New approach for the treatment of neuropathic pain: Fibroblast growth factor 1 gene-transfected adipose-derived mesenchymal stem cells

被引:35
|
作者
Forouzanfar, F. [1 ]
Amin, B. [2 ]
Ghorbani, A. [3 ]
Ghazavi, H. [4 ]
Ghasemi, F. [5 ]
Sadri, K. [6 ]
Mehri, S. [7 ]
Sadeghnia, H. R. [1 ,8 ]
Hosseinzadeh, H. [7 ]
机构
[1] Mashhad Univ Med Sci, Dept Pharmacol, Fac Med, Mashhad, Iran
[2] Sabzevar Univ Med Sci, Dept Physiol & Pharmacol, Cellular & Mol Res Ctr, Fac Med, Sabzevar, Iran
[3] Mashhad Univ Med Sci, Pharmacol Res Ctr Med Plants, Mashhad, Iran
[4] Mashhad Univ Med Sci, Dept Med Biotechnol, Fac Med, Mashhad, Iran
[5] Arak Univ Med Sci, Dept Med Biotechnol, Fac Med, Arak, Iran
[6] Mashhad Univ Med Sci, Nucl Med Res Ctr, Mashhad, Iran
[7] Mashhad Univ Med Sci, Sch Pharm, Pharmacodynamy & Toxicol Dept, Pharmaceut Res Ctr, Mashhad, Iran
[8] Mashhad Univ Med Sci, Div Neurocognit Sci, Psychiat & Behav Sci Res Ctr, Mashhad, Iran
关键词
FIBROBLAST-GROWTH-FACTOR; CHRONIC CONSTRICTION INJURY; SPINAL-CORD-INJURY; SUPERFICIAL DORSAL HORN; PERIPHERAL-NERVE GRAFTS; STROMAL CELLS; RAT MODEL; MECHANICAL ALLODYNIA; ETHANOLIC EXTRACTS; SENSITIVE METHOD;
D O I
10.1002/ejp.1119
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
BackgroundNeuropathic pain triggered by peripheral nerve lesion is extremely difficult to manage with current approaches, hence the importance of exploring therapeutic alternatives. MethodsWe have analysed 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). The mechanical and thermal hypersensitivity were assessed using the von Frey filament, radiant heat and acetone drop tests. Histopathological and apoptotic changes and the level of FGF1, GFAP and TNF proteins were assessed in the lumbar portion (L4-L6). Moreover, AD-MSCs (FGF1) were labelled with Tc-99m -HMPAO and isolated organ counting were performed upon AD-MSCs (FGF1) administration. ResultsAdministration of AD-MSCs (FGF1) attenuated the CCI-induced mechanical and thermal hypersensitivity. Spinal structural alterations and apoptosis were decreased in the AD-MSCs (FGF1) group. The injection of either phosphate-buffered saline or normal NIH3T3 fibroblasts could not attenuate the behavioural symptoms of neuropathic pain. Increased genetically engineered cells were counted in the injured sciatic nerve and the elevated levels of FGF1 were detected in the spinal tissue. Stem cell therapy lead to decrement the level of the CCI-induced TNF- and GFAP expression. ConclusionThe intravenous administration of AD-MSCs (FGF1) could be considered as a potential remedy for the management of neuropathic pain. SignificanceAD-MSCs (FGF1) attenuated the CCI-induced mechanical and thermal hypersensitivity. Spinal structural alterations and apoptosis were significantly decreased in the AD-MSCs (FGF1) group. Elevated levels of FGF1 were detected in the spinal tissue.
引用
收藏
页码:295 / 310
页数:16
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