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

Forouzanfar, Fatemeh; Amin, Bahareh; Ghorbani, Ahmad; Ghazavi, Hamed; Ghasemi, Faezeh; Sadri, Kayvan; Mehri, Soghra; Sadeghnia, Hamidreza; Hosseinzadeh, Hossein

doi:10.1002/ejp.1119

Cited by 49 publications

(39 citation statements)

References 90 publications

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“…After mounting, a 5 μm section of each tissue was prepared and then stained with H&E. Histopathological changes were then investigated and blindly scored by a pathologist. 21,22…”

Section: Histopathological Examinationmentioning

confidence: 99%

<p>Antioxidant and toxicity studies of biosynthesized cerium oxide nanoparticles in rats</p>

Khorrami

Sadeghnia

Pasdar

et al. 2019

IJN

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Purpose The purpose of this study was to investigate the acute toxic potential of cerium oxide nanoparticles (CNPs) synthesized by pullulan in adult male Wistar rats. Patients and methods Thirty male Wistar rats randomly were divided into five experimental groups of six animals each. The animals were received 50, 100, 200, and 400 mg/kg CNPs for 14 consecutive days. At the end of the experiment, the rats were euthanized and histopathological evaluation of the liver and renal tissues, as well ass, the markers of serum oxidative stress including thiobarbituric acid reactive substances, total sulfhydryl content, and antioxidant capacity (using ferric reducing/antioxidant power assay) were assessed. Hematological parameters and the activity of liver function enzymes were also measured. Results The results of this study showed that CNPs caused no significant changes in the activity of liver enzymes, hepatic and renal histopathology and hematological parameters, while significantly improved serum redox status. Conclusion Acute administration of pullulan-mediated CNPs is safe and possess antioxidant activity.

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“…After mounting, a 5 μm section of each tissue was prepared and then stained with H&E. Histopathological changes were then investigated and blindly scored by a pathologist. 21,22…”

Section: Histopathological Examinationmentioning

confidence: 99%

<p>Antioxidant and toxicity studies of biosynthesized cerium oxide nanoparticles in rats</p>

Khorrami

Sadeghnia

Pasdar

et al. 2019

IJN

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“…Studies have shown that fibroblast growth factor (38,39) and hepatocyte growth factor (40,41) can reduce pain by inhibiting the activation of astrocytes in the spinal cord; and PRP contains various growth factors, including fibroblast growth factor and hepatocyte growth factor (42), so a longterm higher concentration of PRP acts on cells or may make such inhibitory effects more obvious Traditional studies have suggested that peripheral and central sensitization causes chronic pain due to changes in neuronal plasticity. However, recent studies have found that glial cells, especially astrocytes, play an essential role in maintaining chronic pain (43,44).…”

Section: Discussionmentioning

confidence: 99%

Platelet-rich plasma improves chronic inflammatory pain by inhibiting PKM2-mediated aerobic glycolysis in astrocytes

Wei¹,

Jin²,

Meng³

et al. 2020

Ann Transl Med

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Background: Astrocytes are highly glycolytic cells that play a crucial role in chronic pain. Recently it has been found that inflammation and metabolism are related to the inflammatory stimuli closely that cause cellular metabolic changes. Pyruvate kinase M2 (PKM2) is a critical metabolic kinase in aerobic glycolysis or the Warburg effect. Besides, it also plays a crucial role in cell proliferation and signal transduction, but its role in astrocytes is still unclear. Methods:The chronic inflammatory pain model was set up by intraplantar injection of complete Freund's adjuvant (CFA) in Sprague Dawley (SD) rats as well as the cell model was constructed by lipopolysaccharidetreated primary astrocytes. Von Frey filament stimulation was used to continuously observe the changes of pain behavior in rats after modeling. Then, immunofluorescence staining and Western blot tests were used to observe the expression levels of glial fibrillary acidic protein (GFAP), pyruvate kinase (PKM2), signal transducers and activators of transcription 3 (STAT3) and high mobility group box-1 protein (HMGB1).After that, specific kits measured lactate contents. Finally, we observed the platelet-rich plasma's (PRP) effect on mechanical hyperalgesia in rats with inflammatory pain induced by CFA and its effect on related signal molecules.Results: We found that in the CFA-induced inflammatory pain model, astrocytes were significantly activated, GFAP was increased, PKM2 was significantly up-regulated, and the glycolytic product lactate was increased. Also, intrathecal injection of PRP increased the pain threshold, inhibited the activation of astrocytes, and decreased the expression of PKM2 and aerobic glycolysis; in LPS-activated primary astrocytes as an in vitro model, we found PKM2 translocation activationSTAT3 signaling resulted in sustained activation of astrocyte marker GFAP, and the expression level and localization of p-STAT3 were correlated with PKM2. PRP could inhibit the activation of astrocytes, reduce the expression of PKM2 and the expression levels of glycolysis and GFAP, GLUT1, and p-STAT3 in astrocytes.Conclusions: Our findings suggest PKM2 not only plays a glycolytic role in astrocytes, but also plays a crucial role in astrocyte-activated signaling pathways, and PRP attenuates CFA induced inflammatory pain by inhibiting aerobic glycolysis in astrocytes, providing a new therapeutic target for the treatment of inflammatory pain.

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“…The experimental n was determined based on previous literature data [23,39,40]. The n per group is indicated in legends.…”

Section: Ethical Concernsmentioning

confidence: 99%

“…The CCI animals received SCAP topically (10 6 cells reconstituted in 200 mL of PBS; treated group), or 200 mL of PBS (control group) at the surgery site, around the sciatic nerve on day 0. The dose and route of administration of SCAP were determined based on prior publications [22][23][24][25]. Mechanical hyperalgesia, radiant heat hyperalgesia, and cold allodynia were assessed before (day -3; basal) and at days 3, 7, 14, and 21 after surgery.…”

Section: Neurite Quantificationmentioning

confidence: 99%

“…Literature data showed that local implantation, intravenous or intraperitoneal administration of MSCs, from different sources, trigger potential regenerative effects in preclinical models of peripheral nerve injury [22][23][24][25][26]. Ullah et al demonstrated that transplantation of human dental pulp-derived stem cells into a fibrin glue scaffold ameliorated nerve regeneration in rats [27].…”

Section: Introductionmentioning

confidence: 99%

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Neural Regenerative Potential of Stem Cells Derived from the Tooth Apical Papilla

Dagnino

Chagastelles

Medeiros

et al. 2020

Stem Cells and Development

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The regenerative effects of stem cells derived from dental tissues have been previously investigated. This study assessed the potential of human tooth stem cells from apical papilla (SCAP) on nerve regeneration. The SCAP collected from nine individuals were characterized and polarized by exposure to interferon-g (IFN-g). IFN-g increased kynurenine and interleukin-6 (IL-6) production by SCAP, without affecting the cell viability. IFN-gprimed SCAP exhibited a decrease of brain-derived neurotrophic factor (BDNF) mRNA levels, followed by an upregulation of glial cell-derived neurotrophic factor mRNA. Ex vivo, the co-culture of SCAP with neurons isolated from the rat dorsal root ganglion induced neurite outgrowth, accompanied by increased BDNF secretion, irrespective of IFN-g priming. In vivo, the local application of SCAP reduced the mechanical and thermal hypersensitivity in Wistar rats that had been submitted to sciatic chronic constriction injury. The SCAP also reduced the pain scores, according to the evaluation of the Grimace scale, partially restoring the myelin damage and BDNF immunopositivity secondary to nerve lesion. Altogether, our results provide novel evidence about the regenerative effects of human SCAP, indicating their potential to handle nerve injury-related complications.

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

Abstract: AD-MSCs attenuated the CCI-induced mechanical and thermal hypersensitivity. Spinal structural alterations and apoptosis were significantly decreased in the AD-MSCs group. Elevated levels of FGF1 were detected in the spinal tissue.

Cited by 49 publications

References 90 publications

<p>Antioxidant and toxicity studies of biosynthesized cerium oxide nanoparticles in rats</p>

<p>Antioxidant and toxicity studies of biosynthesized cerium oxide nanoparticles in rats</p>

Platelet-rich plasma improves chronic inflammatory pain by inhibiting PKM2-mediated aerobic glycolysis in astrocytes

Neural Regenerative Potential of Stem Cells Derived from the Tooth Apical Papilla

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