Intrathecal bone marrow stromal cells inhibit neuropathic pain via TGF-β secretion

Chen, Gang; Xie, Rou‐Gang; Ji, Ru-Rong

doi:10.1172/jci80883

Cited by 186 publications

(266 citation statements)

References 58 publications

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“…Previous studies have shown that bone marrow stromal cells can produce long-lasting pain relief in the rat model [13, 14]. The present study shows that the generation of iTH + cells from MSC may also be suitable to achieve long-lasting antinociception, and as shown for the CIA model, to achieve an anti-inflammatory effect.…”

Section: Discussionsupporting

confidence: 64%

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A Promising New Approach for the Treatment of Inflammatory Pain: Transfer of Stem Cell-Derived Tyrosine Hydroxylase-Positive Cells

Ebbinghaus

Jenei-Lanzl

Banchet

et al. 2018

Neuroimmunomodulation

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Objectives: The appearance of endogenous tyrosine hydroxylase-positive cells (TH⁺ cells) in collagen-induced arthritis was associated with an anti-inflammatory effect. Here we investigated putative anti-inflammatory and antinociceptive effects of the transfer of induced, bone marrow stem cell-derived TH⁺ cells (iTH⁺ cells) on murine antigen-induced arthritis (AIA). Methods: Bone marrow-derived stem cells were differentiated into iTH⁺ cells. These cells were transferred to mice immunized against methylated bovine serum albumin (mBSA) 2 days before AIA was induced by injection of mBSA into one knee joint. In AIA control mice and iTH⁺-treated mice the severity of AIA, pain-related behavior, humoral and cellular responses, and the invasion of macrophages into the dorsal root ganglia were assessed. Results: The intravenous transfer of iTH⁺ cells before AIA induction did not cause a sustained suppression of AIA severity but significantly reduced inflammation-evoked pain-related behavior. The iTH⁺ cells used for transfer exhibited enormous production of interleukin-4. A major difference between AIA control mice and iTH⁺-treated AIA mice was a massive invasion of the dorsal root ganglia by iNOS-negative, arginine 1-positive macrophages corresponding to an M2 phenotype. The differences in other cellular and humoral immune parameters such as release of cytokines from stimulated lymphocytes between AIA control mice and iTH⁺-treated mice were small. Conclusions: The transfer of iTH⁺ cells may cause a long-lasting reduction of arthritis-induced pain even if it does not ameliorate inflammation. The invasion of M2 macrophages into the dorsal root ganglia is likely to be an important mechanism of antinociception.

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Section: Discussionsupporting

confidence: 64%

“…However, it has been shown that bone marrow stromal cells produce long-term pain relief in rat models of persistent pain [13] and that intrathecal bone marrow stromal cells inhibit neuropathic pain via TGF-β 1 secretion [14]. Thus, suitable cells seem to have the potential to evoke an antinociceptive effect.…”

Section: Introductionmentioning

confidence: 99%

A Promising New Approach for the Treatment of Inflammatory Pain: Transfer of Stem Cell-Derived Tyrosine Hydroxylase-Positive Cells

Ebbinghaus

Jenei-Lanzl

Banchet

et al. 2018

Neuroimmunomodulation

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“…This intracellular "GABA-glutamate-glutamine cycle" is maintained for normal physiological homeostasis. Hyperexcitable neurons and and its important role in nerve healing and regeneration (33,34), and considering the valuable effect of grow factors such as TGF-β1, alleviating early-and late-phase neuropathic pain symptoms, such as allodynia and hyperalgesia (17).…”

Section: Alterations Of the Gamma Aminobutiric Acid (Gaba) Inhibitionmentioning

confidence: 99%

“…Thus, there is no current "effective" evidence-based scheme in treating NP. Recent in-vitro and animal research has demonstrated that platelet-rich plasma (PRP) and/or stem cells therapy could play an important role in the treatment of neuropathic pain, examining the hypothesis that applying this cell-based therapy to the site at which the pain originates can trigger the complete cascade of events involved in tissue repair, leading thereby to the permanent elimination of peripheral neuropathic pain (9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Based on the knowledge that NP is associated with neuroinflammation and ectopic activity as previously pointed out, and understanding that PRP possesses remarkable anti-inflammatory properties and has the ability of promoting axonal tissue repair and regeneration, thus stopping the spontaneous electrical activity and ceasing hyperexcitability (thereby eliminating neuropathic pain), we have conducted a clinical study in which PRP was used as a therapeutic option for the treatment of peripheral NP.…”

Section: Introductionmentioning

confidence: 99%

Platelet-rich plasma in treating peripheral neuropathic pain. Preliminary report

Lopez¹,

Cortes²,

García-Ceballos³

et al. 2017

Rev. Soc. Esp. Dolor.

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“…Intrathecal administration is a common drug-given approachof pain research. The intrathecal administration of stem cells allows the target for DRGs and spinal cord in the pain pathway and helps to clarify the underlying mechanisms (14). Recently, intranasal delivery is emerging as a noninvasive option for delivering stem cells with minimal peripheral exposure (15).…”

Section: Multiple Approaches For Stem Cells Delivery In the Treatmentmentioning

confidence: 99%

Stem Cells for the Treatment of Neuropathic Pain

Xie¹,

Yue²,

Guan³

et al. 2017

J Anesth Perioper Med

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Aim of review:Neuropathic pain induced by injury to the somatosensory system is a great clinical problem. Despite multiple therapeutic strategies, the medical community still faces a challenge to treat neuropathic pain in a complete and definitive way, since the pathogenesis of this hypersensitive state is very complex. Stem cell transplantation may be an important approach for the treatment of neuropathic pain. This article aimed to review important and illustrative results from recent stem cell studies under various neuropathic pain conditions and to interpret their clinical implications for stem cell transplantation. Methods: We reviewed recent articles and literatures about stem cells for the treatment of neuropathic pain, in order to identify the types of stem cells, delivery approaches and the advances of stem cells for the treatment of peripheral nerve injury induced neuropathic pain, painful diabetic peripheral neuropathy and spinal cord injury (SCI) induced chronic pain. Recent findings: Recently, the successful use of stem cell for the treatment of a diverse spectrum of diseases in animals has attracted more attentions from pain scientists. Accumulating evidence has shown that stem cell transplantation has a therapeutic effect on neuropathic pain. Stem cell transplantation can effectively relieve neuropathic pain under different pathological conditions. However, it is interesting to point out that peripheral neuropathic pain seems to be more responsive to stem cell therapy than SCI-induced chronic pain. Moreover, stem cell treatment does not always exert positive results in SCI-induced chronic pain (e.g. aggravating pain above the lesion spinal cord segment). Conclusion:The analgesic effect of stem cells depends on the capacity to offer a multipotent cellular source for replacing injured neural cells and delivering trophic factors to lesion sites. Stem cell researches should focus on both experimental and clinical studies of

show abstract

Intrathecal bone marrow stromal cells inhibit neuropathic pain via TGF-β secretion

Cited by 186 publications

References 58 publications

A Promising New Approach for the Treatment of Inflammatory Pain: Transfer of Stem Cell-Derived Tyrosine Hydroxylase-Positive Cells

A Promising New Approach for the Treatment of Inflammatory Pain: Transfer of Stem Cell-Derived Tyrosine Hydroxylase-Positive Cells

Platelet-rich plasma in treating peripheral neuropathic pain. Preliminary report

Stem Cells for the Treatment of Neuropathic Pain

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