-
International Journal of Molecular... Jul 2023Recovery from a traumatic spinal cord injury (TSCI) is challenging due to the limited regenerative capacity of the central nervous system to restore cells, myelin, and... (Review)
Review
Recovery from a traumatic spinal cord injury (TSCI) is challenging due to the limited regenerative capacity of the central nervous system to restore cells, myelin, and neural connections. Cell therapy, particularly with mesenchymal stem cells (MSCs), holds significant promise for TSCI treatment. This systematic review aims to analyze the efficacy, safety, and therapeutic potential of MSC-based cell therapies in TSCI. A comprehensive search of PUBMED and COCHRANE databases until February 2023 was conducted, combining terms such as "spinal cord injury," "stem cells," "stem cell therapy," "mesenchymal stem cells," and "traumatic spinal cord injury". Among the 53 studies initially identified, 22 (21 clinical trials and 1 case series) were included. Findings from these studies consistently demonstrate improvements in AIS (ASIA Impairment Scale) grades, sensory scores, and, to a lesser extent, motor scores. Meta-analyses further support these positive outcomes. MSC-based therapies have shown short- and medium-term safety, as indicated by the absence of significant adverse events within the studied timeframe. However, caution is required when drawing generalized recommendations due to the limited scientific evidence available. Further research is needed to elucidate the long-term safety and clinical implications of these advancements. Although significant progress has been made, particularly with MSC-based therapies, additional studies exploring other potential future therapies such as gene therapies, neurostimulation techniques, and tissue engineering approaches are essential for a comprehensive understanding of the evolving TSCI treatment landscape.
Topics: Humans; Mesenchymal Stem Cell Transplantation; Spinal Cord Injuries; Cell- and Tissue-Based Therapy; Myelin Sheath; Mesenchymal Stem Cells; Spinal Cord
PubMed: 37511478
DOI: 10.3390/ijms241411719 -
Human Cell Jan 2024Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system (CNS), characterized by demyelination and... (Review)
Review
Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system (CNS), characterized by demyelination and axonal loss. It is induced by attack of autoreactive lymphocytes on the myelin sheath and endogenous remyelination failure, eventually leading to accumulation of neurological disability. Disease-modifying agents can successfully address inflammatory relapses, but have low efficacy in progressive forms of MS, and cannot stop the progressive neurodegenerative process. Thus, the stem cell replacement therapy approach, which aims to overcome CNS cell loss and remyelination failure, is considered a promising alternative treatment. Although the mechanisms behind the beneficial effects of stem cell transplantation are not yet fully understood, neurotrophic support, immunomodulation, and cell replacement appear to play an important role, leading to a multifaceted fight against the pathology of the disease. The present systematic review is focusing on the efficacy of stem cells to migrate at the lesion sites of the CNS and develop functional oligodendrocytes remyelinating axons. While most studies confirm the improvement of neurological deficits after the administration of different stem cell types, many critical issues need to be clarified before they can be efficiently introduced into clinical practice.
Topics: Humans; Multiple Sclerosis; Neurodegenerative Diseases; Myelin Sheath; Stem Cells; Oligodendroglia
PubMed: 37985645
DOI: 10.1007/s13577-023-01006-1 -
Frontiers in Cellular Neuroscience 2022To compare the safety and effectiveness of transplanted cells from different sources for spinal cord injury (SCI).
OBJECTIVE
To compare the safety and effectiveness of transplanted cells from different sources for spinal cord injury (SCI).
DESIGN
A systematic review and Bayesian network meta-analysis.
DATA SOURCES
Medline, Embase, and the Cochrane Central Register of Controlled Trials.
STUDY SELECTION
We included randomized controlled trials, case-control studies, and case series related to cell transplantation for SCI patients, that included at least 1 of the following outcome measures: American Spinal Cord Injury Association (ASIA) Impairment Scale (AIS grade), ASIA motor score, ASIA sensory score, the Functional Independence Measure score (FIM), International Association of Neurorestoratology Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS), or adverse events. Follow-up data were analyzed at 6 and 12 months.
RESULTS
Forty-four eligible trials, involving 1,266 patients, investigated 6 treatments: olfactory ensheathing cells (OECs), neural stem cells/ neural progenitor cells (NSCs), mesenchymal stem cells (MSCs), Schwann cells, macrophages, and combinations of cells (MSCs plus Schwann cells). Macrophages improved the AIS grade at 12 months (mean 0.42, 95% credible interval: 0-0.91, low certainty) and FIM score at 12 months (42.83, 36.33-49.18, very low certainty). MSCs improved the AIS grade at 6 months (0.42, 0.15-0.73, moderate certainty), the motor score at 6 months (4.43, 0.91-7.78, moderate certainty), light touch at 6 (10.01, 5.81-13.88, moderate certainty) and 12 months (11.48, 6.31-16.64, moderate certainty), pinprick score at 6 (14.54, 9.76-19.46, moderate certainty) and 12 months (12.48, 7.09-18.12, moderate certainty), and the IANR-SCIFRS at 6 (3.96, 0.62-6.97, moderate certainty) and 12 months (5.54, 2.45-8.42, moderate certainty). OECs improved the FIM score at 6 months (9.35, 1.71-17.00, moderate certainty). No intervention improved the motor score significantly at 12 months. The certainty of other interventions was low or very low. Overall, the number of adverse events associated with transplanted cells was low.
CONCLUSIONS
Patients with SCI who receive transplantation of macrophages, MSCs, NSCs, or OECs may have improved disease prognosis. MSCs are the primary recommendations. Further exploration of the mechanism of cell transplantation in the treatment of SCI, transplantation time window, transplantation methods, and monitoring of the number of transplanted cells and cell survival is needed.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier: CRD 42021282043.
PubMed: 35444516
DOI: 10.3389/fncel.2022.860131 -
IBRO Neuroscience Reports Dec 2023, the pathogen that causes human leprosy, has a unique affinity for infecting and persisting inside Schwann cells, the principal glia of the peripheral nervous system.... (Review)
Review
, the pathogen that causes human leprosy, has a unique affinity for infecting and persisting inside Schwann cells, the principal glia of the peripheral nervous system. Several studies have focused on this intricate host-pathogen interaction as an attempt to advance the current knowledge of the mechanisms governing nerve destruction and disease progression. However, during the chronic course of leprosy neuropathy, Schwann cells can respond to and internalize both live and dead and bacilli-derived antigens, and this may result in divergent cellular pathobiological responses. This may also distinctly contribute to tissue degeneration, failure to repair, inflammatory reactions, and nerve fibrosis, hallmarks of the disease. Therefore, the present study systematically searched for published studies on -Schwann cell interaction to summarize the findings and provide a focused discussion of Schwann cell dynamics following challenge with leprosy bacilli.
PubMed: 38204570
DOI: 10.1016/j.ibneur.2023.05.009 -
International Journal of Molecular... Mar 2022A growing body of studies indicate that small noncoding RNAs, especially microRNAs (miRNA), play a crucial role in response to peripheral nerve injuries. During...
A growing body of studies indicate that small noncoding RNAs, especially microRNAs (miRNA), play a crucial role in response to peripheral nerve injuries. During Wallerian degeneration and regeneration processes, they orchestrate several pathways, in particular the MAPK, AKT, and EGR2 (KROX20) pathways. Certain miRNAs show specific expression profiles upon a nerve lesion correlating with the subsequent nerve regeneration stages such as dedifferentiation and with migration of Schwann cells, uptake of debris, neurite outgrowth and finally remyelination of regenerated axons. This review highlights (a) the specific expression profiles of miRNAs upon a nerve lesion and (b) how miRNAs regulate nerve regeneration by acting on distinct pathways and linked proteins. Shedding light on the role of miRNAs associated with peripheral nerve regeneration will help researchers to better understand the molecular mechanisms and deliver targets for precision medicine.
Topics: Humans; MicroRNAs; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Schwann Cells; Sciatic Nerve
PubMed: 35408800
DOI: 10.3390/ijms23073440 -
International Journal of Molecular... Jan 2021Traumatic peripheral nerve lesions affect hundreds of thousands of patients every year; their consequences are life-altering and often devastating and cause alterations... (Meta-Analysis)
Meta-Analysis
Traumatic peripheral nerve lesions affect hundreds of thousands of patients every year; their consequences are life-altering and often devastating and cause alterations in movement and sensitivity. Spontaneous peripheral nerve recovery is often inadequate. In this context, nowadays, cell therapy represents one of the most innovative approaches in the field of nerve repair therapies. The purpose of this systematic review is to discuss the features of different types of mesenchymal stem cells (MSCs) relevant for peripheral nerve regeneration after nerve injury. The published literature was reviewed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A combination of the keywords "nerve regeneration", "stem cells", "peripheral nerve injury", "rat", and "human" were used. Additionally, a "MeSH" research was performed in PubMed using the terms "stem cells" and "nerve regeneration". The characteristics of the most widely used MSCs, their paracrine potential, targeted stimulation, and differentiation potentials into Schwann-like and neuronal-like cells are described in this paper. Considering their ability to support and stimulate axonal growth, their remarkable paracrine activity, their presumed differentiation potential, their extremely low immunogenicity, and their high survival rate after transplantation, ADSCs appear to be the most suitable and promising MSCs for the recovery of peripheral nerve lesion. Clinical considerations are finally reported.
Topics: Animals; Cell Differentiation; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Nerve Regeneration; Peripheral Nerves; Rats; Schwann Cells; Sciatic Nerve
PubMed: 33430035
DOI: 10.3390/ijms22020572 -
Journal of Neurotrauma Aug 2011Cell transplantation therapies have become a major focus in pre-clinical research as a promising strategy for the treatment of spinal cord injury (SCI). In this article,... (Review)
Review
Cell transplantation therapies have become a major focus in pre-clinical research as a promising strategy for the treatment of spinal cord injury (SCI). In this article, we systematically review the available pre-clinical literature on the most commonly used cell types in order to assess the body of evidence that may support their translation to human SCI patients. These cell types include Schwann cells, olfactory ensheathing glial cells, embryonic and adult neural stem/progenitor cells, fate-restricted neural/glial precursor cells, and bone-marrow stromal cells. Studies were included for review only if they described the transplantation of the cell substrate into an in-vivo model of traumatic SCI, induced either bluntly or sharply. Using these inclusion criteria, 162 studies were identified and reviewed in detail, emphasizing their behavioral effects (although not limiting the scope of the discussion to behavioral effects alone). Significant differences between cells of the same "type" exist based on the species and age of donor, as well as culture conditions and mode of delivery. Many of these studies used cell transplantations in combination with other strategies. The systematic review makes it very apparent that cells derived from rodent sources have been the most extensively studied, while only 19 studies reported the transplantation of human cells, nine of which utilized bone-marrow stromal cells. Similarly, the vast majority of studies have been conducted in rodent models of injury, and few studies have investigated cell transplantation in larger mammals or primates. With respect to the timing of intervention, nearly all of the studies reviewed were conducted with transplantations occurring subacutely and acutely, while chronic treatments were rare and often failed to yield functional benefits.
Topics: Animals; Bone Marrow Transplantation; Disease Models, Animal; Humans; Neuroglia; Neurons; Spinal Cord Injuries; Stem Cell Transplantation
PubMed: 20146557
DOI: 10.1089/neu.2009.1177 -
Journal of Clinical Laboratory Analysis Aug 2022Non-coding RNAs (ncRNAs) are involved in neuropathic pain development. Herein, we systematically searched for neuropathic pain-related ncRNAs expression changes,... (Review)
Review
BACKGROUND
Non-coding RNAs (ncRNAs) are involved in neuropathic pain development. Herein, we systematically searched for neuropathic pain-related ncRNAs expression changes, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular non-coding RNAs (circRNAs).
METHODS
We searched two databases, PubMed and GeenMedical, for relevant studies.
RESULTS
Peripheral nerve injury or noxious stimuli can induce extensive changes in the expression of ncRNAs. For example, higher serum miR-132-3p, -146b-5p, and -384 was observed in neuropathic pain patients. Either sciatic nerve ligation, dorsal root ganglion (DRG) transaction, or ventral root transection (VRT) could upregulate miR-21 and miR-31 while downregulating miR-668 and miR-672 in the injured DRG. lncRNAs, such as early growth response 2-antisense-RNA (Egr2-AS-RNA) and Kcna2-AS-RNA, were upregulated in Schwann cells and inflicted DRG after nerve injury, respectively. Dysregulated circRNA homeodomain-interacting protein kinase 3 (circHIPK3) in serum and the DRG, abnormally expressed lncRNAs X-inactive specific transcript (XIST), nuclear enriched abundant transcript 1 (NEAT1), small nucleolar RNA host gene 1 (SNHG1), as well as ciRS-7, zinc finger protein 609 (cirZNF609), circ_0005075, and circAnks1a in the spinal cord were suggested to participate in neuropathic pain development. Dysregulated miRNAs contribute to neuropathic pain via neuroinflammation, autophagy, abnormal ion channel expression, regulating pain-related mediators, protein kinases, structural proteins, neurotransmission excitatory-inhibitory imbalances, or exosome miRNA-mediated neuron-glia communication. In addition, lncRNAs and circRNAs are essential in neuropathic pain by acting as antisense RNA and miRNA sponges, epigenetically regulating pain-related molecules expression, or modulating miRNA processing.
CONCLUSIONS
Numerous dysregulated ncRNAs have been suggested to participate in neuropathic pain development. However, there is much work to be done before ncRNA-based analgesics can be clinically used for various reasons such as conservation among species, proper delivery, stability, and off-target effects.
Topics: Ganglia, Spinal; Humans; MicroRNAs; Neuralgia; RNA, Circular; RNA, Long Noncoding
PubMed: 35808924
DOI: 10.1002/jcla.24592 -
Frontiers in Molecular Neuroscience 2023The pathomechanisms underlying migraine are intricate and remain largely unclear. Initially regarded as a neuronal disorder, migraine research primarily concentrated on...
BACKGROUND
The pathomechanisms underlying migraine are intricate and remain largely unclear. Initially regarded as a neuronal disorder, migraine research primarily concentrated on understanding the pathophysiological changes within neurons. However, recent advances have revealed the significant involvement of neuroinflammation and the neuro-glio-vascular interplay in migraine pathogenesis.
METHODS
A systematic search was conducted in PubMed, Scopus, and Web of Science databases from their inception until November 2022. The retrieved results underwent a screening process based on title and abstract, and the full texts of the remaining papers were thoroughly assessed for eligibility. Only studies that met the predetermined inclusion criteria were included in the review.
RESULTS
Fifty-nine studies, consisting of 6 human studies and 53 animal studies, met the inclusion criteria. Among the 6 human studies, 2 focused on genetic analyses, while the remaining studies employed functional imaging, serum analyses and clinical trials. Regarding the 53 animal studies investigating glial cells in migraine, 19 of them explored the role of satellite glial cells and/or Schwann cells in the trigeminal ganglion and/or trigeminal nerve. Additionally, 17 studies highlighted the significance of microglia and/or astrocytes in the trigeminal nucleus caudalis, particularly in relation to central sensitization during migraine chronification. Furthermore, 17 studies examined the involvement of astrocytes and/or microglia in the cortex.
CONCLUSION
Glial cells, including astrocytes, microglia, satellite glial cells and Schwann cells in the central and peripheral nervous system, participate both in the development as well as chronic progression of migraine in disease-associated regions such as the trigeminovascular system, trigeminal nucleus caudalis and cortex, among other brain regions.
PubMed: 37456527
DOI: 10.3389/fnmol.2023.1219574 -
Cellular Physiology and Biochemistry :... 2015Schwann cells (SCs) which were demonstrated to be responsible for axonal myelination and ensheathing are widely studied and commonly used for cell transplantation to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIMS
Schwann cells (SCs) which were demonstrated to be responsible for axonal myelination and ensheathing are widely studied and commonly used for cell transplantation to treat spinal cord injury (SCI). We performed this meta-analysis to summarize the effects of SCs versus controls for locomotor recovery in rat models of traumatic SCI.
METHODS
Studies of the BBB scores after transplantation of SCs were searched out from Pubmed, Cochrane Library Medline databases and analyzed by Review Manager 5.2.5.
RESULTS
Thirteen randomized controlled animal trials were selected with 283 rats enrolled. The studies were divided to different subgroups by different models of SCI, different cell doses for transplantation, different sources of SCs and different transplantation ways. The pooled results of this meta-analysis suggested that SCs transplantation cannot significantly improve the locomotor recovery at a short time after intervention (1 week after transplantation) in both impacted and hemi-sected SCI models. However, at a longer time after intervention (3, 5-7 and over 8 weeks after transplantation), significant improvement of BBB score emerged in SCs groups compared with control groups. Subgroup analyses revealed that SCs transplantation can significantly promote locomotor recovery regardless of in high or low doses of cells, from different sources (isolated from sciatic nerves or differentiated from bone marrow stromal cells(BMSCs)) and with or without scaffolding.
CONCLUSION
SCs seem to demonstrate substantial beneficial effects on locomotor recovery in a widely-used animal models of SCI.
Topics: Animals; Cell Transplantation; Locomotion; Rats; Schwann Cells; Spinal Cord Injuries
PubMed: 26605538
DOI: 10.1159/000438574