Parkinson disease (PD) is a neurological movement disorder resulting primarily from damage to and degeneration of the nigrostriatal dopaminergic pathway. The pathway consists of neural populations in the substantia nigra that project to the striatum of the brain where they release dopamine. Diagnosis of PD is based on the presence of impaired motor features such as asymmetric or unilateral resting tremor, bradykinesia, and rigidity. Nonmotor features including cognitive impairment, sleep disorders, and autonomic dysfunction are also present. No cure for PD has been discovered, and treatment strategies focus on symptomatic management through restoration of dopaminergic activity.
Mesenchymal stem cells (MSCs) show promise in Parkinson’s disease (PD) treatment due to their ability to secrete trophic factors, modulate the immune system, and promote neurogenesis. They achieve this through various mechanisms, including:
the release of growth factors, exosomes, and other paracrine factors that support damaged tissue, reduce inflammation, and potentially differentiate into dopamine-producing cells.
Parkinson’s disease (PD) is a neurological movement disorder resulting primarily from damage to and degeneration of the nigrostriatal dopaminergic pathway. The pathway consists of neural populations in the substantia nigra that project to the striatum of the brain where they release dopamine. Diagnosis of PD is based on the presence of impaired motor features such as asymmetric or unilateral resting tremor, bradykinesia, and rigidity. Nonmotor features including cognitive impairment, sleep disorders, and autonomic dysfunction are also present. No cure for PD has been discovered, and treatment strategies focus on symptomatic management through restoration of dopaminergic activity. However, proposed cell replacement therapies are promising because midbrain dopaminergic neurons have been shown to restore dopaminergic neurotransmission and functionally rescue the dopamine-depleted striatum. In this review, we summarize our current understanding of the molecular pathogenesis of neurodegeneration in PD and discuss the development of new therapeutic strategies that have led to the initiation of exploratory clinical trials. We focus on the applications of stem cells for the treatment of PD and discuss how stem cell research has contributed to an understanding of PD, predicted the efficacy of novel neuroprotective therapeutics, and highlighted what we believe to be the critical areas for future research.
Parkinson’s Disease (PD) is an intractable disease resulting in localized neurodegeneration of dopaminergic neurons of the substantia nigra pars compacta. Many current therapies of PD can only address the symptoms and not the underlying neurodegeneration of PD. To better understand the pathophysiological condition, researchers continue to seek models that mirror PD’s phenotypic manifestations as closely as possible. Recent advances in the field of cellular reprogramming and personalized medicine now allow for previously unattainable cell therapies and patient-specific modeling of PD using induced pluripotent stem cells (iPSCs). iPSCs can be selectively differentiated into a dopaminergic neuron fate naturally susceptible to neurodegeneration. In iPSC models, unlike other artificially-induced models, endogenous cellular machinery and transcriptional feedback are preserved, a fundamental step in accurately modeling this genetically complex disease. In addition to accurately modeling PD, iPSC lines can also be established with specific genetic risk factors to assess genetic sub-populations’ differing response to treatment. iPS cell lines can then be genetically corrected and subsequently transplanted back into the patient in hopes of re-establishing function. Current techniques focus on iPSCs because they are patient-specific, thereby reducing the risk of immune rejection. The year 2018 marked history as the year that the first human trial for PD iPSC transplantation began in Japan. This form of cell therapy has shown promising results in other model organisms and is currently one of our best options in slowing or even halting the progression of PD. Here, we examine the genetic contributions that have reshaped our understanding of PD, as well as the advantages and applications of iPSCs for modeling disease and personalized therapies.
Neurodegenerative diseases include a variety of pathologies such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and so forth, which share many common characteristics such as oxidative stress, glycation, abnormal protein deposition, inflammation, and progressive neuronal loss. The last century has witnessed significant research to identify mechanisms and risk factors contributing to the complex etiopathogenesis of neurodegenerative diseases, such as genetic, vascular/metabolic, and lifestyle-related factors, which often co-occur and interact with each other. Apart from several environmental or genetic factors, in recent years, much evidence hints that impairment in redox homeostasis is a common mechanism in different neurological diseases. However, from a pharmacological perspective, oxidative stress is a difficult target, and antioxidants, the only strategy used so far, have been ineffective or even provoked side effects. In this review, we report an analysis of the recent literature on the role of oxidative stress in Alzheimer’s and Parkinson’s diseases as well as in amyotrophic lateral sclerosis, retinal ganglion cells, and ataxia. Moreover, the contribution of stem cells has been widely explored, looking at their potential in neuronal differentiation and reporting findings on their application in fighting oxidative stress in different neurodegenerative diseases. In particular, the exposure to mesenchymal stem cells or their secretome can be considered as a promising therapeutic strategy to enhance antioxidant capacity and neurotrophin expression while inhibiting pro-inflammatory cytokine secretion, which are common aspects of neurodegenerative pathologies. Further studies are needed to identify a tailored approach for each neurodegenerative disease in order to design more effective stem cell therapeutic strategies to prevent a broad range of neurodegenerative disorders.
View the Study: https://pmc.ncbi.nlm.nih.gov/articles/PMC7246730
Parkinson’s disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, and as a consequence, by decreased dopamine levels in the striatum. Currently available therapies are not able to stop or reverse the progression of the disease. A novel therapeutic approach is based on cell therapy with stem cells, in order to replace degenerated neurons. Among stem cells, mesenchymal stem cells seemed the most promising thanks to their capacities to differentiate toward dopaminergic neurons and to release neurotrophic factors. Indeed, mesenchymal stem cells are able to produce different molecules with immunomodulatory, neuroprotective, angiogenic, chemotactic effects and that stimulate differentiation of resident stem cells. Mesenchymal stem cells were isolated for the first time from bone marrow, but can be collected also from adipose tissue, umbilical cord and other tissues. In this review, we focused our attention on mesenchymal stem cells derived from different sources and their application in Parkinson’s disease animal models.
View the Study: https://www.sciencedirect.com/science/article/abs/pii/S2452318616300745?via%3Dihub
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, which affects about 0.3% of the general population. As the population in the developed world ages, this creates an escalating burden on society both in economic terms and in quality of life for these patients and for the families that support them. Although currently available pharmacological or surgical treatments may significantly improve the quality of life of many patients with PD, these are symptomatic treatments that do not slow or stop the progressive course of the disease. Because motor impairments in PD largely result from loss of midbrain dopamine neurons in the substantia nigra pars compacta, PD has long been considered to be one of the most promising target diseases for cell-based therapy. Indeed, numerous clinical and preclinical studies using fetal cell transplantation have provided proof of concept that cell replacement therapy may be a viable therapeutic approach for PD. However, the use of human fetal cells as a standardized therapeutic regimen has been fraught with fundamental ethical, practical, and clinical issues, prompting scientists to explore alternative cell sources. Based on groundbreaking establishments of human embryonic stem cells and induced pluripotent stem cells, these human pluripotent stem cells have been the subject of extensive research, leading to tremendous advancement in our understanding of these novel classes of stem cells and promising great potential for regenerative medicine. In this review, we discuss the prospects and challenges of human pluripotent stem cell-based cell therapy for PD.
View the Study: https://pmc.ncbi.nlm.nih.gov/articles/PMC6077089/
Cell repair/replacing strategies for neurodegenerative diseases such as Parkinson’s disease depend on well-characterized dopaminergic neuronal candidates that are healthy and show promising effect on the rejuvenation of degenerated area of the brain. Therefore, it is imperative to develop innovative therapeutic strategies that replace damaged neurons with new/functional dopaminergic neurons. Although several research groups have reported the generation of neural precursors/neurons from human/ mouse embryonic stem cells and mesenchymal stem cells, the latter is considered to be an attractive therapeutic candidate because of its high capacity for self-renewable, no adverse effect to allogeneic versus autologous transplants, high ethical acceptance and no teratoma formation. Therefore, mesenchymal stem cells can be considered as an ideal source for replacing lost cells in degenerative diseases like Parkinson’s. Hence, the use of these cells in the differentiation of dopaminergic neurons becomes significant and thrives as a therapeutic approach to treat Parkinson’s disease. Here we highlight the basic biology of mesenchymal stem cells, their differentiation potential into dopaminergic neurons and potential use in the clinics.
View the Study: https://pubmed.ncbi.nlm.nih.gov/27842480/
