scholarly journals Repeated infusion of mesenchymal stem cells maintain the condition to inhibit deteriorated motor function, leading to an extended lifespan in the SOD1G93A rat model of amyotrophic lateral sclerosis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hirotoshi Magota ◽  
Masanori Sasaki ◽  
Yuko Kataoka-Sasaki ◽  
Shinichi Oka ◽  
Ryo Ukai ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Amyotrophic Lateral Sclerosis ◽  
Mesenchymal Stem Cells ◽  
Motor Function ◽  
Motor Neurons ◽  
Rat Model ◽  
Repeated Administration ◽  
Single Infusion ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative fatal disorder in which motor neurons within the brain and spinal cord degenerate. A single infusion of mesenchymal stem cells (MSCs) delays disease progression by protecting motor neurons and restoring the blood-spinal cord barrier in the SOD1G93A transgenic ALS rat model. However, the therapeutic effect of a single infusion of MSCs is transient and does not block disease progression. In this study, we demonstrated that repeated administration of MSCs (weekly, four times) increased the survival period, protected motor functions, and reduced deterioration of locomotor activity compared to a single infusion and vehicle infusion, after which rats displayed progressive deterioration of hind limb function. We also compared the days until gait ability was lost in rats and found that the repeated-infused group maintained gait ability compared to the single-infusion and vehicle-infusion groups. These results suggest that repeated administration of MSCs may prevent the deterioration of motor function and extend the lifespan in ALS.

Intravenous infusion of mesenchymal stem cells delays disease progression in the SOD1G93A transgenic amyotrophic lateral sclerosis rat model

2021 ◽  
Vol 1757 ◽  
pp. 147296
Author(s):  
Hirotoshi Magota ◽  
Masanori Sasaki ◽  
Yuko Kataoka-Sasaki ◽  
Shinichi Oka ◽  
Ryo Ukai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Amyotrophic Lateral Sclerosis ◽  
Mesenchymal Stem Cells ◽  
Disease Progression ◽  
Rat Model ◽  
Intravenous Infusion ◽  
Lateral Sclerosis

scholarly journals Intravenous Mesenchymal Stem Cells Improve Survival and Motor Function in Experimental Amyotrophic Lateral Sclerosis

2012 ◽  
Vol 18 (5) ◽  
pp. 794-804 ◽  
Author(s):  
Antonio Uccelli ◽  
Marco Milanese ◽  
Maria Cristina Principato ◽  
Sara Morando ◽  
Tiziana Bonifacino ◽  
...  
Keyword(s):  
Stem Cells ◽  
Amyotrophic Lateral Sclerosis ◽  
Mesenchymal Stem Cells ◽  
Motor Function ◽  
Lateral Sclerosis

scholarly journals Mesenchymal Stem Cells in Treatment of Spinal Cord Injury and Amyotrophic Lateral Sclerosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Eva Sykova ◽  
Dasa Cizkova ◽  
Sarka Kubinova
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Amyotrophic Lateral Sclerosis ◽  
Mesenchymal Stem Cells ◽  
Clinical Studies ◽  
Differentiation Potential ◽  
Positive Effects ◽  
Cord Injury ◽  
Lateral Sclerosis

Preclinical and clinical studies with various stem cells, their secretomes, and extracellular vesicles (EVs) indicate their use as a promising strategy for the treatment of various diseases and tissue defects, including neurodegenerative diseases such as spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS). Autologous and allogenic mesenchymal stem cells (MSCs) are so far the best candidates for use in regenerative medicine. Here we review the effects of the implantation of MSCs (progenitors of mesodermal origin) in animal models of SCI and ALS and in clinical studies. MSCs possess multilineage differentiation potential and are easily expandable in vitro. These cells, obtained from bone marrow (BM), adipose tissue, Wharton jelly, or even other tissues, have immunomodulatory and paracrine potential, releasing a number of cytokines and factors which inhibit the proliferation of T cells, B cells, and natural killer cells and modify dendritic cell activity. They are hypoimmunogenic, migrate toward lesion sites, induce better regeneration, preserve perineuronal nets, and stimulate neural plasticity. There is a wide use of MSC systemic application or MSCs seeded on scaffolds and tissue bridges made from various synthetic and natural biomaterials, including human decellularized extracellular matrix (ECM) or nanofibers. The positive effects of MSC implantation have been recorded in animals with SCI lesions and ALS. Moreover, promising effects of autologous as well as allogenic MSCs for the treatment of SCI and ALS were demonstrated in recent clinical studies.

scholarly journals CRISPR/Cas9-Mediated Gene Correction to Understand ALS

2020 ◽  
Vol 21 (11) ◽  
pp. 3801
Author(s):  
Yeomin Yun ◽  
Yoon Ha
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Pluripotent Stem Cells ◽  
Gene Correction ◽  
Genetic Origin ◽  
Sporadic Cases ◽  
Induced Pluripotent ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the death of motor neurons in the spinal cord and brainstem. ALS has a diverse genetic origin; at least 20 genes have been shown to be related to ALS. Most familial and sporadic cases of ALS are caused by variants of the SOD1, C9orf72, FUS, and TARDBP genes. Genome editing using clustered regularly interspaced short palindromic repeats/CRISPR-associated system 9 (CRISPR/Cas9) can provide insights into the underlying genetics and pathophysiology of ALS. By correcting common mutations associated with ALS in animal models and patient-derived induced pluripotent stem cells (iPSCs), CRISPR/Cas9 has been used to verify the effects of ALS-associated mutations and observe phenotype differences between patient-derived and gene-corrected iPSCs. This technology has also been used to create mutations to investigate the pathophysiology of ALS. Here, we review recent studies that have used CRISPR/Cas9 to understand the genetic underpinnings of ALS.

scholarly journals Mesenchymal Stem Cells: A Potential Therapeutic Approach for Amyotrophic Lateral Sclerosis?

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Agnese Gugliandolo ◽  
Placido Bramanti ◽  
Emanuela Mazzon
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Amyotrophic Lateral Sclerosis ◽  
Mesenchymal Stem Cells ◽  
Motor Neurons ◽  
Experimental Models ◽  
Partial Recovery ◽  
Rodent Models ◽  
Beneficial Effects ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of both upper and lower motor neurons. Patients show both motor and extra-motor symptoms. A cure is not available at this time, and the disease leads to death within 3–5 years, mainly due to respiratory failure. Stem cell therapy is arising as a new promising approach for the treatment of neurodegenerative disorders. In particular, mesenchymal stem cells (MSCs) seem the most suitable type of stem cells, thanks to their demonstrated beneficial effects in different experimental models, to the easy availability, and to the lack of ethical problems. In this review, we focused on the studies involving ALS rodent models and clinical trials in order to understand the potential beneficial effects of MSC transplantation. In different ALS rodent models, the administration of MSCs induced a delay in disease progression and at least a partial recovery of the motor function. In addition, clinical trials evidenced the feasibility and safety of MSC transplantation in ALS patients, given that no major adverse events were recorded. However, only partial improvements were shown. For this reason, more studies and trials are needed to clarify the real effectiveness of MSC-based therapy in ALS.

Riluzole Exhibits No Therapeutic Efficacy on a Transgenic Rat model of Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 17 (3) ◽  
pp. 275-285 ◽  
Author(s):  
Si Chen ◽  
Qiao Liao ◽  
Ke Lu ◽  
Jinxia Zhou ◽  
Cao Huang ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Rat Model ◽  
Microglial Activation ◽  
Transgenic Rat ◽  
Intragastric Administration ◽  
Behavioral Deficits ◽  
Als Patients ◽  
Lateral Sclerosis ◽  
Transgenic Rat Model

Background: Amyotrophic lateral sclerosis (ALS) is a neurological disorder clinically characterized by motor system dysfunction, with intraneuronal accumulation of the TAR DNAbinding protein 43 (TDP-43) being a pathological hallmark. Riluzole is a primarily prescribed medicine for ALS patients, while its therapeutical efficacy appears limited. TDP-43 transgenic mice are existing animal models for mechanistic/translational research into ALS. Methods: We developed a transgenic rat model of ALS expressing a mutant human TDP-43 transgene (TDP-43M337V) and evaluated the therapeutic effect of Riluzole on this model. Relative to control, rats with TDP-43M337V expression promoted by the neurofilament heavy subunit (NEF) gene or specifically in motor neurons promoted by the choline acetyltransferase (ChAT) gene showed progressive worsening of mobility and grip strength, along with loss of motor neurons, microglial activation, and intraneuronal accumulation of TDP-43 and ubiquitin aggregations in the spinal cord. Results: Compared to vehicle control, intragastric administration of Riluzole (30 mg/kg/d) did not mitigate the behavioral deficits nor alter the neuropathologies in the transgenics. Conclusion: These findings indicate that transgenic rats recapitulate the basic neurological and neuropathological characteristics of human ALS, while Riluzole treatment can not halt the development of the behavioral and histopathological phenotypes in this new transgenic rodent model of ALS.

Bone marrow mesenchymal stem cells-derived exosomes reduce apoptosis and inflammatory response during spinal cord injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway

2021 ◽  
pp. 096032712110033
Author(s):  
Liying Fan ◽  
Jun Dong ◽  
Xijing He ◽  
Chun Zhang ◽  
Ting Zhang
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Motor Function ◽  
Inflammatory Factors ◽  
Cord Injury ◽  
Marrow Mesenchymal Stem Cells ◽  
Apoptosis And Inflammation

Spinal cord injury (SCI) is one of the most common destructive injuries, which may lead to permanent neurological dysfunction. Currently, transplantation of bone marrow mesenchymal stem cells (BMSCs) in experimental models of SCI shows promise as effective therapies. BMSCs secrete various factors that can regulate the microenvironment, which is called paracrine effect. Among these paracrine substances, exosomes are considered to be the most valuable therapeutic factors. Our study found that BMSCs-derived exosomes therapy attenuated cell apoptosis and inflammation response in the injured spinal cord tissues. In in vitro studies, BMSCs-derived exosomes significantly inhibited lipopolysaccharide (LPS)-induced PC12 cell apoptosis, reduced the secretion of pro-inflammatory factors including tumor necrosis factor (TNF)-α and IL (interleukin)-1β and promoted the secretion of anti-inflammatory factors including IL-10 and IL-4. Moreover, we found that LPS-induced protein expression of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear transcription factor-κB (NF-κB) was significantly downregulated after treatment with BMSCs-derived exosomes. In in vivo studies, we found that hindlimb motor function was significantly improved in SCI rats with systemic administration of BMSCs-derived exosomes. We also observed that the expression of pro-apoptotic proteins and pro-inflammatory factors was significantly decreased, while the expression of anti-apoptotic proteins and anti-inflammatory factors were upregulated in SCI rats after exosome treatment. In conclusion, BMSCs-derived exosomes can inhibit apoptosis and inflammation response induced by injury and promote motor function recovery by inhibiting the TLR4/MyD88/NF-κB signaling pathway, which suggests that BMSCs-derived exosomes are expected to become a new therapeutic strategy for SCI.

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