Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease of cortical, brainstem, and spinal motor neurons (MNs) that leads to skeletal muscle weakness and atrophy, with death typically resulting from respiratory failure 2 to 4 years after disease diagnosis. Changes in executive function are common and occur in up to 50% of individuals, and up to 15% of persons with ALS manifest frontotemporal dementia due to neuronal dysfunction in the prefrontal and temporal cortex .. The disease exhibits clinical and pathophysiologic heterogeneity; both familial and sporadic cases occur, and the underlying genetic cause also varies, although mutations to C9ORF72, SOD1, TARDBP, and FUS are the most common.
There is no cure for ALS; the Food and Drug Administration (FDA) has approved riluzole [6], a putative glutamate receptor antagonist, and edaravone [7], a possible free radical scavenger, which produce modest benefits. The heterogeneity of ALS, both from a molecular standpoint and clinical phenotype, suggests that a pharmacological one-solution-fits-all approach may be challenging, which has been borne out by the lack of successful trials to date.
Stem cells were originally proposed as an ALS treatment to replenish the populations of progressively lost MNs. Stem cells possess the ability to self-renew and maintain an undifferentiated state. When they divide, the parent cell retains stemness while the daughter cell can differentiate. In order to integrate seamlessly with preexisting neural circuits, transplanted stem cell-derived MNs need to project axons, frequently over significant distances, and synapse with endogenous neurons and muscle, all the while enduring a diseased microenviroment. UC-MSCs have emerged as a promising avenue for treating amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disorder. These cells, derived from the umbilical cord’s Wharton’s jelly, exhibit anti-inflammatory, neuroprotective, and regenerative properties, making them a focal point of ALS research. Several preclinical studies indicated that stem cell therapy for ALS could work if the correct conditions, i.e., stem cell source, dose, and delivery methods, could be achieved in humans.
UC-MSCs exert their therapeutic effects through several mechanisms:
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.
View the Study: https://pmc.ncbi.nlm.nih.gov/articles/PMC6431432/
Motor neurons (MN) degeneration is a main feature of amyotrophic lateral sclerosis (ALS), a neurological disorder with a progressive course. The diagnosis of ALS is essentially a clinical one. Most common symptoms include a gradual neurological deterioration that reflect the impairment and subsequent loss of muscle functions. Up-to-date ALS has no therapy that would prevent or cure a disease. Modern therapeutic strategies comprise of neuroprotective treatment focused on antiglutamatergic, antioxidant, antiapoptotic, and anti-inflammatory molecules. Stem cells application and gene therapy has provided researchers with a powerful tool for discovery of new mechanisms and therapeutic agents, as well as opened new perspectives for patients and family members. Here, we review latest progress made in basic, translational and clinical stem cell research related to the ALS. We overviewed results of preclinical and clinical studies employing cell-based therapy to treat neurodegenerative disorders. A special focus has been made on the neuroprotective properties of adult mesenchymal stromal cells (MSC) application into ALS patients. Finally, we overviewed latest progress in the field of embryonic and induced pluripotent stem cells used for the modeling and application during neurodegeneration in general and in ALS in particular.
View the Study: https://pmc.ncbi.nlm.nih.gov/articles/PMC5660803/
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle paralysis determined by the degeneration of motoneurons in the motor cortex brainstem and spinal cord. The ALS pathogenetic mechanisms are still unclear, despite the wealth of studies demonstrating the involvement of several altered signaling pathways, such as mitochondrial dysfunction, glutamate excitotoxicity, oxidative stress and neuroinflammation. To date, the proposed therapeutic strategies are targeted to one or a few of these alterations, resulting in only a minimal effect on disease course and survival of ALS patients. The involvement of different mechanisms in ALS pathogenesis underlines the need for a therapeutic approach targeted to multiple aspects. Mesenchymal stem cells (MSC) can support motoneurons and surrounding cells, reduce inflammation, stimulate tissue regeneration and release growth factors. On this basis, MSC have been proposed as promising candidates to treat ALS. However, due to the drawbacks of cell therapy, the possible therapeutic use of extracellular vesicles (EVs) released by stem cells is raising increasing interest. The present review summarizes the main pathological mechanisms involved in ALS and the related therapeutic approaches proposed to date, focusing on MSC therapy and their preclinical and clinical applications. Moreover, the nature and characteristics of EVs and their role in recapitulating the effect of stem cells are discussed, elucidating how and why these vesicles could provide novel opportunities for ALS treatment.
View the Study: https://pmc.ncbi.nlm.nih.gov/articles/PMC5359305/
Mesenchymal stem cells (MSCs) have been extensively investigated for the treatment of various diseases. The therapeutic potential of MSCs is attributed to complex cellular and molecular mechanisms of action including differentiation into multiple cell lineages and regulation of immune responses via immunomodulation. The plasticity of MSCs in immunomodulation allow these cells to exert different immune effects depending on different diseases. Understanding the biology of MSCs and their role in treatment is critical to determine their potential for various therapeutic applications and for the development of MSC-based regenerative medicine. This review summarizes the recent progress of particular mechanisms underlying the tissue regenerative properties and immunomodulatory effects of MSCs. We focused on discussing the functional roles of paracrine activities, direct cell–cell contact, mitochondrial transfer, and extracellular vesicles related to MSC-mediated effects on immune cell responses, cell survival, and regeneration. This will provide an overview of the current research on the rapid development of MSC-based therapies.
View the Study: https://pmc.ncbi.nlm.nih.gov/articles/PMC7223321/
Mesenchymal stromal cells are multipotent cells that are being used to treat a variety of medical conditions. Over the past decade, there has been considerable excitement about using MSCs to treat neurodegenerative diseases, which are diseases that are typically fatal and without other robust therapies. In this review, we discuss the proposed MSC mechanisms of action in neurodegenerative diseases, which include growth factor secretion, exosome secretion, and attenuation of neuroinflammation. We then provide a summary of preclinical and early clinical work on MSC therapies in amyotrophic lateral sclerosis, multiple system atrophy, Parkinson’s disease, and Alzheimer’s disease. Continued rigorous and controlled studies of MSC therapies will be critical in order to establish efficacy and protect patients from possible untoward side effects.
View the Study: https://pmc.ncbi.nlm.nih.gov/articles/PMC6643282/
