Skip to main content
Top
Published in: Acta Neurochirurgica 7/2014

01-07-2014 | Experimental Research - Brain Injury

Transplantation of neurotrophin-3-expressing bone mesenchymal stem cells improves recovery in a rat model of spinal cord injury

Authors: Ling-Jie Wang, Rui-Ping Zhang, Jian-Ding Li

Published in: Acta Neurochirurgica | Issue 7/2014

Login to get access

Abstract

Background

This study aimed to investigate the therapeutic effects of transplanting neutrophin-3 (NT-3)-expressing bone marrow-derived mesenchymal stem cells (BMSCs) in a rat model of spinal cord injury (SCI).

Methods

Forty-eight adult female Sprague–Dawley rats were randomly assigned to three groups: the control, BMSC, and NT-3-BMSC groups. BMSCs were infected with NT-3-DsRed or DsRed lentivirus and injected into the cerebrospinal fluid (CSF) via lumbar puncture (LP) 7 days after SCI in the NT-3-BMSC and BMSC groups, respectively. The hind-limb motor function of all rats was recorded using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale on days 1, 3, 7, 14, 21, 28, and 35 after transplantation. Haematoxylin-eosin (HE) staining, immunofluorescence labelling, and western blotting were performed at the final time point.

Results

Expressions of NT-3, brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF) proteins increased significantly in the NT-3-BMSC group, and hind-limb locomotor functions improved significantly in the NT-3-BMSC group compared with the other two groups. The cystic cavity area was smallest in the NT-3-BMSC group. In the NT-3-BMSC group, neurofilament 200 (NF200) and glial fibrillary acidic protein (GFAP) expression levels around the lesions were significantly increased and decreased, respectively.

Conclusions

Our findings demonstrate that transplantation of NT-3 gene-modified BMSCs via LP can strengthen the therapeutic benefits of BMSC transplantation. We observed that these modified cells increased locomotor function recovery, promoted nerve regeneration, and improved the injured spinal cord microenvironment, suggesting that it could be a promising treatment for SCI.
Literature
1.
go back to reference Bakshi A, Hunter C, Swanger S, Lepore A, Fischer I (2004) Minimally invasive delivery of stem cells for spinal cord injury: advantages of the lumbar puncture technique. J Neurosurg Spine 1:330–337PubMedCrossRef Bakshi A, Hunter C, Swanger S, Lepore A, Fischer I (2004) Minimally invasive delivery of stem cells for spinal cord injury: advantages of the lumbar puncture technique. J Neurosurg Spine 1:330–337PubMedCrossRef
2.
go back to reference Barouch R, Schwartz M (2002) Autoreactive T cells induce neurotrophin production by immune and neural cells in injured rat optic nerve: implications for protective autoimmunity. FASEB J 16:1304–1306PubMed Barouch R, Schwartz M (2002) Autoreactive T cells induce neurotrophin production by immune and neural cells in injured rat optic nerve: implications for protective autoimmunity. FASEB J 16:1304–1306PubMed
3.
go back to reference Basso DM, Beattie MS, Bresnahan JC (1995) A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 12:1–21PubMedCrossRef Basso DM, Beattie MS, Bresnahan JC (1995) A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 12:1–21PubMedCrossRef
4.
go back to reference Besser M, Wank R (1999) Cutting edge: clonally restricted production of the neurotrophins brain-derived neurotrophic factor and neurotrophin-3 mRNA by human immune cells and Th1/Th2-polarized expression of their receptors. J Immunol 162:6303–6306PubMed Besser M, Wank R (1999) Cutting edge: clonally restricted production of the neurotrophins brain-derived neurotrophic factor and neurotrophin-3 mRNA by human immune cells and Th1/Th2-polarized expression of their receptors. J Immunol 162:6303–6306PubMed
5.
go back to reference Chopp M, Li Y (2002) Treatment of neural injury with marrow stromal cells. Lancet Neurol 1:92–100PubMedCrossRef Chopp M, Li Y (2002) Treatment of neural injury with marrow stromal cells. Lancet Neurol 1:92–100PubMedCrossRef
6.
go back to reference Constantini S, Young W (1994) The effects of methylprednisolone and the ganglioside GM1 on acute spinal cord injury in rats. J Neurosurg 80:97–111PubMedCrossRef Constantini S, Young W (1994) The effects of methylprednisolone and the ganglioside GM1 on acute spinal cord injury in rats. J Neurosurg 80:97–111PubMedCrossRef
7.
go back to reference Crigler L, Robey RC, Asawachaicharn A, Gaupp D, Phinney DG (2006) Human mesenchymal stem cell subpopulations express a variety of neuro-regulatory molecules and promote neuronal cell survival and neuritogenesis. Exp Neurol 198:54–64PubMedCrossRef Crigler L, Robey RC, Asawachaicharn A, Gaupp D, Phinney DG (2006) Human mesenchymal stem cell subpopulations express a variety of neuro-regulatory molecules and promote neuronal cell survival and neuritogenesis. Exp Neurol 198:54–64PubMedCrossRef
8.
go back to reference Dougherty KD, Dreyfus CF, Black IB (2000) Brain-derived neurotrophic factor in astrocytes, oligodendrocytes, and microglia/macrophages after spinal cord injury. Neurobiol Dis 7:574–585PubMedCrossRef Dougherty KD, Dreyfus CF, Black IB (2000) Brain-derived neurotrophic factor in astrocytes, oligodendrocytes, and microglia/macrophages after spinal cord injury. Neurobiol Dis 7:574–585PubMedCrossRef
9.
go back to reference Douglas-Escobar M, Rossignol C, Steindler D, Zheng T, Weiss MD (2012) Neurotrophin-induced migration and neuronal differentiation of multipotent astrocytic stem cells in vitro. PLoS ONE 7:e51706PubMedCentralPubMedCrossRef Douglas-Escobar M, Rossignol C, Steindler D, Zheng T, Weiss MD (2012) Neurotrophin-induced migration and neuronal differentiation of multipotent astrocytic stem cells in vitro. PLoS ONE 7:e51706PubMedCentralPubMedCrossRef
10.
go back to reference Elkabes S, DiCicco-Bloom EM, Black IB (1996) Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function. J Neurosci 16:2508–2521PubMed Elkabes S, DiCicco-Bloom EM, Black IB (1996) Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function. J Neurosci 16:2508–2521PubMed
11.
go back to reference Fujiwara Y, Tanaka N, Ishida O, Fujimoto Y, Murakami T, Kajihara H, Yasunaga Y, Ochi M (2004) Intravenously injected neural progenitor cells of transgenic rats can migrate to the injured spinal cord and differentiate into neurons, astrocytes and oligodendrocytes. Neurosci Lett 366:287–291PubMedCrossRef Fujiwara Y, Tanaka N, Ishida O, Fujimoto Y, Murakami T, Kajihara H, Yasunaga Y, Ochi M (2004) Intravenously injected neural progenitor cells of transgenic rats can migrate to the injured spinal cord and differentiate into neurons, astrocytes and oligodendrocytes. Neurosci Lett 366:287–291PubMedCrossRef
12.
go back to reference Goldberg JL, Barres BA (2000) The relationship between neuronal survival and regeneration. Annu Rev Neurosci 23:579–612PubMedCrossRef Goldberg JL, Barres BA (2000) The relationship between neuronal survival and regeneration. Annu Rev Neurosci 23:579–612PubMedCrossRef
13.
go back to reference Guo JS, Zeng YS, Li HB, Huang WL, Liu RY, Li XB, Ding Y, Wu LZ, Cai DZ (2007) Cotransplant of neural stem cells and NT-3 gene modified Schwann cells promote the recovery of transected spinal cord injury. Spinal Cord 45:15–24PubMedCrossRef Guo JS, Zeng YS, Li HB, Huang WL, Liu RY, Li XB, Ding Y, Wu LZ, Cai DZ (2007) Cotransplant of neural stem cells and NT-3 gene modified Schwann cells promote the recovery of transected spinal cord injury. Spinal Cord 45:15–24PubMedCrossRef
14.
go back to reference Hawryluk GW, Mothe A, Wang J, Wang S, Tator C, Fehlings MG (2012) An in vivo characterization of trophic factor production following neural precursor cell or bone marrow stromal cell transplantation for spinal cord injury. Stem Cells Dev 21:2222–2238PubMedCentralPubMedCrossRef Hawryluk GW, Mothe A, Wang J, Wang S, Tator C, Fehlings MG (2012) An in vivo characterization of trophic factor production following neural precursor cell or bone marrow stromal cell transplantation for spinal cord injury. Stem Cells Dev 21:2222–2238PubMedCentralPubMedCrossRef
15.
go back to reference Hofstetter CP, Schwarz EJ, Hess D, Widenfalk J, El Manira A, Prockop DJ, Olson L (2002) Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci U S A 99:2199–2204PubMedCentralPubMedCrossRef Hofstetter CP, Schwarz EJ, Hess D, Widenfalk J, El Manira A, Prockop DJ, Olson L (2002) Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci U S A 99:2199–2204PubMedCentralPubMedCrossRef
16.
go back to reference Ji JF, He BP, Dheen ST, Tay SS (2004) Interactions of chemokines and chemokine receptors mediate the migration of mesenchymal stem cells to the impaired site in the brain after hypoglossal nerve injury. Stem Cells 22:415–427PubMedCrossRef Ji JF, He BP, Dheen ST, Tay SS (2004) Interactions of chemokines and chemokine receptors mediate the migration of mesenchymal stem cells to the impaired site in the brain after hypoglossal nerve injury. Stem Cells 22:415–427PubMedCrossRef
17.
go back to reference Johnson PJ, Parker SR, Sakiyama-Elbert SE (2009) Controlled release of neurotrophin-3 from fibrin-based tissue engineering scaffolds enhances neural fiber sprouting following subacute spinal cord injury. Biotechnol Bioeng 104:1207–1214PubMedCentralPubMedCrossRef Johnson PJ, Parker SR, Sakiyama-Elbert SE (2009) Controlled release of neurotrophin-3 from fibrin-based tissue engineering scaffolds enhances neural fiber sprouting following subacute spinal cord injury. Biotechnol Bioeng 104:1207–1214PubMedCentralPubMedCrossRef
18.
go back to reference Kamei N, Tanaka N, Oishi Y, Hamasaki T, Nakanishi K, Sakai N, Ochi M (2007) BDNF, NT-3, and NGF released from transplanted neural progenitor cells promote corticospinal axon growth in organotypic cocultures. Spine (Phila Pa 1976) 32:1272–1278CrossRef Kamei N, Tanaka N, Oishi Y, Hamasaki T, Nakanishi K, Sakai N, Ochi M (2007) BDNF, NT-3, and NGF released from transplanted neural progenitor cells promote corticospinal axon growth in organotypic cocultures. Spine (Phila Pa 1976) 32:1272–1278CrossRef
19.
go back to reference Kamei N, Tanaka N, Oishi Y, Ishikawa M, Hamasaki T, Nishida K, Nakanishi K, Sakai N, Ochi M (2007) Bone marrow stromal cells promoting corticospinal axon growth through the release of humoral factors in organotypic cocultures in neonatal rats. J Neurosurg Spine 6:412–419PubMedCrossRef Kamei N, Tanaka N, Oishi Y, Ishikawa M, Hamasaki T, Nishida K, Nakanishi K, Sakai N, Ochi M (2007) Bone marrow stromal cells promoting corticospinal axon growth through the release of humoral factors in organotypic cocultures in neonatal rats. J Neurosurg Spine 6:412–419PubMedCrossRef
20.
go back to reference Kan EM, Ling EA, Lu J (2010) Stem cell therapy for spinal cord injury. Curr Med Chem 17:4492–4510PubMedCrossRef Kan EM, Ling EA, Lu J (2010) Stem cell therapy for spinal cord injury. Curr Med Chem 17:4492–4510PubMedCrossRef
21.
go back to reference Kang ES, Ha KY, Kim YH (2012) Fate of transplanted bone marrow derived mesenchymal stem cells following spinal cord injury in rats by transplantation routes. J Korean Med Sci 27:586–593PubMedCentralPubMedCrossRef Kang ES, Ha KY, Kim YH (2012) Fate of transplanted bone marrow derived mesenchymal stem cells following spinal cord injury in rats by transplantation routes. J Korean Med Sci 27:586–593PubMedCentralPubMedCrossRef
22.
go back to reference Kubinova S, Sykova E (2012) Biomaterials combined with cell therapy for treatment of spinal cord injury. Regen Med 7:207–224PubMedCrossRef Kubinova S, Sykova E (2012) Biomaterials combined with cell therapy for treatment of spinal cord injury. Regen Med 7:207–224PubMedCrossRef
23.
go back to reference Laurenzi MA, Barbany G, Timmusk T, Lindgren JA, Persson H (1994) Expression of mRNA encoding neurotrophins and neurotrophin receptors in rat thymus, spleen tissue and immunocompetent cells. Regulation of neurotrophin-4 mRNA expression by mitogens and leukotriene B4. Eur J Biochem 223:733–741PubMedCrossRef Laurenzi MA, Barbany G, Timmusk T, Lindgren JA, Persson H (1994) Expression of mRNA encoding neurotrophins and neurotrophin receptors in rat thymus, spleen tissue and immunocompetent cells. Regulation of neurotrophin-4 mRNA expression by mitogens and leukotriene B4. Eur J Biochem 223:733–741PubMedCrossRef
24.
go back to reference Li Y, Zhang WM, Wang TH (2011) Optimal location and time for neural stem cell transplantation into transected rat spinal cord. Cell Mol Neurobiol 31:407–414PubMedCrossRef Li Y, Zhang WM, Wang TH (2011) Optimal location and time for neural stem cell transplantation into transected rat spinal cord. Cell Mol Neurobiol 31:407–414PubMedCrossRef
25.
go back to reference Lin WP, Chen XW, Zhang LQ, Wu CY, Huang ZD, Lin JH (2013) Effect of neuroglobin genetically modified bone marrow mesenchymal stem cells transplantation on spinal cord injury in rabbits. PLoS ONE 8:e63444PubMedCentralPubMedCrossRef Lin WP, Chen XW, Zhang LQ, Wu CY, Huang ZD, Lin JH (2013) Effect of neuroglobin genetically modified bone marrow mesenchymal stem cells transplantation on spinal cord injury in rabbits. PLoS ONE 8:e63444PubMedCentralPubMedCrossRef
26.
go back to reference Liu WG, Wang ZY, Huang ZS (2011) Bone marrow-derived mesenchymal stem cells expressing the bFGF transgene promote axon regeneration and functional recovery after spinal cord injury in rats. Neurol Res 33:686–693PubMedCrossRef Liu WG, Wang ZY, Huang ZS (2011) Bone marrow-derived mesenchymal stem cells expressing the bFGF transgene promote axon regeneration and functional recovery after spinal cord injury in rats. Neurol Res 33:686–693PubMedCrossRef
28.
go back to reference Massey JM, Amps J, Viapiano MS, Matthews RT, Wagoner MR, Whitaker CM, Alilain W, Yonkof AL, Khalyfa A, Cooper NG, Silver J, Onifer SM (2008) Increased chondroitin sulfate proteoglycan expression in denervated brainstem targets following spinal cord injury creates a barrier to axonal regeneration overcome by chondroitinase ABC and neurotrophin-3. Exp Neurol 209:426–445PubMedCentralPubMedCrossRef Massey JM, Amps J, Viapiano MS, Matthews RT, Wagoner MR, Whitaker CM, Alilain W, Yonkof AL, Khalyfa A, Cooper NG, Silver J, Onifer SM (2008) Increased chondroitin sulfate proteoglycan expression in denervated brainstem targets following spinal cord injury creates a barrier to axonal regeneration overcome by chondroitinase ABC and neurotrophin-3. Exp Neurol 209:426–445PubMedCentralPubMedCrossRef
29.
go back to reference Murray M (2004) Cellular transplants: steps toward restoration of function in spinal injured animals. Prog Brain Res 143:133–146PubMed Murray M (2004) Cellular transplants: steps toward restoration of function in spinal injured animals. Prog Brain Res 143:133–146PubMed
30.
go back to reference Neuhuber B, Timothy Himes B, Shumsky JS, Gallo G, Fischer I (2005) Axon growth and recovery of function supported by human bone marrow stromal cells in the injured spinal cord exhibit donor variations. Brain Res 1035:73–85PubMedCrossRef Neuhuber B, Timothy Himes B, Shumsky JS, Gallo G, Fischer I (2005) Axon growth and recovery of function supported by human bone marrow stromal cells in the injured spinal cord exhibit donor variations. Brain Res 1035:73–85PubMedCrossRef
31.
go back to reference Nishida K, Tanaka N, Nakanishi K, Kamei N, Hamasaki T, Yanada S, Mochizuki Y, Ochi M (2006) Magnetic targeting of bone marrow stromal cells into spinal cord: through cerebrospinal fluid. Neuroreport 17:1269–1272PubMedCrossRef Nishida K, Tanaka N, Nakanishi K, Kamei N, Hamasaki T, Yanada S, Mochizuki Y, Ochi M (2006) Magnetic targeting of bone marrow stromal cells into spinal cord: through cerebrospinal fluid. Neuroreport 17:1269–1272PubMedCrossRef
32.
go back to reference Ohta M, Suzuki Y, Noda T, Ejiri Y, Dezawa M, Kataoka K, Chou H, Ishikawa N, Matsumoto N, Iwashita Y, Mizuta E, Kuno S, Ide C (2004) Bone marrow stromal cells infused into the cerebrospinal fluid promote functional recovery of the injured rat spinal cord with reduced cavity formation. Exp Neurol 187:266–278PubMedCrossRef Ohta M, Suzuki Y, Noda T, Ejiri Y, Dezawa M, Kataoka K, Chou H, Ishikawa N, Matsumoto N, Iwashita Y, Mizuta E, Kuno S, Ide C (2004) Bone marrow stromal cells infused into the cerebrospinal fluid promote functional recovery of the injured rat spinal cord with reduced cavity formation. Exp Neurol 187:266–278PubMedCrossRef
33.
go back to reference Okano H, Ogawa Y, Nakamura M, Kaneko S, Iwanama A, Toyama Y (2003) Transplantation of neural stem cells into the spinal cord after injury. Semin Cell Dev Biol 14:191–198PubMedCrossRef Okano H, Ogawa Y, Nakamura M, Kaneko S, Iwanama A, Toyama Y (2003) Transplantation of neural stem cells into the spinal cord after injury. Semin Cell Dev Biol 14:191–198PubMedCrossRef
34.
go back to reference Parr AM, Kulbatski I, Wang XH, Keating A, Tator CH (2008) Fate of transplanted adult neural stem/progenitor cells and bone marrow-derived mesenchymal stromal cells in the injured adult rat spinal cord and impact on functional recovery. Surg Neurol 70:600–607, discussion 607PubMedCrossRef Parr AM, Kulbatski I, Wang XH, Keating A, Tator CH (2008) Fate of transplanted adult neural stem/progenitor cells and bone marrow-derived mesenchymal stromal cells in the injured adult rat spinal cord and impact on functional recovery. Surg Neurol 70:600–607, discussion 607PubMedCrossRef
35.
go back to reference Parr AM, Tator CH, Keating A (2007) Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury. Bone Marrow Transplant 40:609–619PubMedCrossRef Parr AM, Tator CH, Keating A (2007) Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury. Bone Marrow Transplant 40:609–619PubMedCrossRef
36.
go back to reference Patapoutian A, Reichardt LF (2001) Trk receptors: mediators of neurotrophin action. Curr Opin Neurobiol 11:272–280PubMedCrossRef Patapoutian A, Reichardt LF (2001) Trk receptors: mediators of neurotrophin action. Curr Opin Neurobiol 11:272–280PubMedCrossRef
37.
go back to reference Pyle AD, Lock LF, Donovan PJ (2006) Neurotrophins mediate human embryonic stem cell survival. Nat Biotechnol 24:344–350PubMedCrossRef Pyle AD, Lock LF, Donovan PJ (2006) Neurotrophins mediate human embryonic stem cell survival. Nat Biotechnol 24:344–350PubMedCrossRef
38.
go back to reference Rabchevsky AG, Streit WJ (1998) Role of microglia in post injury repair and regeneration of the CNS. Ment Retard Dev Disabil Res Rev 4:187–192CrossRef Rabchevsky AG, Streit WJ (1998) Role of microglia in post injury repair and regeneration of the CNS. Ment Retard Dev Disabil Res Rev 4:187–192CrossRef
39.
go back to reference Rosenstein JM, Krum JM (2004) New roles for VEGF in nervous tissue—beyond blood vessels. Exp Neurol 187:246–253PubMedCrossRef Rosenstein JM, Krum JM (2004) New roles for VEGF in nervous tissue—beyond blood vessels. Exp Neurol 187:246–253PubMedCrossRef
41.
go back to reference Sasaki H, Tanaka N, Nakanishi K, Nishida K, Hamasaki T, Yamada K, Ochi M (2011) Therapeutic effects with magnetic targeting of bone marrow stromal cells in a rat spinal cord injury model. Spine (Phila Pa 1976) 36:933–938CrossRef Sasaki H, Tanaka N, Nakanishi K, Nishida K, Hamasaki T, Yamada K, Ochi M (2011) Therapeutic effects with magnetic targeting of bone marrow stromal cells in a rat spinal cord injury model. Spine (Phila Pa 1976) 36:933–938CrossRef
42.
go back to reference Satake K, Lou J, Lenke LG (2004) Migration of mesenchymal stem cells through cerebrospinal fluid into injured spinal cord tissue. Spine (Phila Pa 1976) 29:1971–1979CrossRef Satake K, Lou J, Lenke LG (2004) Migration of mesenchymal stem cells through cerebrospinal fluid into injured spinal cord tissue. Spine (Phila Pa 1976) 29:1971–1979CrossRef
43.
go back to reference Schiller MD, Mobbs RJ (2012) The historical evolution of the management of spinal cord injury. J Clin Neurosci 19:1348–1353PubMedCrossRef Schiller MD, Mobbs RJ (2012) The historical evolution of the management of spinal cord injury. J Clin Neurosci 19:1348–1353PubMedCrossRef
44.
go back to reference Shang AJ, Hong SQ, Xu Q, Wang HY, Yang Y, Wang ZF, Xu BN, Jiang XD, Xu RX (2011) NT-3-secreting human umbilical cord mesenchymal stromal cell transplantation for the treatment of acute spinal cord injury in rats. Brain Res 1391:102–113PubMedCrossRef Shang AJ, Hong SQ, Xu Q, Wang HY, Yang Y, Wang ZF, Xu BN, Jiang XD, Xu RX (2011) NT-3-secreting human umbilical cord mesenchymal stromal cell transplantation for the treatment of acute spinal cord injury in rats. Brain Res 1391:102–113PubMedCrossRef
45.
go back to reference Shen J, Zhong XM, Duan XH, Cheng LN, Hong GB, Bi XB, Liu Y (2009) Magnetic resonance imaging of mesenchymal stem cells labeled with dual (MR and fluorescence) agents in rat spinal cord injury. Acad Radiol 16:1142–1154PubMedCrossRef Shen J, Zhong XM, Duan XH, Cheng LN, Hong GB, Bi XB, Liu Y (2009) Magnetic resonance imaging of mesenchymal stem cells labeled with dual (MR and fluorescence) agents in rat spinal cord injury. Acad Radiol 16:1142–1154PubMedCrossRef
46.
go back to reference Shen L, Zeng W, Wu YX, Hou CL, Chen W, Yang MC, Li L, Zhang YF, Zhu CH (2013) Neurotrophin-3 accelerates wound healing in diabetic mice by promoting a paracrine response in mesenchymal stem cells. Cell Transplant 22:1011–1021PubMedCrossRef Shen L, Zeng W, Wu YX, Hou CL, Chen W, Yang MC, Li L, Zhang YF, Zhu CH (2013) Neurotrophin-3 accelerates wound healing in diabetic mice by promoting a paracrine response in mesenchymal stem cells. Cell Transplant 22:1011–1021PubMedCrossRef
47.
go back to reference Shumsky JS, Tobias CA, Tumolo M, Long WD, Giszter SF, Murray M (2003) Delayed transplantation of fibroblasts genetically modified to secrete BDNF and NT-3 into a spinal cord injury site is associated with limited recovery of function. Exp Neurol 184:114–130PubMedCrossRef Shumsky JS, Tobias CA, Tumolo M, Long WD, Giszter SF, Murray M (2003) Delayed transplantation of fibroblasts genetically modified to secrete BDNF and NT-3 into a spinal cord injury site is associated with limited recovery of function. Exp Neurol 184:114–130PubMedCrossRef
48.
go back to reference Sieck GC, Mantilla CB (2009) Role of neurotrophins in recovery of phrenic motor function following spinal cord injury. Respir Physiol Neurobiol 169:218–225PubMedCentralPubMedCrossRef Sieck GC, Mantilla CB (2009) Role of neurotrophins in recovery of phrenic motor function following spinal cord injury. Respir Physiol Neurobiol 169:218–225PubMedCentralPubMedCrossRef
49.
go back to reference Son BR, Marquez-Curtis LA, Kucia M, Wysoczynski M, Turner AR, Ratajczak J, Ratajczak MZ, Janowska-Wieczorek A (2006) Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met axes and involves matrix metalloproteinases. Stem Cells 24:1254–1264PubMedCrossRef Son BR, Marquez-Curtis LA, Kucia M, Wysoczynski M, Turner AR, Ratajczak J, Ratajczak MZ, Janowska-Wieczorek A (2006) Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met axes and involves matrix metalloproteinases. Stem Cells 24:1254–1264PubMedCrossRef
50.
go back to reference Song XY, Li F, Zhang FH, Zhong JH, Zhou XF (2008) Peripherally-derived BDNF promotes regeneration of ascending sensory neurons after spinal cord injury. PLoS ONE 3:e1707PubMedCentralPubMedCrossRef Song XY, Li F, Zhang FH, Zhong JH, Zhou XF (2008) Peripherally-derived BDNF promotes regeneration of ascending sensory neurons after spinal cord injury. PLoS ONE 3:e1707PubMedCentralPubMedCrossRef
51.
go back to reference Sykova E, Jendelova P (2005) Magnetic resonance tracking of implanted adult and embryonic stem cells in injured brain and spinal cord. Ann N Y Acad Sci 1049:146–160PubMedCrossRef Sykova E, Jendelova P (2005) Magnetic resonance tracking of implanted adult and embryonic stem cells in injured brain and spinal cord. Ann N Y Acad Sci 1049:146–160PubMedCrossRef
52.
go back to reference Tetzlaff W, Okon EB, Karimi-Abdolrezaee S, Hill CE, Sparling JS, Plemel JR, Plunet WT, Tsai EC, Baptiste D, Smithson LJ, Kawaja MD, Fehlings MG, Kwon BK (2011) A systematic review of cellular transplantation therapies for spinal cord injury. J Neurotrauma 28:1611–1682PubMedCentralPubMedCrossRef Tetzlaff W, Okon EB, Karimi-Abdolrezaee S, Hill CE, Sparling JS, Plemel JR, Plunet WT, Tsai EC, Baptiste D, Smithson LJ, Kawaja MD, Fehlings MG, Kwon BK (2011) A systematic review of cellular transplantation therapies for spinal cord injury. J Neurotrauma 28:1611–1682PubMedCentralPubMedCrossRef
53.
go back to reference Thuret S, Moon LD, Gage FH (2006) Therapeutic interventions after spinal cord injury. Nat Rev Neurosci 7:628–643PubMedCrossRef Thuret S, Moon LD, Gage FH (2006) Therapeutic interventions after spinal cord injury. Nat Rev Neurosci 7:628–643PubMedCrossRef
54.
go back to reference Ullal GR, Michalski B, Xu B, Racine RJ, Fahnestock M (2007) NT-3 modulates BDNF and proBDNF levels in naive and kindled rat hippocampus. Neurochem Int 50:866–871PubMedCrossRef Ullal GR, Michalski B, Xu B, Racine RJ, Fahnestock M (2007) NT-3 modulates BDNF and proBDNF levels in naive and kindled rat hippocampus. Neurochem Int 50:866–871PubMedCrossRef
55.
go back to reference Vanecek V, Zablotskii V, Forostyak S, Růžička J, Herynek V, Babič M, Jendelová P, Kubinová S, Dejneka A, Syková E (2012) Highly efficient magnetic targeting of mesenchymal stem cells in spinal cord injury. Int J Nanomedicine 7:3719–3730PubMedCentralPubMedCrossRef Vanecek V, Zablotskii V, Forostyak S, Růžička J, Herynek V, Babič M, Jendelová P, Kubinová S, Dejneka A, Syková E (2012) Highly efficient magnetic targeting of mesenchymal stem cells in spinal cord injury. Int J Nanomedicine 7:3719–3730PubMedCentralPubMedCrossRef
56.
go back to reference White RE, Jakeman LB (2008) Don’t fence me in: harnessing the beneficial roles of astrocytes for spinal cord repair. Restor Neurol Neurosci 26:197–214PubMedCentralPubMed White RE, Jakeman LB (2008) Don’t fence me in: harnessing the beneficial roles of astrocytes for spinal cord repair. Restor Neurol Neurosci 26:197–214PubMedCentralPubMed
57.
go back to reference Widenfalk J, Lipson A, Jubran M, Hofstetter C, Ebendal T, Cao Y, Olson L (2003) Vascular endothelial growth factor improves functional outcome and decreases secondary degeneration in experimental spinal cord contusion injury. Neuroscience 120:951–960PubMedCrossRef Widenfalk J, Lipson A, Jubran M, Hofstetter C, Ebendal T, Cao Y, Olson L (2003) Vascular endothelial growth factor improves functional outcome and decreases secondary degeneration in experimental spinal cord contusion injury. Neuroscience 120:951–960PubMedCrossRef
58.
go back to reference Wright KT, El Masri W, Osman A, Chowdhury J, Johnson WE (2011) Concise review: bone marrow for the treatment of spinal cord injury: mechanisms and clinical applications. Stem Cells 29:169–178PubMedCentralPubMedCrossRef Wright KT, El Masri W, Osman A, Chowdhury J, Johnson WE (2011) Concise review: bone marrow for the treatment of spinal cord injury: mechanisms and clinical applications. Stem Cells 29:169–178PubMedCentralPubMedCrossRef
59.
go back to reference Wu S, Suzuki Y, Ejiri Y, Noda T, Bai H, Kitada M, Kataoka K, Ohta M, Chou H, Ide C (2003) Bone marrow stromal cells enhance differentiation of cocultured neurosphere cells and promote regeneration of injured spinal cord. J Neurosci Res 72:343–351PubMedCrossRef Wu S, Suzuki Y, Ejiri Y, Noda T, Bai H, Kitada M, Kataoka K, Ohta M, Chou H, Ide C (2003) Bone marrow stromal cells enhance differentiation of cocultured neurosphere cells and promote regeneration of injured spinal cord. J Neurosci Res 72:343–351PubMedCrossRef
60.
go back to reference Yaghoobi MM, Mowla SJ (2006) Differential gene expression pattern of neurotrophins and their receptors during neuronal differentiation of rat bone marrow stromal cells. Neurosci Lett 397:149–154PubMedCrossRef Yaghoobi MM, Mowla SJ (2006) Differential gene expression pattern of neurotrophins and their receptors during neuronal differentiation of rat bone marrow stromal cells. Neurosci Lett 397:149–154PubMedCrossRef
61.
go back to reference Zhang W, Yan Q, Zeng YS, Zhang XB, Xiong Y, Wang JM, Chen SJ, Li Y, Bruce IC, Wu W (2010) Implantation of adult bone marrow-derived mesenchymal stem cells transfected with the neurotrophin-3 gene and pretreated with retinoic acid in completely transected spinal cord. Brain Res 1359:256–271PubMedCrossRef Zhang W, Yan Q, Zeng YS, Zhang XB, Xiong Y, Wang JM, Chen SJ, Li Y, Bruce IC, Wu W (2010) Implantation of adult bone marrow-derived mesenchymal stem cells transfected with the neurotrophin-3 gene and pretreated with retinoic acid in completely transected spinal cord. Brain Res 1359:256–271PubMedCrossRef
62.
go back to reference Zhao T, Yan W, Xu K, Qi Y, Dai X, Shi Z (2013) Combined treatment with platelet-rich plasma and brain-derived neurotrophic factor-overexpressing bone marrow stromal cells supports axonal remyelination in a rat spinal cord hemi-section model. Cytotherapy 15:792–804PubMedCrossRef Zhao T, Yan W, Xu K, Qi Y, Dai X, Shi Z (2013) Combined treatment with platelet-rich plasma and brain-derived neurotrophic factor-overexpressing bone marrow stromal cells supports axonal remyelination in a rat spinal cord hemi-section model. Cytotherapy 15:792–804PubMedCrossRef
Metadata
Title
Transplantation of neurotrophin-3-expressing bone mesenchymal stem cells improves recovery in a rat model of spinal cord injury
Authors
Ling-Jie Wang
Rui-Ping Zhang
Jian-Ding Li
Publication date
01-07-2014
Publisher
Springer Vienna
Published in
Acta Neurochirurgica / Issue 7/2014
Print ISSN: 0001-6268
Electronic ISSN: 0942-0940
DOI
https://doi.org/10.1007/s00701-014-2089-6

Other articles of this Issue 7/2014

Acta Neurochirurgica 7/2014 Go to the issue

How I Do It—Vascular

Occipital pial synangiosis