GSE115565 Human iPSC-derived GABAergic Interneuron Transplants Attenuate Neuropathic Pain

Contributor : John ManionSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensNeuropathic pain causes severe suffering and most patients are resilient to current therapies. A core element of neuropathic pain is the loss of inhibitory tone in the spinal cord. Previous studies have shown that foetal GABAergic neuron precursors can provide relief from pain. However, the source of these precursor cells and their multipotent status make them unsuitable for therapeutic use. Here we extend these findings by showing, for the first time, that spinally transplanted, terminally differentiated hiPSC-derived GABAergic (iGABAergic) neurons provide significant, long-term and safe relief from neuropathic pain induced by peripheral nerve injury in mice. Furthermore, iGABAergic Neuron transplants survive long term in the injured spinal cord and show evidence of synaptic integration. Together, this provides the proof in principle for the first viable GABAergic transplants to treat human neuropathic pain patients.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research

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Neuropathic pain causes severe suffering, and most patients are resistant to current therapies. A core element of neuropathic pain is the loss of inhibitory tone in the spinal cord. Previous studies have shown that foetal GABAergic neuron precursors can provide relief from pain. However, the source of these precursor cells and their multipotent status make them unsuitable for therapeutic use. Here, we extend these findings by showing, for the first time, that spinally transplanted, terminally differentiated human induced pluripotent stem cell-derived GABAergic (iGABAergic) neurons provide significant, long-term, and safe r...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
Abstract Spinal cord injury (SCI) produces both locomotor deficits and sensory dysfunction that greatly reduce the overall quality of life. Mechanisms underlying chronic pain include increased neuro-inflammation and changes in spinal processing of sensory signals, with reduced inhibitory GABAergic signaling a likely key player. Our previous research demonstrated that spinal transplantation of GABAergic neural progenitor cells (NPCs) reduced neuropathic pain while intensive locomotor training (ILT) could reduce development of pain and partially reverse already established pain behaviors. Therefore, we evaluate the ...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research
In this study, we reviewed the current progress of the studies on the involvement of lncRNAs in SCI, with the aim of drawing attention towards their roles in this debilitating condition. PMID: 31737660 [PubMed - in process]
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
Abstract OBJECTIVES: The aim of this study was to determine the role of microencapsulated olfactory ensheathing cells (MC-OECs) transplantation in rats with sciatic nerve injury-induced neuropathic pain, and its relationship with P2X4 receptor expression in the L4-5 spinal cord segment. METHODS: Olfactory bulb tissues of healthy Sprague Dawley (SD) rats were collected to culture olfactory ensheathing cells (OECs) using differential attachment methods. Seventy-two healthy SD rats were randomly assigned to four groups: the sham, chronic constriction injury (CCI), OECs, and MC-OECs groups. Mechanical paw withdra...
Source: Brain Research - Category: Neurology Authors: Tags: Brain Res Source Type: research
Abstract Neuropathic pain after spinal cord injury (SCI) is a complex condition that responds poorly to usual treatments. Cell transplantation represents a promising therapy; nevertheless, the ideal cell type in terms of neurogenic potential and effectiveness against pain remains largely controversial. Here, we evaluated the ability of fetal neural stem cells (fNSC) to relieve chronic pain and, secondarily, their effects on motor recovery. Adult Wistar rats with traumatic SCI were treated, 10 days after injury, with intra-spinal injections of culture medium (sham) or fNSCs extracted from telencephalic vesicles (TV...
Source: Cell Research - Category: Cytology Authors: Tags: Neural Regen Res Source Type: research
This study also found that Proteus DNA, a genus with many uropathogenic species (Drzewiecka, 2016), was more prevalent in women with OAB compared to asymptomatic controls (Curtiss et al., 2017). IC A recent study by Abernethy et al. suggested that the microbiome may play a role in IC (Abernethy et al., 2017). In this study, 16S rRNA analysis determined the microbiome of catheterized urine from women (n = 40) with IC was not dominated by a single genus and was less likely to contain Lactobacillus compared to asymptomatic women. Abernethy et al. also showed that L. acidophilus was associated with less severe scores on the ...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
Conclusion and Future Aspects This review summarizes available NTF expression data, compiles existing evidence on the effects of glial NTF signaling in healthy conditions and in disease models (Figure 1), and highlights the importance of this topic for future studies. The relationship between NTFs and glia is crucial for both the developing and adult brain. While some of these factors, such as NT-3 and CNTF, have highly potent effects on gliogenesis, others like BDNF and GDNF, are important for glia-mediated synapse formation. Neurotrophic factors play significant roles during neurodegenerative disorders. In many cases, ...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Publication date: Available online 10 February 2019Source: Neuroscience LettersAuthor(s): Wenjun Zhang, Yuguo Liu, Yi Sun, Zengxu LiuABSTRACTObjectivesThe aim of this study was to determine the role of microencapsulated olfactory ensheathing cell (MC-OEC) transplantation in rats with sciatic nerve injury-induced pain, and its relationship with P2 × 7 receptor expression in the L4-5 spinal cord segment.MethodsOlfactory bulb tissues of healthy Sprague Dawley (SD) rats were collected to culture olfactory ensheathing cells using differential attachment methods. Forty-eight healthy SD rats were randomly assi...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
ConclusionCell transplantation appears to be a safe therapeutic strategy possessing substantial beneficial effects in the patients with SCI in clinic. Moreover, treating SCI with stem cell, the dosage of cells between 1 –5 × 107 and 10 –20 × 107, in intermediate or chronic phase, minimally invasive techniques, may bring more advantage to SCI patient.Graphical abstractThese slides can be retrieved under Electronic Supplementary Material.
Source: European Spine Journal - Category: Orthopaedics Source Type: research
In conclusion, HSC ageing is characterised by reduced self-renewal, myeloid and platelet HSC skewing, and expanded clonal haematopoiesis that is considered a preleukaemic state. The underlying molecular mechanisms seem to be related to increased oxidative stress due to ROS accumulation and DNA damage, which are influenced by both cell- and cell non-autonomous mechanisms such as prolonged exposure to infections, inflammageing, immunosenescence, and age-related changes in the HSC niche. Thus, HSC ageing seems to be multifactorial and we are only beginning to connect all the dots. The Price of Progress or the Waste...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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