral blood during stress related to ischemic stroke or acute myocardial infarction," Eur. J. Haematol., vol. 75, no. 6, pp. 461-467, Dec. 2005.