Transplantation of Schwann cells co-cultured with brain-derived neurotrophic factor for the treatment of experimental autoimmune neuritis
Introduction
Guillain–Barré syndrome (GBS) is a common paralytic disease in healthy adults with a prevalence of 1–4/100,000 (Vucic et al., 2009). Plasma exchange (PE) and intravenous immunoglobulin (IVIg) are the most effective treatments for GBS at present. Although PE and IVIg shorten the duration of GBS, 4–15% of patients die, and up to 20% of patients are left disabled despite modern treatment (Rees et al., 1998, Visser et al., 1999). Therefore, further research is needed to find ways to prevent the 20% of patients from being left with continuous disability and a better or cocktail therapy may be explored.
Experimental autoimmune neuritis (EAN) is a widely used animal model of GBS (Maurer and Gold, 2002). In 2007, the first therapy for EAN with cell transplantation was performed by Xu et al. (Xu et al., 2007). This study initiated new ideas for the treatment of EAN with cell transplantation.
Many neurons in the peripheral nervous system (PNS) are insulated with a myelin sheath formed by Schwann cells surrounding the axons. During nerve regeneration, SCs regulate demyelination through their connection with axons (Jessen and Mirsky, 1999). After peripheral nerve injury, SCs proliferate to scavenge the dead cells together with macrophages. During these processes, several neurotrophic factors are produced to facilitate nerve regeneration (Syroid et al., 1996, Murwani and Armati, 1998). Currently, SCs are widely used as seed cells in tissue engineering. Brain derived neurotrophic factor (BDNF) plays an important role in neuron degeneration and regeneration. Some studies have shown that BDNF can promote the survival of SCs in vitro through inhibition of apoptosis. Therefore, the treatment of SCs in vitro with suitable neurotrophic factors may improve the survival of transplanted SCs. In this study, we exposed cultured SCs to BDNF and then transplanted the SCs into rats to investigate their effects on EAN.
Section snippets
Isolation and characterization of SCs
Under aseptic conditions, the epineurium was dissected bilaterally from the sciatic nerves in neonatal SD rats (4–6 days after birth). SCs were cultured and passaged based on the method used by Qin et al. (Qin et al., 2012). Cells of passage 3 were plated onto glass coverslips in 24-well plates and incubated in a 5% CO2 incubator at 37 °C for 24 h. Then, the cultures were fixed (30 min, 4% paraformaldehyde in PBS) and stoved at 37 °C. The cells were washed in PBS for 3 times and then treated with 1
Characterization of SCs
SCs could be visualized by immunohistochemistry using antibodies against S-100. They grew in a shoulder-to-shoulder and head-to-head manner. After DAB staining, SCs stained brown when observed under a phase contrast microscope (Fig. 1. A).
Determination of the optimal concentration of BDNF
After stimulation with different concentrations of BDNF, the proliferation of SCs was detected with a MTT assay. A concentration of 50 ng/mL induced the highest proliferation activity of SCs (Fig. 1. B). Furthermore, after a 24 h-stimulation, the peak NGF and
Discussion
Recently, a report from Zujovic V (Zujovic et al., 2012) has demonstrated a striking therapeutic effect of SCs in DA rats with MOG-induced EAE (a model of MS). By contrast, we have shown that allogenic SCs, transplanted into Lewis rats with P2 57–81 peptide-induced EAN at the acute phase of disease, do not lead to any distinguished neurological, histopathological improvement or expression change of CD11a, CCL3, NGF and S-100 mRNA in sciatic nerves, despite exogenous SCs injected through
Conflict of interest
The authors declare that they have no conflict of interest.
Acknowledgments
This study was supported by the Natural Science Foundation of China (project number: 30901331) and Heilongjiang youth science fund (project number: QC2009C21).
References (20)
- et al.
Schwann cells and their precursors emerge as major regulators of nerve development
Trends Neurosci.
(1999) - et al.
Brain-derived neurotrophic factor suppresses anoikis-induced death of Schwann cells
Neurosci. Lett.
(2008) - et al.
Peripheral nerve fibroblasts as a source of IL-6, TNFalpha and IL-1 and their modulation by IFNgamma
J. Neurol. Sci.
(1998) - et al.
Guillain-Barre syndrome: an update
J. Clin. Neurosci.
(2009) - et al.
Suppression of chronic experimental autoimmune neuritis by nasally administered recombinant rat interleukin-6
Immunology
(1999) - et al.
Mesenchymal stem cells effectively modulate pathogenic immune response in experimental autoimmune encephalomyelitis
Ann. Neurol.
(2007) - et al.
Extensive cell migration, axon regeneration, and improved function with polysialic acid-modified Schwann cells after spinal cord injury
Glia
(2012) - et al.
Pathogenesis of chronic inflammatory demyelinating polyradiculoneuropathy
J. Peripher. Nerv. Syst.
(2006) - et al.
Animal models of immune-mediated neuropathies
Curr. Opin. Neurol.
(2002) - et al.
The role of macrophage inflammatory protein-1 alpha/CCL3 in regulation of T cell-mediated immunity to Cryptococcus neoformans infection
J. Immunol.
(2000)
Cited by (10)
2,4-Dinitrophenol does not exert neuro-regenerative potential in experimental autoimmune neuritis
2023, Neuroscience LettersA comparative morphological, electrophysiological and functional analysis of axon regeneration through peripheral nerve autografts genetically modified to overexpress BDNF, CNTF, GDNF, NGF, NT3 or VEGF
2014, Experimental NeurologyCitation Excerpt :Schwann cells express p75, a low-affinity receptor for all neurotrophins, trkB (Frisén et al., 1993), ret1/GDNFRalpha1 (Hase et al., 2005) and trkC, the receptor for NT3 (Cosgaya et al., 2002). BDNF and GDNF promote the proliferation of cultured Schwann cells in vitro (Hou et al., 2013) and GDNF induced Schwann cell proliferation in intact sciatic nerves (Höke et al., 2003). Interestingly, Schwann cell proliferation was not observed in chronically denervated autografts transduced with LV-GDNF.
Melatonin promotes Schwann cell proliferation and migration via the shh signalling pathway after peripheral nerve injury
2021, European Journal of NeuroscienceEffect of mycobacterium leprae on neurotrophins expression in human schwann cells and mouse sciatic nerves
2020, Memorias do Instituto Oswaldo CruzImmunomodulatory and anti-oxidative effect of the direct TRPV1 receptor agonist capsaicin on Schwann cells
2020, Journal of Neuroinflammation