Potential Effects of Human Bone Marrow Non- Mesenchymal Mononuclear Cells on Neuronal Differentiation
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.
[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.
[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.
@article{"International Journal of Medical, Medicine and Health Sciences:55457", author = "Chareerut Phruksaniyom and Khwanthana Grataitong and Permphan Dharmasaroja and Surapol Issaragrisil", title = "Potential Effects of Human Bone Marrow Non- Mesenchymal Mononuclear Cells on Neuronal Differentiation", abstract = "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", volume = "5", number = "12", pages = "664-5", }