Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2012

Open Access 01-12-2012 | Research article

Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system

Authors: Victor Tulio Ribeiro-Resende, Alvaro Carrier-Ruiz, Robertha M R Lemes, Ricardo A M Reis, Rosalia Mendez-Otero

Published in: Molecular Neurodegeneration | Issue 1/2012

Login to get access

Abstract

Background

Among the essential biological roles of bone marrow-derived cells, secretion of many soluble factors is included and these small molecules can act upon specific receptors present in many tissues including the nervous system. Some of the released molecules can induce proliferation of Schwann cells (SC), satellite cells and lumbar spinal cord astrocytes during early steps of regeneration in a rat model of sciatic nerve transection. These are the major glial cell types that support neuronal survival and axonal growth following peripheral nerve injury. Fibroblast growth factor-2 (FGF-2) is the main mitogenic factor for SCs and is released in large amounts by bone marrow-derived cells, as well as by growing axons and endoneurial fibroblasts during development and regeneration of the peripheral nervous system (PNS).

Results

Here we show that bone marrow-derived cell treatment induce an increase in the expression of FGF-2 in the sciatic nerve, dorsal root ganglia and the dorsolateral (DL) region of the lumbar spinal cord (LSC) in a model of sciatic nerve transection and connection into a hollow tube. SCs in culture in the presence of bone marrow derived conditioned media (CM) resulted in increased proliferation and migration. This effect was reduced when FGF-2 was neutralized by pretreating BMMC or CM with a specific antibody. The increased expression of FGF-2 was validated by RT-PCR and immunocytochemistry in co-cultures of bone marrow derived cells with sciatic nerve explants and regenerating nerve tissue respectivelly.

Conclusion

We conclude that FGF-2 secreted by BMMC strongly increases early glial proliferation, which can potentially improve PNS regeneration.
Appendix
Available only for authorised users
Literature
1.
Chen ZL, Yu WM, Strickland S: Peripheral Regeneration. Annu Rev Neurosci. 2007, 30: 209-233. 10.1146/annurev.neuro.30.051606.094337.CrossRefPubMed
2.
Jessen KR, Mirsky R: Schwann cells and their precursors emerge as major regulators of nerve development. Trends Neurosci. 1999, 22: 402-410. 10.1016/S0166-2236(98)01391-5.CrossRefPubMed
3.
Goldberg JL, Barres BA: The relationship between neuronal survival and regeneration. Annu Rev Neurosci. 2000, 23: 579-612. 10.1146/annurev.neuro.23.1.579.CrossRefPubMed
4.
Vargas ME, Barres BA: Why is Wallerian degeneration in the CNS so slow?. Annu Rev Neurosci. 2007, 30: 153-179. 10.1146/annurev.neuro.30.051606.094354.CrossRefPubMed
5.
Ribeiro-Resende VT, Pimentel-Coelho PM, Mesentier-Louro LA, Mendez RM, Mello-Silva JP, Cabral-da-Silva MC, de Mello FG, de Melo Reis RA, Mendez-Otero R: Trophic activity derived from bone marrow mononuclear cells increases peripheral nerve regeneration by acting on both neuronal and glial cell populations. Neuroscience. 2009, 159: 540-549. 10.1016/j.neuroscience.2008.12.059.CrossRefPubMed
6.
Martinelli C, Sartori P, De Palo S, Ledda M, Pannese E: Increase in number of the gap junctions between satellite neuroglial cells during lifetime: an ultrastructural study in rabbit spinal ganglia from youth to extremely advanced age. Brain Res Bull. 2005, 67: 19-23. 10.1016/j.brainresbull.2005.05.021.CrossRefPubMed
7.
Huang TY, Cherkas PS, Rosenthal DW, Hanani M: Dye coupling among satellite glial cells in mammalian dorsal root ganglia. Brain Res. 2005, 1036: 42-49. 10.1016/j.brainres.2004.12.021.CrossRefPubMed
8.
Pannese E, Ledda M, Cherkas PS, Huang TY, Hanani M: Satellite cell reactions to axon injury of sensory ganglion neurons: increase in number of gap junctions and formation of bridges connecting previously separate perineuronal sheaths. Anat Embryol (Berl). 2003, 206: 337-347.
9.
Thippeswamy T, McKay JS, Morris R, Quinn J, Wong LF, Murphy D: Glial-mediated neuroprotection: evidence for the protective role of the NO-cGMP pathway via neuron-glial communication in the peripheral nervous system. GLIA. 2005, 49: 197-210. 10.1002/glia.20105.CrossRefPubMed
10.
Grothe C, Haastert K, Jungnickel J: Physiological function and putative therapeutic impact of the FGF-2 system in peripheral nerve regeneration–lessons from in vivo studies in mice and rats. Brain Res Rev. 2006, 51: 293-299. 10.1016/j.brainresrev.2005.12.001.CrossRefPubMed
11.
Jungnickel J, Claus P, Gransalke K, Timmer M, Grothe C: Targeted disruption of the FGF-2 gene affects the response to peripheral nerve injury. Mol Cell Neurosci. 2004, 25: 444-452. 10.1016/j.mcn.2003.11.007.CrossRefPubMed
12.
Jungnickel J, Klutzny A, Guhr S, Meyer K, Grothe C: Regulation of neuronal death and calcitonin gene-related peptide by fibroblast growth factor-2 and FGFR3 after peripheral nerve injury: evidence from mouse mutants. Neuroscience. 2005, 134: 1343-1350. 10.1016/j.neuroscience.2005.04.066.CrossRefPubMed
13.
Haastert K, Lipokatic E, Fischer M, Timmer M, Grothe C: Differentially promoted peripheral nerve regeneration by grafted Schwann cells over-expressing different FGF-2 isoforms. Neurobiol Dis. 2006, 21: 138-153. 10.1016/j.nbd.2005.06.020.CrossRefPubMed
14.
Timmer M, Muller-Ostermeyer F, Kloth V, Winkler C, Grothe C, Nikkhah G: Enhanced survival, reinnervation, and functional recovery of intrastriatal dopamine grafts co-transplanted with Schwann cells overexpressing high molecular weight FGF-2 isoforms. Exp Neurol. 2004, 187: 118-136. 10.1016/j.expneurol.2004.01.013.CrossRefPubMed
15.
Zaverucha-do-Valle C, Gubert F, Bargas-Rega M, Coronel JL, Mesentier-Louro LA, Mencalha A, Abdelhay E, Santiago MF, Mendez-Otero R: Bone marrow mononuclear cells increase retinal ganglion cell survival and axon regeneration in the adult rat. Cell Transplant. 2010, 20: 391-406.CrossRefPubMed
16.
Fidelis-de-Oliveira P, Werneck-de-Castro JPS, Pinho-Ribeiro V, Shalom BCM, Nascimento-Silva JA, Souza RH Costa E, Cruz IS, Rangel RR, Goldenberg RCS, Campos-de-Carvalho AC: Soluble factors from multipotent mesenchymal stromal cells have antinecrotic effect on cardiomyocytes in vitro and improve cardiac function in infarcted rat hearts. Cell Transplant. 2012, in press
17.
Reis RA, Da Silva MC C, Santos NE Loureiro D, Bampton E, Taylor JS, De Mello FG, Linden R: Sympathetic neuronal survival induced by retinal trophic factors. J Neurobiol. 2002, 50: 13-23. 10.1002/neu.10008.CrossRefPubMed
18.
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR: Multilineage potential of adult human mesenchymal stem cells. Science. 1999, 284: 143-147. 10.1126/science.284.5411.143.CrossRefPubMed
19.
Pereira Lopes FR, Frattini F, Marques SA, Almeida FM, de Moura Campos LC, Langone F, Lora S, Borojevic R, Martinez AM: Transplantation of bone-marrow-derived cells into a nerve guide resulted in transdiffe into Schwann cells and effective regeneration of transected mouse sciatic nerve. Micron. 2010, 41: 783-790. 10.1016/j.micron.2010.05.010.CrossRefPubMed
20.
Shyu WC, Liu DD, Lin SZ, Li WW, Su CY, Chang YC, Wang HJ, Wang HW, Tsai CH, Li H: Implantation of olfactory ensheathing cells promotes neuroplasticity in murine models of stroke. J Clin Invest. 2008, 118: 2482-2495. 10.1172/JCI34363.PubMedCentralCrossRefPubMed
21.
Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM: Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002, 418: 41-49. 10.1038/nature00870.CrossRefPubMed
22.
Wagers AJ, Sherwood RI, Christensen JL, Weissman IL: Little evidence for developmental plasticity of adult hematopoietic stem cells. Science. 2002, 297: 2256-2259. 10.1126/science.1074807.CrossRefPubMed
23.
Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, Nakano Y, Meyer EM, Morel L, Petersen BE, Scott EW: Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature. 2002, 416: 542-545. 10.1038/nature730.CrossRefPubMed
24.
Wurmser AE, Gage FH: Stem cells: cell fusion causes confusion. Nature. 2002, 416: 485-487. 10.1038/416485a.CrossRefPubMed
25.
Kerschensteiner M, Gallmeier E, Behrens L, Leal VV, Misgeld T, Klinkert WE, Kolbeck R, Hoppe E, Oropeza-Wekerle RL, Bartke I, Stadelmann C, Lassmann H, Wekerle H, Hohlfeld R: 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. 1999, 189: 865-870. 10.1084/jem.189.5.865.PubMedCentralCrossRefPubMed
26.
Sieminski AL, Hebbel RP, Gooch KJ: Improved microvascular network in vitro by human blood outgrowth endothelial cells relative to vessel-derived endothelial cells. Tissue Eng. 2005, 11: 1332-1345. 10.1089/ten.2005.11.1332.CrossRefPubMed
27.
Zassler B, Humpel C: Transplantation of NGF secreting primary monocytes counteracts NMDA-induced cell death of rat cholinergic neurons in vivo. Exp Neurol. 2006, 198: 391-400. 10.1016/j.expneurol.2005.12.009.CrossRefPubMed
28.
Tang J, Hua Y, Su J, Zhang P, Zhu X, Wu L, Niu Q, Xiao H, Ding X: Expression of VEGF and neural repair after alprostadil treatment in a rat model of sciatic nerve crush injury. Neurol India. 2009, 57: 387-394. 10.4103/0028-3886.55583.CrossRefPubMed
29.
Fawcett JW, Keynes RJ: Peripheral nerve regeneration. Annu Rev Neurosci. 1990, 13: 43-60. 10.1146/annurev.ne.13.030190.000355.CrossRefPubMed
30.
Schmidt CE, Leach JB: Neural tissue engineering: strategies for repair and regeneration. Annu Rev Biomed Eng. 2003, 5: 293-347. 10.1146/annurev.bioeng.5.011303.120731.CrossRefPubMed
31.
Ming GL, Song H: Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci. 2005, 28: 223-250. 10.1146/annurev.neuro.28.051804.101459.CrossRefPubMed
32.
Markus A, Patel TD, Snider WD: Neurotrophic factors and axonal growth. Curr Opin Neurobiol. 2002, 12: 523-531. 10.1016/S0959-4388(02)00372-0.CrossRefPubMed
33.
Chevet E, Lemaître G, Janjic N, Barritault D, Bikfalvi A, Katinka MD: Fibroblast growth factor receptors participate in the control of mitogen-activated protein kinase activity during nerve growth factor-induced neuronal differentiation of PC12 cells. J Biol Chem. 1999, 274: 20901-20908. 10.1074/jbc.274.30.20901.CrossRefPubMed
34.
Lewin GR, Barde YA: Physiology of the neurotrophins. Annu Rev Neurosci. 1996, 19: 289-317. 10.1146/annurev.ne.19.030196.001445.CrossRefPubMed
35.
Liu RY, Snider WD: Different signaling pathways mediate regenerative versus developmental sensory axon growth. J Neurosci. 2001, 21: RC164-PubMed
36.
Hara MR, Snyder SH: Cell signaling and neuronal death. Annu Rev Pharmacol Toxicol. 2007, 47: 117-141. 10.1146/annurev.pharmtox.47.120505.105311.CrossRefPubMed
37.
Barres BA: The mystery and magic of glia: a perspective on their roles in health and disease. Neuron. 2008, 60: 430-440. 10.1016/j.neuron.2008.10.013.CrossRefPubMed
Metadata
Title
Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system
Authors
Victor Tulio Ribeiro-Resende
Alvaro Carrier-Ruiz
Robertha M R Lemes
Ricardo A M Reis
Rosalia Mendez-Otero
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2012
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/1750-1326-7-34

Other articles of this Issue 1/2012

Molecular Neurodegeneration 1/2012 Go to the issue

Research article

Defective lysosomal proteolysis and axonal transport are early pathogenic events that worsen with age leading to increased APP metabolism and synaptic Abeta in transgenic APP/PS1 hippocampus

Research article

Combined exposure to Maneb and Paraquat alters transcriptional regulation of neurogenesis-related genes in mice models of Parkinson’s disease

Research article

Progranulin regulates neuronal outgrowth independent of Sortilin

Research article

Hyperpolarization-activated cyclic nucleotide gated channels: a potential molecular link between epileptic seizures and Aβ generation in Alzheimer’s disease

Research article

Frataxin deficiency unveils cell-context dependent actions of insulin-like growth factor I on neurons

Research article

IκBα deficiency in brain leads to elevated basal neuroinflammation and attenuated response following traumatic brain injury: implications for functional recovery