Intrathecal Injection of SIRT1-modified Human Mesenchymal Stem Cells Alleviates Neuropathic Pain in Rat

Tian, Jie; Song, Tieying; Wang, Hong; Wang, Wenli; Zhang, Zaiwang; Yan, Ruyu; Ma, Xiaojing; Hu, Yue

doi:10.1007/s12031-020-01717-2

Cited by 14 publications

(15 citation statements)

References 41 publications

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“…In contrast to the sham group, the NAD content was lower and the NAM content was higher in CCI mice, which was consistent with the difference in SIRT1 levels 52 . Additionally, compared with human bone marrow mesenchymal stem cell (hMSC)‐control implantation, intrathecal injection of hMSCs overexpressing SIRT1 (hMSCs‐SIRT1) exerted superior effects on alleviating neuropathic pain in CCI rats by reducing proinflammatory cytokine levels in the serum and spinal dorsal horn 17 . These results indicate that SIRT1 may be involved in the development of neuropathic pain following CCI.…”

Section: Sirt1 and Neuropathic Painsupporting

confidence: 62%

“…Under physiological conditions, SIRT1 is present in the nucleus and cytoplasm and acts mainly in the nucleus to deacetylate transcription factors such as peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α), p53, forkhead box O, and nuclear factor‐kappa B (NF‐κB) 16 . Growing evidence has shown that SIRT1 plays an important role in reducing inflammation and oxidative stress and in improving mitochondrial function 17‐19 . Thus, SIRT1 may be a promising therapeutic target in the treatment of chronic pain.…”

Section: Introductionmentioning

confidence: 99%

“…16 Growing evidence has shown that SIRT1 plays an important role in reducing inflammation and oxidative stress and in improving mitochondrial function. [17][18][19] Thus, SIRT1 may be a promising therapeutic target in the treatment of chronic pain.…”

mentioning

confidence: 99%

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SIRT1: A promising therapeutic target for chronic pain

et al. 2022

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Chronic pain remains an unresolved problem. Current treatments have limited efficacy. Thus, novel therapeutic targets are urgently required for the development of more effective analgesics. An increasing number of studies have proved that sirtuin 1 (SIRT1) agonists can relieve chronic pain. In this review, we summarize recent progress in understanding the roles and mechanisms of SIRT1 in mediating chronic pain associated with peripheral nerve injury, chemotherapy‐induced peripheral neuropathy, spinal cord injury, bone cancer, and complete Freund's adjuvant injection. Emerging studies have indicated that SIRT1 activation may exert positive effects on chronic pain relief by regulating inflammation, oxidative stress, and mitochondrial dysfunction. Therefore, SIRT1 agonists may serve as potential therapeutic drugs for chronic pain.

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Section: Sirt1 and Neuropathic Painsupporting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

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SIRT1: A promising therapeutic target for chronic pain

et al. 2022

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“…In general, eight administration methods have been proposed for applying MSCs. These methods include intravenous injection (IV) [ 95 , 96 ], intra-arterial injection (IA) [ 97 , 98 ], intrathecal injection (IT) [ 99 , 100 ], intracardiac injection (IC) [ 101 ], intra-articular injection (IAT) [ 102 , 103 ], intramuscular injection (IM) [ 104 ], intraosseous injection (IO) [ 105 ], and implant for cells incorporated into a matrix or an implanted device [ 106 , 107 ]. According to the study on the clinical trials of MSCs over 2014-2018, the most common administration method used in clinical trials was IV.…”

Section: Approaches For Applying Mscsmentioning

confidence: 99%

The Clinical Trials of Mesenchymal Stromal Cells Therapy

Kouchakian

Baghban

Moniri

et al. 2021

Stem Cells International

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Mesenchymal stromal cells (MSCs) are a heterogeneous population of adult stem cells, which are multipotent and possess the ability to differentiate/transdifferentiate into mesodermal and nonmesodermal cell lineages. MSCs display broad immunomodulatory properties since they are capable of secreting growth factors and chemotactic cytokines. Safety, accessibility, and isolation from patients without ethical concern make MSCs valuable sources for cell therapy approaches in autoimmune, inflammatory, and degenerative diseases. Many studies have been conducted on the application of MSCs as a new therapy, but it seems that a low percentage of them is related to clinical trials, especially completed clinical trials. Considering the importance of clinical trials to develop this type of therapy as a new treatment, the current paper is aimed at describing characteristics of MSCs and reviewing relevant clinical studies registered on the NIH database during 2016-2020 to discuss recent advances on MSC-based therapeutic approaches being used in different diseases.

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“…Another advantage is that CSF space offers a large surface area of CNS for stem cells to migrate into parenchyma or act through the release of trophic factors. The feasibility, reproducibility, and safety of intrathecal stem cell delivery have been proven in small animals [ 7 ], large animals [ 8 ], and clinical settings [ 9 ]. However, the challenge with intrathecal injection is that the cells infused as a suspension are subject to sedimentation and may drain away from the injection site.…”

Section: Introductionmentioning

confidence: 99%

Two in One: Use of Divalent Manganese Ions as Both Cross-Linking and MRI Contrast Agent for Intrathecal Injection of Hydrogel-Embedded Stem Cells

et al. 2021

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Cell therapy is a promising tool for treating central nervous system (CNS) disorders; though, the translational efforts are plagued by ineffective delivery methods. Due to the large contact surface with CNS and relatively easy access, the intrathecal route of administration is attractive in extensive or global diseases such as stroke or amyotrophic lateral sclerosis (ALS). However, the precision and efficacy of this approach are still a challenge. Hydrogels were introduced to minimize cell sedimentation and improve cell viability. At the same time, contrast agents were integrated to allow image-guided injection. Here, we report using manganese ions (Mn2+) as a dual agent for cross-linking alginate-based hydrogels and magnetic resonance imaging (MRI). We performed in vitro studies to test the Mn2+ alginate hydrogel formulations for biocompatibility, injectability, MRI signal retention time, and effect on cell viability. The selected formulation was injected intrathecally into pigs under MRI control. The biocompatibility test showed a lack of immune response, and cells suspended in the hydrogel showed greater viability than monolayer culture. Moreover, Mn2+-labeled hydrogel produced a strong T1 MRI signal, which enabled MRI-guided procedure. We confirmed the utility of Mn2+ alginate hydrogel as a carrier for cells in large animals and a contrast agent at the same time.

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Intrathecal Injection of SIRT1-modified Human Mesenchymal Stem Cells Alleviates Neuropathic Pain in Rat

Cited by 14 publications

References 41 publications

SIRT1: A promising therapeutic target for chronic pain

SIRT1: A promising therapeutic target for chronic pain

The Clinical Trials of Mesenchymal Stromal Cells Therapy

Two in One: Use of Divalent Manganese Ions as Both Cross-Linking and MRI Contrast Agent for Intrathecal Injection of Hydrogel-Embedded Stem Cells

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