Fibroblast growth factor 1 gene-transfected adipose-derived mesenchymal stem cells modulate apoptosis and inflammation in the chronic constriction injury model of neuropathic pain

Document Type : Research article

Authors

1 Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Mashhad, Iran. Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

2 Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

3 Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

4 Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran. Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

5 Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

6 Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.

7 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. Pharmacodynamics and Toxicology Department, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

Background: Stem cell therapy is noted for its clinical effect in the treatment of neuropathic pain. The aim of this study was 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.
Methods: Rats underwent CCI, were treated with AD-MSCs and AD-MSCs FGF1. The involvement of Bax, Bcl2 and caspases 3, the major contributors of apoptosis, and the markers of inflammatory 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.
Results: The ratio of Bax/ Bcl2, cleaved caspases 3, MMP-2, IL-1β, and Iba1 was elevated on day 14, in CCI animals as 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.
Conclusion: These data suggest that the administration of AD-MSCs FGF1 through modulating apoptosis and neuroinflammation could be considered as a promising medicine for the treatment of neuropathic pain.

Graphical Abstract

Fibroblast growth factor 1 gene-transfected adipose-derived mesenchymal stem cells modulate apoptosis and inflammation in the chronic constriction injury model of neuropathic pain

Keywords

References

(1)        Rice AS, Smith BH and Blyth FM. Pain and the global burden of disease. Pain. (2016) 157: 791-6.
(2)        Zhang J-M and An J. Cytokines, inflammation and pain. International anesthesiology clinics. (2007) 45: 27.
(3)        Austin PJ and Moalem Taylor G. The neuro-immune balance in neuropathic pain: involvement of inflammatory immune cells, immune-like glial cells and cytokines. Journal of neuroimmunology. (2010) 229: 26-50.
(4)        Gutiérrez-Fernández M, Rodríguez-Frutos B, Otero-Ortega L, Ramos Cejudo J, Fuentes B and Díez-Tejedor E. Adipose tissue-derived stem cells in stroke treatment: from bench to bedside. Discovery medicine. (2013) 16: 37-43.
(5)        Haico de Gast M, Torrensma B, Fitzgerald E and Stevens H. The Treatment of Chronic Neuropathic Pain: Bio (Regenerative) Pain Treatment through Lipofilling. A Short Communication Case Series. Pain Physician. (2016) 19: E495-E8.
(6)        Kroon E, Martinson LA, Kadoya K, Bang AG, Kelly OG, Eliazer S, Young H, Richardson M, Smart NG and Cunningham J. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nature biotechnology. (2008) 26: 443-52.
(7)        Li X, Gan K, Song G and Wang C. VEGF gene transfected umbilical cord mesenchymal stem cells transplantation improve the lower limb vascular lesions of diabetic rats. Journal of diabetes and its complications. (2015) 29: 872-81.
(8)        Ghazavi H, Hoseini SJ, Ebrahimzadeh-Bideskan A, Mashkani B, Mehri S, Ghorbani A, Sadri K, Mahdipour E, Ghasemi F and Forouzanfar F. Fibroblast Growth Factor Type 1 (FGF1)-Overexpressed Adipose-Derived Mesenchaymal Stem Cells (AD-MSCFGF1) Induce Neuroprotection and Functional Recovery in a Rat Stroke Model. Stem Cell Reviews and Reports. (2017) 1-16.
(9)        Lee HY, Lee H-L, Yun Y, Kim J-S, Ha Y, Yoon DH, Lee S-H and Shin DA. Human adipose stem cells improve mechanical allodynia and enhance functional recovery in a rat model of neuropathic pain. Tissue Engineering Part A. (2015) 21: 2044-52.
(10)      Raju R, Palapetta SM, Sandhya VK, Sahu A, Alipoor A, Balakrishnan L, Advani J, George B, Kini KR, and Geetha N. A network map of FGF-1/FGFR signaling system. Journal of signal transduction. (2014) 2014:
(11)      Hoseini SJ, Ghazavi H, Forouzanfar F, Mashkani B, Ghorbani A, Mahdipour E, Ghasemi F, Sadeghnia HR and Ghayour-Mobarhan M. Fibroblast Growth Factor 1-Transfected Adipose-Derived Mesenchymal Stem Cells Promote Angiogenic Proliferation. DNA and Cell Biology. (2017)
(12)      Forouzanfar F, Amin B, Ghorbani A, Ghazavi H, Ghasemi F, Sadri K, Mehri S, Sadeghnia HR and Hosseinzadeh H. New approach for the treatment of neuropathic pain: Fibroblast growth factor 1 gene-transfected adipose-derived mesenchymal stem cells. Eur J Pain. (2017)
(13)      Ghorbani A, Jalali SA and Varedi M. Isolation of adipose tissue mesenchymal stem cells without tissue destruction: a non-enzymatic method. Tissue and Cell. (2014) 46: 54-8.
(14)      Bennett GJ and Xie Y-K. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. (1988) 33: 87-107.
(15)      Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical biochemistry. (1976) 72: 248-54.
(16)      Martucci C, Trovato AE, Costa B, Borsani E, Franchi S, Magnaghi V, Panerai AE, Rodella LF, Valsecchi AE and Sacerdote P. 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. PAIN®. (2008) 137: 81-95.
(17)      Liu T, Jiang C-Y, Fujita T, Luo S-W and Kumamoto E. Enhancement by interleukin-1β of AMPA and NMDA receptor-mediated currents in adult rat spinal superficial dorsal horn neurons. Molecular pain. (2013) 9: 16.
(18)      Kawasaki Y, Zhang L, Cheng J-K and Ji R-R. 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. Journal of Neuroscience. (2008) 28: 5189-94.
(19)      Brenner GJ, Ji RR, Shaffer S and Woolf CJ. Peripheral noxious stimulation induces phosphorylation of the NMDA receptor NR1 subunit at the PKC‐dependent site, serine‐896, in spinal cord dorsal horn neurons. European Journal of Neuroscience. (2004) 20: 375-84.
(20)      Samad TA, Moore KA, Sapirstein A and Billet S. Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature. (2001) 410: 471.
(21)      Pizzi MA and Crowe MJ. Matrix metalloproteinases and proteoglycans in axonal regeneration. Experimental neurology. (2007) 204: 496-511.
(22)      Lakhan SE and Avramut M. Matrix metalloproteinases in neuropathic pain and migraine: friends, enemies, and therapeutic targets. Pain research and treatment. (2012) 2012:
(23)      Kawasaki Y, Xu Z-Z, Wang X, Park J-Y, Zhuang Z-Y, Tan P-H, Gao Y-J, Roy K, Corfas G and Lo EH. Distinct roles of matrix metalloproteases in the early-and late-phase development of neuropathic pain. Nature medicine. (2008) 14: 331.
(24)      Rahbardar MG, Amin B, Mehri S, Mirnajafi-Zadeh SJ and Hosseinzadeh H. Anti-inflammatory effects of ethanolic extract of Rosmarinus officinalis L. and rosmarinic acid in a rat model of neuropathic pain. Biomedicine & Pharmacotherapy. (2017) 86: 441-9.
(25)      Kocan B, Maziarz A, Tabarkiewicz J, Ochiya T and Banaś-Ząbczyk A. Trophic Activity and Phenotype of Adipose Tissue-Derived Mesenchymal Stem Cells as a Background of Their Regenerative Potential. Stem cells international. (2017) 2017:
(26)      Sacerdote P, Niada S, Franchi S, Arrigoni E, Rossi A, Yenagi V, De Girolamo L, Panerai AE and Brini AT. Systemic administration of human adipose-derived stem cells reverts nociceptive hypersensitivity in an experimental model of neuropathy. Stem cells and development. (2012) 22: 1252-63.
(27)      Siniscalco D, Giordano C, Galderisi U, Luongo L, de Novellis V, Rossi F and Maione S. Long-lasting effects of human mesenchymal stem cell systemic administration on pain-like behaviors, cellular, and biomolecular modifications in neuropathic mice. Front Integr Neurosci. (2011) 5: 79.
(28)      Kuo H-S, Tsai M-J, Huang M-C, Chiu C-W, Tsai C-Y, Lee M-J, Huang W-C, Lin Y-L, Kuo W-C and Cheng H. Acid fibroblast growth factor and peripheral nerve grafts regulate Th2 cytokine expression, macrophage activation, polyamine synthesis, and neurotrophin expression in transected rat spinal cords. Journal of Neuroscience. (2011) 31: 4137-47.
(29)      Cai D, Deng K, Mellado W, Lee J, Ratan RR and Filbin MT. Arginase I and polyamines act downstream from cyclic AMP in overcoming inhibition of axonal growth MAG and myelin in vitro. Neuron. (2002) 35: 711-9.
(30)      Lin Y-L, Kuo H-S, Lo M-J, Tsai M-J, Lee M-J, Huang W-C, Kuo W-C, Shih Y-H, Cheng H and Huang M-C. Treatment with nerve grafts and aFGF attenuates allodynia caused by cervical root transection injuries. Restorative neurology and neuroscience. (2011) 29: 265-74.
(31)      Siniscalco D, Giordano C, Fuccio C, Luongo L, Ferraraccio F, Rossi F, de Novellis V, Roth KA and Maione S. Involvement of subtype 1 metabotropic glutamate receptors in apoptosis and caspase-7 over-expression in spinal cord of neuropathic rats. Pharmacological research. (2008) 57: 223-33.
(32)      de Novellis V, Siniscalco D, Galderisi U, Fuccio C, Nolano M, Santoro L, Cascino A, Roth KA, Rossi F and Maione S. 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. Neuropharmacology. (2004) 46: 468-79.
(33)      Delmas E, Jah N, Pirou C, Bouleau S, Le Floch N, Vayssière J, Mignotte B and Renaud F. FGF1 C-terminal domain and phosphorylation regulate intracrine FGF1 signaling for its neurotrophic and anti-apoptotic activities. Cell death & disease. (2016) 7: e2079.
(34)      Rodriguez-Enfedaque A, Bouleau S, Laurent M, Courtois Y, Mignotte B, Vayssière J-L and Renaud F. FGF1 nuclear translocation is required for both its neurotrophic activity and its p53-dependent apoptosis protection. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. (2009) 1793: 1719-27.
(35)      Bouleau S, Grimal H, Rincheval V, Godefroy N, Mignotte B, Vayssiere J-L and Renaud F. FGF1 inhibits p53-dependent apoptosis and cell cycle arrest via an intracrine pathway. Oncogene. (2005) 24: 7839.
Iranian Journal of Pharmaceutical Research
Volume 19, Issue 4
Autumn 2020
Pages 151-159

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