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Published in: Anatomical Science International 2/2010

01-06-2010 | Original Article

NT-3 gene modified Schwann cells promote TrkC gene modified mesenchymal stem cells to differentiate into neuron-like cells in vitro

Authors: Yan-Qing Zhang, Xiang Zeng, Liu-Min He, Ying Ding, Yan Li, Yuan-Shan Zeng

Published in: Anatomical Science International | Issue 2/2010

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Abstract

Reports of neuronal differentiation of bone marrow derived mesenchymal stem cells (MSCs) suggested the possibility that these cells could serve as a source of treatment for spinal cord injury. However, the percentages of neuron-like cells differentiated from the MSCs were relatively low both in vitro and in vivo. Here, we investigated whether co-culture of human neurotrophin-3 (NT-3) gene modified Schwann cells (SCs) and human NT-3 receptor tyrosine protein kinase C (TrkC) gene modified MSCs could increase differentiation of neuron-like cells from MSCs. It was shown that MSCs were significantly promoted to differentiate into neuron-like cells, as evidenced immunocytochemically by the expression of neuronal markers, including nestin, β-III-tubulin, MAP2 and PSD95, 7 days after co-culture. However, the expression of glial fibrillary acidic protein (GFAP)—an astrocyte marker in these cells—was not so obvious. These results demonstrate that the binding of overexpressed NT-3 in SCs and its receptor TrkC in MSCs can be considered to stimulate the increased rate of neuronal differentiation.
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Literature
go back to reference Abouelfetouh A, Kondoh T, Ehara K, Kohmura E (2004) Morphological differentiation of bone marrow stromal cells into neuron-like cells after co-culture with hippocampal slice. Brain Res 1029:114–119CrossRefPubMed Abouelfetouh A, Kondoh T, Ehara K, Kohmura E (2004) Morphological differentiation of bone marrow stromal cells into neuron-like cells after co-culture with hippocampal slice. Brain Res 1029:114–119CrossRefPubMed
go back to reference Axanchi R, Bernal G, Gupta R, Keirstead HS (2004) Combined demyelination plus Schwann cell transplantation therapy increases spread of cells and axonal regeneration following contusion injury. J Neurotrauma 21:775–788CrossRef Axanchi R, Bernal G, Gupta R, Keirstead HS (2004) Combined demyelination plus Schwann cell transplantation therapy increases spread of cells and axonal regeneration following contusion injury. J Neurotrauma 21:775–788CrossRef
go back to reference Blesch A, Lu P, Tuszynski MH (2002) Neurotrophic factors, gene therapy, and neural stem cells for spinal cord repair. Brain Res Bull 57:833–838CrossRefPubMed Blesch A, Lu P, Tuszynski MH (2002) Neurotrophic factors, gene therapy, and neural stem cells for spinal cord repair. Brain Res Bull 57:833–838CrossRefPubMed
go back to reference El-Husseini AE, Schnell E, Chetkorich DM, Nicoll RA, Bredt DS (2000) PSD-95 involvement in maturation of excitatory synapses. Science 290:1304–1368CrossRef El-Husseini AE, Schnell E, Chetkorich DM, Nicoll RA, Bredt DS (2000) PSD-95 involvement in maturation of excitatory synapses. Science 290:1304–1368CrossRef
go back to reference Hofstetter CP, Schwarz EJ, Hess D et al (2002) Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci USA 99:2199–2204CrossRefPubMed Hofstetter CP, Schwarz EJ, Hess D et al (2002) Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci USA 99:2199–2204CrossRefPubMed
go back to reference Jin K, Mao XO, Batteur S, Sun Y, Greenberg DA (2003) Induction of neuronal markers in bone marrow cells: differential effects of growth factors and patterns of intracellular expression. Exp Neurol 184:78–89CrossRefPubMed Jin K, Mao XO, Batteur S, Sun Y, Greenberg DA (2003) Induction of neuronal markers in bone marrow cells: differential effects of growth factors and patterns of intracellular expression. Exp Neurol 184:78–89CrossRefPubMed
go back to reference Jori FP, Napolitano MA, Melone MA et al (2005) Molecular pathways involved in neural in vitro differentiation of marrow stromal stem cells. J Cell Biochem 94:645–655CrossRefPubMed Jori FP, Napolitano MA, Melone MA et al (2005) Molecular pathways involved in neural in vitro differentiation of marrow stromal stem cells. J Cell Biochem 94:645–655CrossRefPubMed
go back to reference Klopotowska D, Strzadala L (2005) The role of TrkC receptor and neurotrophin-3 in the development and function of neural cells. Postepy Hig Med Dosw 59:517–522 Klopotowska D, Strzadala L (2005) The role of TrkC receptor and neurotrophin-3 in the development and function of neural cells. Postepy Hig Med Dosw 59:517–522
go back to reference Kopen GC, Prckop DJ, Phinney DG (1999) Marrow stromal cells migrate throughout forebrain and cerebellum and diffentiate into astrocytes after injection into neonatal mouse brain. Proc Natl Acad Sci USA 96:10711–10716CrossRefPubMed Kopen GC, Prckop DJ, Phinney DG (1999) Marrow stromal cells migrate throughout forebrain and cerebellum and diffentiate into astrocytes after injection into neonatal mouse brain. Proc Natl Acad Sci USA 96:10711–10716CrossRefPubMed
go back to reference Li Y, Chen J, Chen XG et al (2002) Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery. Neurology 59:514–523PubMed Li Y, Chen J, Chen XG et al (2002) Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery. Neurology 59:514–523PubMed
go back to reference Qian L, Saltzman WM (2004) Improving the expansion and neuronal differentiation of mesenchymal stem cells through culture surface modification. Biomaterials 25:1331–1337CrossRefPubMed Qian L, Saltzman WM (2004) Improving the expansion and neuronal differentiation of mesenchymal stem cells through culture surface modification. Biomaterials 25:1331–1337CrossRefPubMed
go back to reference Sanchez-Ramos J, Song S, Cardozo-Pelaez F (2000) Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 164:247–256CrossRefPubMed Sanchez-Ramos J, Song S, Cardozo-Pelaez F (2000) Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 164:247–256CrossRefPubMed
go back to reference Shetty AK, Turner DA (1998) In vitro survival and differentiation of neurons derived from epidermal growth factor-responsive postnatal hippocampal stem cells: inducing effects of brain-derived neurotrophic factor. J Neurobiol 35:395–425CrossRefPubMed Shetty AK, Turner DA (1998) In vitro survival and differentiation of neurons derived from epidermal growth factor-responsive postnatal hippocampal stem cells: inducing effects of brain-derived neurotrophic factor. J Neurobiol 35:395–425CrossRefPubMed
go back to reference Ullian EM, Harris BT, Wu A, Chan JR, Barres BA (2004) Schwann cells and astrocytes induce synapse formation by spinal motor neurons in culture. Mol Cell Neurosci 25:241–251CrossRefPubMed Ullian EM, Harris BT, Wu A, Chan JR, Barres BA (2004) Schwann cells and astrocytes induce synapse formation by spinal motor neurons in culture. Mol Cell Neurosci 25:241–251CrossRefPubMed
go back to reference Wang JM, Zeng YS, Liu RY, Wu LZ, Xue G, Huang WL, Xiong Y, Wang YH (2005) Construction of a recombinant adenovirus vector expression human neurotrophin-3 with biological activity (in Chinese). Acta Anat Sin 36:501–506 Wang JM, Zeng YS, Liu RY, Wu LZ, Xue G, Huang WL, Xiong Y, Wang YH (2005) Construction of a recombinant adenovirus vector expression human neurotrophin-3 with biological activity (in Chinese). Acta Anat Sin 36:501–506
go back to reference Wang JM, Zeng YS, Liu RY, Huang WL, Xiong Y, Wang YH, Chen SJ, Teng YD (2007) Recombinant adenovirus vector-mediated functional expression of neurotropin-3 receptor (TrkC) in neural stem cells. Exp Neurol 203:123–127CrossRefPubMed Wang JM, Zeng YS, Liu RY, Huang WL, Xiong Y, Wang YH, Chen SJ, Teng YD (2007) Recombinant adenovirus vector-mediated functional expression of neurotropin-3 receptor (TrkC) in neural stem cells. Exp Neurol 203:123–127CrossRefPubMed
go back to reference Wang TT, Tio M, Lee W, Beerheide W, Udolph G (2007) Neural differentiation of mesenchymal-like stem cells from cord blood is mediated by PKA. Biochem Biophys Res Commun 357:1021–1027CrossRefPubMed Wang TT, Tio M, Lee W, Beerheide W, Udolph G (2007) Neural differentiation of mesenchymal-like stem cells from cord blood is mediated by PKA. Biochem Biophys Res Commun 357:1021–1027CrossRefPubMed
go back to reference Woodbury D, Schwarz EJ, Prockop DJ, Black IB (2000) Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 61:364–370CrossRefPubMed Woodbury D, Schwarz EJ, Prockop DJ, Black IB (2000) Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 61:364–370CrossRefPubMed
go back to reference Woodbury D, Reynolds K, Black IB (2002) Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis. J Neurosci Res 69:908–917CrossRefPubMed Woodbury D, Reynolds K, Black IB (2002) Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis. J Neurosci Res 69:908–917CrossRefPubMed
go back to reference Wu J, Sun TS, Ren JX, Wang XZ (2008) Ex vivo non-viral vector-mediated neurotrophin-3 gene transfer to olfactory ensheathing glia: effects on axonal regeneration and functional recovery after implantation in rats with spinal cord injury. Neurosci Bull 24:57–65CrossRefPubMed Wu J, Sun TS, Ren JX, Wang XZ (2008) Ex vivo non-viral vector-mediated neurotrophin-3 gene transfer to olfactory ensheathing glia: effects on axonal regeneration and functional recovery after implantation in rats with spinal cord injury. Neurosci Bull 24:57–65CrossRefPubMed
go back to reference Xu XM, Chen A, Guénard V, Kleitman N, Bunge MB (1997) Bridging Schwann cell transplants promote axonal regeneration from both the rostral and caudal stumps of transected adult rat spinal cord. J Neurocytol 26:1–16CrossRefPubMed Xu XM, Chen A, Guénard V, Kleitman N, Bunge MB (1997) Bridging Schwann cell transplants promote axonal regeneration from both the rostral and caudal stumps of transected adult rat spinal cord. J Neurocytol 26:1–16CrossRefPubMed
go back to reference Yano S, Kuroda S, Lee JB et al (2005) In vivo fluorescence tracking of bone marrow stromal cells transplanted into a pneumatic injury model of rat spinal cord. J Neurotrauma 22:907–918CrossRefPubMed Yano S, Kuroda S, Lee JB et al (2005) In vivo fluorescence tracking of bone marrow stromal cells transplanted into a pneumatic injury model of rat spinal cord. J Neurotrauma 22:907–918CrossRefPubMed
go back to reference Zhang W, Zeng YS, Zhang XB, Wang JM, Zhang W, Chen SJ (2006) Combination of adenoviral vector-mediated neurotrophin-3 gene transfer and retinoic acid promotes adult bone marrow cells to differentiate into neuronal phenotypes. Neurosci Lett 408:98–103CrossRefPubMed Zhang W, Zeng YS, Zhang XB, Wang JM, Zhang W, Chen SJ (2006) Combination of adenoviral vector-mediated neurotrophin-3 gene transfer and retinoic acid promotes adult bone marrow cells to differentiate into neuronal phenotypes. Neurosci Lett 408:98–103CrossRefPubMed
go back to reference Zurita M, Vaquero J (2006) Bone marrow stromal cells can achieve cure of chronic paraplegic rats: functional and morphological outcome one year after transplantation. Neurosci Lett 402:51–56CrossRefPubMed Zurita M, Vaquero J (2006) Bone marrow stromal cells can achieve cure of chronic paraplegic rats: functional and morphological outcome one year after transplantation. Neurosci Lett 402:51–56CrossRefPubMed
go back to reference Zurita M, Vaquero J, Oya S, Miguel M (2005) Schwann cells induce neuronal differentiation of bone marrow stromal cells. Neuroreport 16:505–508CrossRefPubMed Zurita M, Vaquero J, Oya S, Miguel M (2005) Schwann cells induce neuronal differentiation of bone marrow stromal cells. Neuroreport 16:505–508CrossRefPubMed
go back to reference Zurita M, Vaquero J, Oya S, Bonilla C, Aguayo C (2007) Neurotrophic Schwann-cell factors induce neural differentiation of bone marrow stromal cells. Neuroreport 18:1713–1717CrossRefPubMed Zurita M, Vaquero J, Oya S, Bonilla C, Aguayo C (2007) Neurotrophic Schwann-cell factors induce neural differentiation of bone marrow stromal cells. Neuroreport 18:1713–1717CrossRefPubMed
go back to reference Zurita M, Bonilla C, Otero L, Aguayo C, Vaquero J (2008) Neural transdifferentiation of bone marrow stromal cells obtained by chemical agents is a short-time reversible phenomenon. Neurosci Res 60:275–280CrossRefPubMed Zurita M, Bonilla C, Otero L, Aguayo C, Vaquero J (2008) Neural transdifferentiation of bone marrow stromal cells obtained by chemical agents is a short-time reversible phenomenon. Neurosci Res 60:275–280CrossRefPubMed
Metadata
Title
NT-3 gene modified Schwann cells promote TrkC gene modified mesenchymal stem cells to differentiate into neuron-like cells in vitro
Authors
Yan-Qing Zhang
Xiang Zeng
Liu-Min He
Ying Ding
Yan Li
Yuan-Shan Zeng
Publication date
01-06-2010
Publisher
Springer Japan
Published in
Anatomical Science International / Issue 2/2010
Print ISSN: 1447-6959
Electronic ISSN: 1447-073X
DOI
https://doi.org/10.1007/s12565-009-0056-8

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