Cytokines secreted by mesenchymal stem cells reduce demyelination in an animal model of Charcot-Marie-Tooth disease

Jeon, Hong Jun; Kim, Hye J.; Doo, Hyun Myung; Chang, Eun‐Chul; Kwak, Geon; Mo, Won Min; Jang, So Young; Lee, Myoung Woo; Choi, Byung‐Ok; Hong, Young Bin

doi:10.1016/j.bbrc.2022.01.098

Cited by 5 publications

(5 citation statements)

References 38 publications

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“…Although other pharmacological treatments have been suggested through the years, most of them are muscle atrophy (108). Here, we also demonstrate, for the first time to our knowledge, the responsiveness of NF-L (109, 110) and Gdf15 (80,81) plasma biomarkers in a CMT1A model. Responsiveness of these translatable biomarkers is highly encouraging for their utility in parallel clinical trials of miRNA therapies.…”

Section: Discussionsupporting

confidence: 54%

A translatable RNAi-driven gene therapy silences PMP22/Pmp22 genes and improves neuropathy in CMT1A mice

Stavrou

Kagiava

Choudury

et al. 2022

Journal of Clinical Investigation

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Section: Discussionsupporting

confidence: 54%

A translatable RNAi-driven gene therapy silences PMP22/Pmp22 genes and improves neuropathy in CMT1A mice

Stavrou

Kagiava

Choudury

et al. 2022

Journal of Clinical Investigation

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“…A recent study indicated GDF15 did not vary between genetic variants CMT1a and PMP22 for the disease (Palu et al, 2023). This is supportive of findings from mouse models of CMT that show GDF15 was elevated in serum (Jennings et al, 2022) and in schwannoma cell media when transfected with PMP22 (Jeon et al, 2022).…”

Section: Elevated Gdf15 Is Associated With Neurodegenerative Disease ...supporting

confidence: 87%

A Systematic Review of the Neuroprotective Role and Biomarker Potential of GDF15 in Neurodegeneration

Isik,

Thomson,

Cueto

et al. 2024

Preprint

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Neurodegeneration is characteristically multifaceted, with limited therapeutic options. One of the chief pathophysiological mechanisms driving these conditions is neuroinflammation, prompting increasing clinical interest in immunomodulatory agents. Growth differentiation factor 15 (GDF15; previously also called macrophage inhibitory cytokine-1 or MIC-1), an anti-inflammatory cytokine with established neurotrophic properties, has emerged as a promising therapeutic agent in recent decades. However, methodological challenges and the delayed identification of its specific receptor GFRAL have hindered research progress. This review systematically examines literature about GDF15 in neurodegenerative diseases and neurotrauma. The evidence collated in this review indicates that GDF15 expression is upregulated in response to neurodegenerative pathophysiology and increasing its levels in preclinical models typically improves outcomes. Key knowledge gaps are addressed for future investigations to foster a more comprehensive understanding of the neuroprotective effects elicited by GDF15.

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“…An improvement in remyelination after NRPC transplantation in a dose-dependent manner was confirmed by an increase in myelin thickness seen with a TEM, which was similar to that seen in the W/T mice. Compared with other studies [7][8][9][10][11][12][13], the present study clearly found a treatment effect on myelin sheath thickness and a correlation between the axon diameter and G-ratio. In addition, significant improvements in the NCV and CMAP were confirmed in the NRPC groups, which indicates that NRPCs promote axonal regrowth and remyelination.…”

Section: Discussioncontrasting

confidence: 77%

“…Despite many attempts to develop CMT treatments, there are few specific treatments for this disease other than genetic counseling, symptomatic treatment, physical therapy, and rehabilitation treatments [27]. However, many treatments for CMT patients have still been studied, and drug therapies, including ascorbic acid, progesterone antagonists and modulators, PXT3003, HDAC6 inhibitors, P2X7 receptor modulators, and cytokines, have been reported [1,[7][8][9]. Recently, gene therapies, including AAV-Neurotrophin-3, antisense oligonucleotides, siRNA, AAV9-shRNA, CRISPR/Cas9-sgRNA, and AAV9-miRNA, have also been studied [2,[10][11][12][13].…”

Section: Discussionmentioning

confidence: 99%

“…The properly regulated expression and folding of PMP22 are essential for the development and maintenance of normal myelin in Schwann cells, and when this condition occurs abnormally, the overproduction of PMP22 proteins results in CMT1A [6]. Previously, the only methods for treatment were physical rehabilitation, pain control, and walking assistance, but now more than 100 related genes have been discovered, and the development of drug therapies [1,[7][8][9] and gene therapies [2,[10][11][12][13] is actively underway.…”

Section: Introductionmentioning

confidence: 99%

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Preclinical Efficacy of Peripheral Nerve Regeneration by Schwann Cell-like Cells Differentiated from Human Tonsil-Derived Mesenchymal Stem Cells in C22 Mice

Nam,

Park,

Yum

et al. 2023

Biomedicines

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Charcot–Marie–Tooth disease (CMT) is a hereditary disease with heterogeneous phenotypes and genetic causes. CMT type 1A (CMT1A) is a type of disease affecting the peripheral nerves and is caused by the duplication of the peripheral myelin protein 22 (PMP22) gene. Human tonsil-derived mesenchymal stem cells (TMSCs) are useful for stem cell therapy in various diseases and can be differentiated into Schwann cell-like cells (TMSC-SCs). We investigated the potential of TMSC-SCs called neuronal regeneration-promoting cells (NRPCs) for peripheral nerve and muscle regeneration in C22 mice, a model for CMT1A. We transplanted NRPCs manufactured in a good manufacturing practice facility into the bilateral thigh muscles of C22 mice and performed behavior and nerve conduction tests and histological and ultrastructural analyses. Significantly, the motor function was much improved, the ratio of myelinated axons was increased, and the G-ratio was reduced by the transplantation of NRPCs. The sciatic nerve and gastrocnemius muscle regeneration of C22 mice following the transplantation of NRPCs downregulated PMP22 overexpression, which was observed in a dose-dependent manner. These results suggest that NRPCs are feasible for clinical research for the treatment of CMT1A patients. Research applying NRPCs to other peripheral nerve diseases is also needed.

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Cytokines secreted by mesenchymal stem cells reduce demyelination in an animal model of Charcot-Marie-Tooth disease

Cited by 5 publications

References 38 publications

A translatable RNAi-driven gene therapy silences PMP22/Pmp22 genes and improves neuropathy in CMT1A mice

A translatable RNAi-driven gene therapy silences PMP22/Pmp22 genes and improves neuropathy in CMT1A mice

A Systematic Review of the Neuroprotective Role and Biomarker Potential of GDF15 in Neurodegeneration

Preclinical Efficacy of Peripheral Nerve Regeneration by Schwann Cell-like Cells Differentiated from Human Tonsil-Derived Mesenchymal Stem Cells in C22 Mice

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