Skip to main content

Advertisement

SpringerLink
Log in

The effects of canine bone marrow stromal cells on neuritogenesis from dorsal root ganglion neurons in vitro

  • Original Article
  • Published:
Veterinary Research Communications Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

The present in vitro study was designed to evaluate whether canine bone marrow stromal cells (BMSCs) promote neurite outgrowth from dorsal root ganglion (DRG) neurons. Bone marrow aspirates were collected from iliac crests of three young adult dogs. DRG neurons were cultured on BMSCs, fibroblasts, or laminin substrates. DRG neurons were also cultured in BMSC- or fibroblast-conditioned media. DRG neurons grown on BMSCs extended longer neurites and developed a much more elaborate conformation of branching neurites compared to those on fibroblasts or laminin. Quantitative analysis revealed that these effects were associated with the emergence of increased numbers of primary and branching neurites. The effect appears to be dependent upon cell-cell interactions rather than by elaboration of diffusible molecules. With more extensive investigations into the basic biology of canine BMSCs, their ability for promoting neurite outgrowth may be translated into a novel therapeutic strategy for dogs with a variety of neurological disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Akiyama Y, Radtke C, Kocsis JD (2002) Remyelination of the rat spinal cord by transplantation of identified bone marrow stromal cells. J Neurosci 22:6623–6630.

    PubMed  CAS  Google Scholar 

  • Arinzeh TL, Peter SJ, Archambault MP, van den Bos C, Gordon S, Kraus K, Smith A, Kadiyala S (2003) Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. J Bone Joint Surg Am 85-A:1927–1935.

    PubMed  Google Scholar 

  • Arnhold S, Klein H, Klinz FJ, Absenger Y, Schmidt A, Schinkothe T, Brixius K, Kozlowski J, Desai B, Bloch W, Addicks K (2006) Human bone marrow stroma cells display certain neural characteristics and integrate in the subventricular compartment after injection into the liquor system. Eur J Cell Biol 85:551–565. doi:10.1016/j.ejcb.2006.01.015.

    Article  PubMed  CAS  Google Scholar 

  • Auffray I, Chevalier S, Froger J, Izac B, Vainchenker W, Gascan H, Coulombel L (1996) Nerve growth factor is involved in the supportive effect by bone marrow-derived stromal cells of the factor-dependent human cell line UT-7. Blood 88:1608–1618.

    PubMed  CAS  Google Scholar 

  • Azizi SA, Stokes D, Augelli BJ, DiGirolamo C, Prockop DJ (1998) Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats-similarities to astrocyte grafts. Proc Natl Acad Sci U S A 95:3908–3913. doi:10.1073/pnas.95.7.3908.

    Article  PubMed  CAS  Google Scholar 

  • Bartunek J, Croissant JD, Wijns W, Gofflot S, de Lavareille A, Vanderheyden M, Kaluzhny Y, Mazouz N, Willemsen P, Penicka M, Mathieu M, Homsy C, De Bruyne B, McEntee K, Lee IW, Heyndrickx GR (2007) Pretreatment of adult bone marrow mesenchymal stem cells with cardiomyogenic growth factors and repair of the chronically infarcted myocardium. Am J Physiol Heart Circ Physiol 292:H1095–1104. doi:10.1152/ajpheart.01009.2005.

    Article  PubMed  CAS  Google Scholar 

  • Bruder SP, Kraus KH, Goldberg VM, Kadiyala S (1998) The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects. J Bone Joint Surg Am 80:985–996.

    PubMed  CAS  Google Scholar 

  • Chakrabortty S, Kitada M, Matsumoto N, Taketomi M, Kimura K, Ide C (2000) Choroid plexus ependymal cells enhance neurite outgrowth from dorsal root ganglion neurons in vitro. J Neurocytol 29:707–717. doi:10.1023/A:1010930819854.

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M, Chopp M (2001) Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 32:1005–1011.

    PubMed  CAS  Google Scholar 

  • Chen X, Li Y, Wang L, Katakowski M, Zhang L, Chen J, Xu Y, Gautam SC, Chopp M (2002a) Ischemic rat brain extracts induce human marrow stromal cell growth factor production. Neuropathology 22:275–279. doi:10.1046/j.1440-1789.2002.00450.x.

    Article  PubMed  Google Scholar 

  • Chen X, Katakowski M, Li Y, Lu D, Wang L, Zhang L, Chen J, Xu Y, Gautam S, Mahmood A, Chopp M (2002b) Human bone marrow stromal cell cultures conditioned by traumatic brain tissue extracts: growth factor production. J Neurosci Res 69:687–691. doi:10.1002/jnr.10334.

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Zhang ZG, Li Y, Wang L, Xu YX, Gautam SC, Lu M, Zhu Z, Chopp M (2003) Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats. Circ Res 92:692–699. doi:10.1161/01.RES.0000063425.51108.8D.

    Article  PubMed  CAS  Google Scholar 

  • Chen Q, Long Y, Yuan X, Zou L, Sun J, Chen S, Perez-Polo JR, Yang K (2005) Protective effects of bone marrow stromal cell transplantation in injured rodent brain: synthesis of neurotrophic factors. J Neurosci Res 80:611–619. doi:10.1002/jnr.20494.

    Article  PubMed  CAS  Google Scholar 

  • Chopp M, Zhang XH, Li Y, Wang L, Chen J, Lu D, Lu M, Rosenblum M (2000) Spinal cord injury in rat: treatment with bone marrow stromal cell transplantation. Neuroreport 11:3001–3005. doi:10.1097/00001756-200009110-00035.

    Article  PubMed  CAS  Google Scholar 

  • Cogle CR, Yachnis AT, Laywell ED, Zander DS, Wingard JR, Steindler DA, Scott EW (2004) Bone marrow transdifferentiation in brain after transplantation: a retrospective study. Lancet 363:1432–1437. doi:10.1016/S0140-6736(04)16102-3.

    Article  PubMed  CAS  Google Scholar 

  • 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 198:54–64. doi:10.1016/j.expneurol.2005.10.029.

    Article  PubMed  CAS  Google Scholar 

  • David S, Aguayo AJ (1981) Axonal elongation into peripheral nervous system “bridges” after central nervous system injury in adult rats. Science 214:931–933. doi:10.1126/science.6171034.

    Article  PubMed  CAS  Google Scholar 

  • DeKosky ST, Goss JR, Miller PD, Styren SD, Kochanek PM, Marion D (1994) Upregulation of nerve growth factor following cortical trauma. Exp Neurol 130:173–177. doi:10.1006/exnr.1994.1196.

    Article  PubMed  CAS  Google Scholar 

  • Deng W, Obrocka M, Fischer I, Prockop DJ (2001) In vitro differentiation of human marrow stromal cells into early progenitors of neural cells by conditions that increase intracellular cyclic AMP. Biochem Biophys Res Commun 282:148–152. doi:10.1006/bbrc.2001.4570.

    Article  PubMed  CAS  Google Scholar 

  • Deng J, Petersen BE, Steindler DA, Jorgensen ML, Laywell ED (2006) Mesenchymal stem cells spontaneously express neural proteins in culture and are neurogenic after transplantation. Stem Cells 24:1054–1064. doi:10.1634/stemcells.2005-0370.

    Article  PubMed  CAS  Google Scholar 

  • Dormady SP, Bashayan O, Dougherty R, Zhang XM, Basch RS (2001) Immortalized multipotential mesenchymal cells and the hematopoietic microenvironment. J Hematother Stem Cell Res 10:125–140. doi:10.1089/152581601750098372.

    Article  PubMed  CAS  Google Scholar 

  • d’Ortho MP, Will H, Atkinson S, Butler G, Messent A, Gavrilovic J, Smith B, Timpl R, Zardi L, Murphy G (1997) Membrane-type matrix metalloproteinases 1 and 2 exhibit broad-spectrum proteolytic capacities comparable to many matrix metalloproteinases. Eur J Biochem 250:751–757.

    Article  PubMed  Google Scholar 

  • Fallon JR (1985a) Neurite guidance by non-neuronal cells in culture: preferential outgrowth of peripheral neurites on glial as compared to nonglial cell surfaces. J Neurosci 5:3169–3177.

    PubMed  CAS  Google Scholar 

  • Fallon JR (1985b) Preferential outgrowth of central nervous system neurites on astrocytes and Schwann cells as compared with nonglial cells in vitro. J Cell Biol 100:198–207.

    Article  PubMed  CAS  Google Scholar 

  • Fosang AJ, Neame PJ, Last K, Hardingham TE, Murphy G, Hamilton JA (1992) The interglobular domain of cartilage aggrecan is cleaved by PUMP, gelatinases, and cathepsin B. J Biol Chem 267:19470–19474.

    PubMed  CAS  Google Scholar 

  • Garcia R, Aguiar J, Alberti E, de la Cuetara K, Pavon N (2004) Bone marrow stromal cells produce nerve growth factor and glial cell line-derived neurotrophic factors. Biochem Biophys Res Commun 316:753–754.

    Article  PubMed  CAS  Google Scholar 

  • Goss JR, O’Malley ME, Zou L, Styren SD, Kochanek PM, DeKosky ST (1998) Astrocytes are the major source of nerve growth factor upregulation following traumatic brain injury in the rat. Exp Neurol 149:301–309.

    Article  PubMed  CAS  Google Scholar 

  • Grayson WL, Ma T, Bunnell B (2004) Human mesenchymal stem cells tissue development in 3D PET matrices. Biotechnol Prog 20:905–912.

    Article  PubMed  CAS  Google Scholar 

  • Hammond EN, Tetzlaff W, Mestres P, Giehl KM (1999) BDNF, but not NT-3, promotes long-term survival of axotomized adult rat corticospinal neurons in vivo. Neuroreport 10:2671–2675.

    Article  PubMed  CAS  Google Scholar 

  • Hasegawa N, Kawaguchi H, Hirachi A, Takeda K, Mizuno N, Nishimura M, Koike C, Tsuji K, Iba H, Kato Y, Kurihara H (2006) Behavior of Transplanted Bone Marrow-Derived Mesenchymal Stem Cells in Periodontal Defects. J Periodontol 77:1003–1007.

    Article  PubMed  Google Scholar 

  • 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 99:2199–2204.

    Article  PubMed  CAS  Google Scholar 

  • Kadiyala S, Young RG, Thiede MA, Bruder SP (1997) Culture expanded canine mesenchymal stem cells possess osteochondrogenic potential in vivo and in vitro. Cell Transplant 6:125–134.

    Article  PubMed  CAS  Google Scholar 

  • Kamishina H, Deng J, Oji T, Cheeseman JA, Clemmons RM (2006) Expression of neural markers on bone marrow-derived canine mesenchymal stem cells. Am J Vet Res 67:1921–1928.

    Article  PubMed  CAS  Google Scholar 

  • Kimura K, Matsumoto N, Kitada M, Mizoguchi A, Ide C (2004) Neurite outgrowth from hippocampal neurons is promoted by choroid plexus ependymal cells in vitro. J Neurocytol 33:465–476.

    PubMed  CAS  Google Scholar 

  • Kohno K, Kawakami T, Hiruma H (2005) Effects of soluble laminin on organelle transport and neurite growth in cultured mouse dorsal root ganglion neurons: difference between primary neurites and branches. J Cell Physiol 205:253–261.

    Article  PubMed  CAS  Google Scholar 

  • Kopen GC, Prockop DJ, Phinney DG (1999) Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci U S A 96:10711–10716.

    Article  PubMed  CAS  Google Scholar 

  • Lee J, Kuroda S, Shichinohe H, Ikeda J, Seki T, Hida K, Tada M, Sawada K, Iwasaki Y (2003) Migration and differentiation of nuclear fluorescence-labeled bone marrow stromal cells after transplantation into cerebral infarct and spinal cord injury in mice. Neuropathology 23:169–180.

    Article  PubMed  Google Scholar 

  • Li Y, Chen J, Chen XG, Wang L, Gautam SC, Xu YX, Katakowski M, Zhang LJ, Lu M, Janakiraman N, Chopp M (2002) Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery. Neurology 59:514–523.

    PubMed  CAS  Google Scholar 

  • Lu P, Blesch A, Tuszynski MH (2001) Neurotrophism without neurotropism: BDNF promotes survival but not growth of lesioned corticospinal neurons. J Comp Neurol 436:456–470.

    Article  PubMed  CAS  Google Scholar 

  • Mahmood A, Lu D, Qu C, Goussev A, Chopp M (2005) Human marrow stromal cell treatment provides long-lasting benefit after traumatic brain injury in rats. Neurosurgery 57:1026–1031, discussion 1026–1031.

    Article  PubMed  Google Scholar 

  • Mezey E, Key S, Vogelsang G, Szalayova I, Lange GD, Crain B (2003) Transplanted bone marrow generates new neurons in human brains. Proc Natl Acad Sci U S A 100:1364–1369.

    Article  PubMed  CAS  Google Scholar 

  • Mocchetti I, Wrathall JR (1995) Neurotrophic factors in central nervous system trauma. J Neurotrauma 12:853–870.

    Article  PubMed  CAS  Google Scholar 

  • 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 1035:73–85.

    Article  PubMed  CAS  Google Scholar 

  • Oblander SA, Ensslen-Craig SE, Longo FM, Brady-Kalnay SM (2007) E-cadherin promotes retinal ganglion cell neurite outgrowth in a protein tyrosine phosphatase-mu-dependent manner. Mol Cell Neurosci 34:481–492.

    Article  PubMed  CAS  Google Scholar 

  • 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 187:266–278.

    Article  PubMed  CAS  Google Scholar 

  • Orr DJ, Smith RA (1988) Neuronal maintenance and neurite extension of adult mouse neurones in non-neuronal cell-reduced cultures is dependent on substratum coating. J Cell Sci 91 Pt 4:555–561.

    PubMed  Google Scholar 

  • Park HC, Shim YS, Ha Y, Yoon SH, Park SR, Choi BH, Park HS (2005) Treatment of complete spinal cord injury patients by autologous bone marrow cell transplantation and administration of granulocyte-macrophage colony stimulating factor. Tissue Eng 11:913–922.

    Article  PubMed  CAS  Google Scholar 

  • Passi A, Negrini D, Albertini R, Miserocchi G, De Luca G (1999) The sensitivity of versican from rabbit lung to gelatinase A (MMP-2) and B (MMP-9) and its involvement in the development of hydraulic lung edema. FEBS Lett 456:93–96.

    Article  PubMed  CAS  Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147.

    Article  PubMed  CAS  Google Scholar 

  • Price RD, Oe T, Yamaji T, Matsuoka N (2006) A simple, flexible, nonfluorescent system for the automated screening of neurite outgrowth. J Biomol Screen 11:155–164.

    Article  PubMed  CAS  Google Scholar 

  • Puch S, Armeanu S, Kibler C, Johnson KR, Muller CA, Wheelock MJ, Klein G (2001) N-cadherin is developmentally regulated and functionally involved in early hematopoietic cell differentiation. J Cell Sci 114:1567–1577.

    PubMed  CAS  Google Scholar 

  • Richardson PM, McGuinness UM, Aguayo AJ (1980) Axons from CNS neurons regenerate into PNS grafts. Nature 284:264–265.

    Article  PubMed  CAS  Google Scholar 

  • Sanchez-Ramos J, Song S, Cardozo-Pelaez F, Hazzi C, Stedeford T, Willing A, Freeman TB, Saporta S, Janssen W, Patel N, Cooper DR, Sanberg PR (2000) Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 164:247–256.

    Article  PubMed  CAS  Google Scholar 

  • Schense JC, Bloch J, Aebischer P, Hubbell JA (2000) Enzymatic incorporation of bioactive peptides into fibrin matrices enhances neurite extension. Nat Biotechnol 18:415–419.

    Article  PubMed  CAS  Google Scholar 

  • Smith PM, Jeffery ND (2006) Histological and ultrastructural analysis of white matter damage after naturally-occurring spinal cord injury. Brain Pathol 16:99–109.

    Article  PubMed  Google Scholar 

  • Smith RA, Orr DJ (1987) The survival of adult mouse sensory neurons in vitro is enhanced by natural and synthetic substrata, particularly fibronectin. J Neurosci Res 17:265–270.

    Article  PubMed  CAS  Google Scholar 

  • 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 24:1254–1264.

    Article  PubMed  CAS  Google Scholar 

  • Song S, Kamath S, Mosquera D, Zigova T, Sanberg P, Vesely DL, Sanchez-Ramos J (2004) Expression of brain natriuretic peptide by human bone marrow stromal cells. Exp Neurol 185:191–197.

    Article  PubMed  CAS  Google Scholar 

  • Volk SW, Diefenderfer DL, Christopher SA, Haskins ME, Leboy PS (2005) Effects of osteogenic inducers on cultures of canine mesenchymal stem cells. Am J Vet Res 66:1729–1737.

    Article  PubMed  Google Scholar 

  • Wang Y, Galvan V, Gorostiza O, Ataie M, Jin K, Greenberg DA (2006) Vascular endothelial growth factor improves recovery of sensorimotor and cognitive deficits after focal cerebral ischemia in the rat. Brain Res 1115:186–193.

    Article  PubMed  CAS  Google Scholar 

  • Woodbury D, Schwarz EJ, Prockop DJ, Black IB (2000) Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 61:364–370.

    Article  PubMed  CAS  Google Scholar 

  • Wright KT, El Masri W, Osman A, Roberts S, Chamberlain G, Ashton BA, Johnson WE (2007) Bone marrow stromal cells stimulate neurite outgrowth over neural proteoglycans (CSPG), myelin associated glycoprotein and Nogo-A. Biochem Biophys Res Commun 354:559–566.

    Article  PubMed  CAS  Google Scholar 

  • Wu QY, Li J, Feng ZT, Wang TH (2007) Bone marrow stromal cells of transgenic mice can improve the cognitive ability of an Alzheimer’s disease rat model. Neurosci Lett 417:281–285.

    Article  PubMed  CAS  Google Scholar 

  • Yoon SH, Shim YS, Park YH, Chung JK, Nam JH, Kim MO, Park HC, Park SR, Min BH, Kim EY, Choi BH, Park H, Ha Y (2007) Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: Phase I/II clinical trial. Stem Cells 25:2066–2073.

    Article  PubMed  Google Scholar 

  • Zhang ZG, Zhang L, Jiang Q, Zhang R, Davies K, Powers C, Bruggen N, Chopp M (2000) VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J Clin Invest 106:829–838.

    Article  PubMed  CAS  Google Scholar 

  • Zhao LR, Duan WM, Reyes M, Keene CD, Verfaillie CM, Low WC (2002) Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol 174:11–20.

    Article  PubMed  Google Scholar 

Download references

Acknowledgement

We thank Harumi Kamishina for her contribution on morphometric neurite analyses.

Author information

Authors and Affiliations

  1. Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, 32610-0126, USA

    Hiroaki Kamishina, Jennifer A. Cheeseman & Roger M. Clemmons

  2. Department of Veterinary Clinical Medicine, Faculty of Agriculture, Iwate University, 3-18-8 Ueda, Morioka, Iwate, Japan

    Hiroaki Kamishina

Authors
  1. Hiroaki Kamishina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jennifer A. Cheeseman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roger M. Clemmons
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroaki Kamishina.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kamishina, H., Cheeseman, J.A. & Clemmons, R.M. The effects of canine bone marrow stromal cells on neuritogenesis from dorsal root ganglion neurons in vitro. Vet Res Commun 33, 645–657 (2009). https://doi.org/10.1007/s11259-009-9213-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11259-009-9213-8

Keywords

Search

Navigation