Fibroblast Growth Factor 1 Gene-Transfected Adipose-Derived Mesenchymal Stem Cells Modulate Apoptosis And Inflammation In The Chronic Constriction Injury Model of Neuropathic Pain

Stem cell therapy is noted for its clinical effect in the treatment of neuropathic pain. This study aimed to investigate the potential anti-apoptotic and anti-inflammatory effects of adipose-derived mesenchymal stem cells (AD-MSCs) and fibroblast growth factor 1 gene-transfected adipose-derived mesenchymal stem cells (AD-MSCs FGF1) on chronic constriction injury (CCI) of the rat’s sciatic nerve. The rats that underwent CCI were treated with AD-MSCs and AD-MSCs FGF1. Bax, Bcl2, and caspases 3, the major contributors of apoptosis, and inflammatory markers including Iba-1, IL1-β, and MMP-2 were evaluated in the lumbar portion (L4-L6) of the spinal cord through western bloating at days 3 and 14. The ratio of Bax/Bcl2, cleaved caspases 3, MMP-2, IL-1β, and Iba1, was elevated in CCI animals compared to sham-operated animals and decreased following treatment with both AD-MSCs and AD-MSCs FGF1. However, the effect of AD-MSCs FGF1 was significantly higher than AD-MSCs. These data suggest that the administration of AD-MSCs FGF1 through modulating apoptosis and neuroinflammation could be considered a promising medicine for treating neuropathic pain.

[1]  H. Sadeghnia,et al.  New approach for the treatment of neuropathic pain: Fibroblast growth factor 1 gene‐transfected adipose‐derived mesenchymal stem cells , 2018, European journal of pain.

[2]  T. Ochiya,et al.  Trophic Activity and Phenotype of Adipose Tissue-Derived Mesenchymal Stem Cells as a Background of Their Regenerative Potential , 2017, Stem cells international.

[3]  M. Ghayour-Mobarhan,et al.  Fibroblast Growth Factor 1-Transfected Adipose-Derived Mesenchymal Stem Cells Promote Angiogenic Proliferation. , 2017, DNA and cell biology.

[4]  H. Hosseinzadeh,et al.  Anti-inflammatory effects of ethanolic extract of Rosmarinus officinalis L. and rosmarinic acid in a rat model of neuropathic pain. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[5]  Andrew S.C. Rice,et al.  Pain and the global burden of disease , 2016, Pain.

[6]  H. D. de Gast,et al.  The Treatment of Chronic Neuropathic Pain: Bio (Regenerative) Pain Treatment through Lipofilling. A Short Communication Case Series. , 2016, Pain physician.

[7]  B. Mignotte,et al.  FGF1 C-terminal domain and phosphorylation regulate intracrine FGF1 signaling for its neurotrophic and anti-apoptotic activities , 2016, Cell Death and Disease.

[8]  G. Song,et al.  VEGF gene transfected umbilical cord mesenchymal stem cells transplantation improve the lower limb vascular lesions of diabetic rats. , 2015, Journal of diabetes and its complications.

[9]  D. Yoon,et al.  Human Adipose Stem Cells Improve Mechanical Allodynia and Enhance Functional Recovery in a Rat Model of Neuropathic Pain. , 2015, Tissue engineering. Part A.

[10]  Linyi Chen,et al.  A Network Map of FGF-1/FGFR Signaling System , 2014, Journal of signal transduction.

[11]  M. Varedi,et al.  Isolation of adipose tissue mesenchymal stem cells without tissue destruction: a non-enzymatic method. , 2014, Tissue & cell.

[12]  M. Gutiérrez-Fernández,et al.  Adipose tissue-derived stem cells in stroke treatment: from bench to bedside. , 2013, Discovery medicine.

[13]  P. Sacerdote,et al.  Systemic administration of human adipose-derived stem cells reverts nociceptive hypersensitivity in an experimental model of neuropathy. , 2013, Stem cells and development.

[14]  E. Kumamoto,et al.  Enhancement by interleukin-1β of AMPA and NMDA receptor-mediated currents in adult rat spinal superficial dorsal horn neurons , 2013, Molecular pain.

[15]  S. Lakhan,et al.  Matrix Metalloproteinases in Neuropathic Pain and Migraine: Friends, Enemies, and Therapeutic Targets , 2012, Pain research and treatment.

[16]  D. Siniscalco,et al.  Long-Lasting Effects of Human Mesenchymal Stem Cell Systemic Administration on Pain-Like Behaviors, Cellular, and Biomolecular Modifications in Neuropathic Mice , 2011, Front. Integr. Neurosci..

[17]  Meng-Jen Lee,et al.  Acid Fibroblast Growth Factor and Peripheral Nerve Grafts Regulate Th2 Cytokine Expression, Macrophage Activation, Polyamine Synthesis, and Neurotrophin Expression in Transected Rat Spinal Cords , 2011, The Journal of Neuroscience.

[18]  Ming-Chao Huang,et al.  Treatment with nerve grafts and aFGF attenuates allodynia caused by cervical root transection injuries. , 2011, Restorative neurology and neuroscience.

[19]  Gila Moalem-Taylor,et al.  The neuro-immune balance in neuropathic pain: Involvement of inflammatory immune cells, immune-like glial cells and cytokines , 2010, Journal of Neuroimmunology.

[20]  R. Kizek,et al.  Matrix metalloproteinases. , 2010, Current medicinal chemistry.

[21]  Y. Courtois,et al.  FGF1 nuclear translocation is required for both its neurotrophic activity and its p53-dependent apoptosis protection. , 2009, Biochimica et biophysica acta.

[22]  L. Rodella,et al.  The purinergic antagonist PPADS reduces pain related behaviours and interleukin-1β, interleukin-6, iNOS and nNOS overproduction in central and peripheral nervous system after peripheral neuropathy in mice , 2008, PAIN®.

[23]  R. Ji,et al.  Cytokine Mechanisms of Central Sensitization: Distinct and Overlapping Role of Interleukin-1β, Interleukin-6, and Tumor Necrosis Factor-α in Regulating Synaptic and Neuronal Activity in the Superficial Spinal Cord , 2008, The Journal of Neuroscience.

[24]  D. Siniscalco,et al.  Involvement of subtype 1 metabotropic glutamate receptors in apoptosis and caspase-7 over-expression in spinal cord of neuropathic rats. , 2008, Pharmacological research.

[25]  Ping-Heng Tan,et al.  Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain , 2008, Nature Medicine.

[26]  E. Kroon,et al.  Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo , 2008, Nature Biotechnology.

[27]  M. Pizzi,et al.  Matrix metalloproteinases and proteoglycans in axonal regeneration , 2007, Experimental Neurology.

[28]  Jun-Ming Zhang,et al.  Cytokines, Inflammation, and Pain , 2007, International anesthesiology clinics.

[29]  B. Mignotte,et al.  FGF1 inhibits p53-dependent apoptosis and cell cycle arrest via an intracrine pathway , 2005, Oncogene.

[30]  C. Woolf,et al.  Peripheral noxious stimulation induces phosphorylation of the NMDA receptor NR1 subunit at the PKC‐dependent site, serine‐896, in spinal cord dorsal horn neurons , 2004, The European journal of neuroscience.

[31]  L. Santoro,et al.  Blockade of glutamate mGlu5 receptors in a rat model of neuropathic pain prevents early over-expression of pro-apoptotic genes and morphological changes in dorsal horn lamina II , 2004, Neuropharmacology.

[32]  W. Mellado,et al.  Arginase I and Polyamines Act Downstream from Cyclic AMP in Overcoming Inhibition of Axonal Growth MAG and Myelin In Vitro , 2002, Neuron.

[33]  Adam Sapirstein,et al.  Interleukin-1β-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity , 2001, Nature.

[34]  Gary J. Bennett,et al.  A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man , 1988, Pain.

[35]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.