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Parkinson disease and stem cell

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https://www.readbyqxmd.com/read/28635509/induced-pluripotent-stem-cell-derived-dopaminergic-neurons-from-adult-common-marmoset-fibroblasts
#1
Scott C Vermilyea, Scott Guthrie, Michael Meyer, Kim Smuga-Otto, Katarina Braun, Sara Howden, James A Thomson, Su-Chun Zhang, Marina Emborg, Dr Thaddeus G Golos
The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter lifespan compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties including development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers...
June 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28592657/induced-pluripotent-stem-cell-models-of-lysosomal-storage-disorders
#2
REVIEW
Daniel K Borger, Benjamin McMahon, Tamanna Roshan Lal, Jenny Serra-Vinardell, Elma Aflaki, Ellen Sidransky
Induced pluripotent stem cells (iPSCs) have provided new opportunities to explore the cell biology and pathophysiology of human diseases, and the lysosomal storage disorder research community has been quick to adopt this technology. Patient-derived iPSC models have been generated for a number of lysosomal storage disorders, including Gaucher disease, Pompe disease, Fabry disease, metachromatic leukodystrophy, the neuronal ceroid lipofuscinoses, Niemann-Pick types A and C1, and several of the mucopolysaccharidoses...
June 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28591653/a-highly-efficient-human-pluripotent-stem-cell-microglia-model-displays-a-neuronal-co-culture-specific-expression-profile-and-inflammatory-response
#3
Walther Haenseler, Stephen N Sansom, Julian Buchrieser, Sarah E Newey, Craig S Moore, Francesca J Nicholls, Satyan Chintawar, Christian Schnell, Jack P Antel, Nicholas D Allen, M Zameel Cader, Richard Wade-Martins, William S James, Sally A Cowley
Microglia are increasingly implicated in brain pathology, particularly neurodegenerative disease, with many genes implicated in Alzheimer's, Parkinson's, and motor neuron disease expressed in microglia. There is, therefore, a need for authentic, efficient in vitro models to study human microglial pathological mechanisms. Microglia originate from the yolk sac as MYB-independent macrophages, migrating into the developing brain to complete differentiation. Here, we recapitulate microglial ontogeny by highly efficient differentiation of embryonic MYB-independent iPSC-derived macrophages then co-culture them with iPSC-derived cortical neurons...
June 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28589443/metformin-a-future-therapy-for-neurodegenerative-diseases
#4
REVIEW
Magdalena Markowicz-Piasecka, Joanna Sikora, Aleksandra Szydłowska, Agata Skupień, Elżbieta Mikiciuk-Olasik, Kristiina M Huttunen
Type 2 diabetes mellitus (T2DM) is a complex, chronic and progressive metabolic disease, which is characterized by relative insulin deficiency, insulin resistance, and high glucose levels in blood. Esteemed published articles and epidemiological data exhibit an increased risk of developing Alzheimer's disease (AD) in diabetic pateints. Metformin is the most frequently used oral anti-diabetic drug, which apart from hypoglycaemic activity, improves serum lipid profiles, positively influences the process of haemostasis, and possesses anti-inflammatory properties...
June 6, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28585381/modeling-parkinson-s-disease-with-induced-pluripotent-stem-cells-harboring-%C3%AE-synuclein-mutations
#5
Karamjit Singh Dolt, Fella Hammachi, Tilo Kunath
Parkinson's disease (PD) is a common neurodegenerative condition affecting more than 8 million people worldwide. Although, the majority of PD cases are sporadic in nature, there are a growing number of monogenic mutations identified to cause PD in a highly penetrant manner. Many of these familial mutations give rise to a condition that is clinically and neuropathologically similar, if not identical, to sporadic PD. Mutations in genes such as SNCA cause PD in an autosomal dominant manner and patients have motor and non-motor symptoms that are typical for sporadic PD...
July 2017: Brain Pathology
https://www.readbyqxmd.com/read/28580639/mesenchymal-stem-cells-stabilize-axonal-transports-for-autophagic-clearance-of-%C3%AE-synuclein-in-parkinsonian-models
#6
Se Hee Oh, Seok Cheol Lee, Dong Yeol Kim, Ha Na Kim, Jin Young Shin, Byoung Seok Ye, Phil Hyu Lee
Genome-wide association studies have identified two loci, SNCA and the microtubule (MT)-associated protein tau, as common risk factors for Parkinson's disease (PD). Specifically, α-synuclein directly destabilizes MT via tau phosphorylation and induces axonal transport deficits that are the primary events leading to an abnormal accumulation of α-synuclein that causes nigral dopaminergic cell loss. In the present study, we demonstrated that mesenchymal stem cells (MSCs) could modulate cytoskeletal networks and trafficking to exert neuroprotective properties in wild-type or A53T α-synuclein overexpressing cells and mice...
June 5, 2017: Stem Cells
https://www.readbyqxmd.com/read/28579395/cryopreservation-maintains-functionality-of-human-ipsc-dopamine-neurons-and-rescues-parkinsonian-phenotypes-in%C3%A2-vivo
#7
Dustin R Wakeman, Benjamin M Hiller, David J Marmion, Christopher W McMahon, Grant T Corbett, Kile P Mangan, Junyi Ma, Lauren E Little, Zhong Xie, Tamara Perez-Rosello, Jaime N Guzman, D James Surmeier, Jeffrey H Kordower
A major challenge for clinical application of pluripotent stem cell therapy for Parkinson's disease (PD) is large-scale manufacturing and cryopreservation of neurons that can be efficiently prepared with minimal manipulation. To address this obstacle, midbrain dopamine neurons were derived from human induced pluripotent stem cells (iPSC-mDA) and cryopreserved in large production lots for biochemical and transplantation studies. Cryopreserved, post-mitotic iPSC-mDA neurons retained high viability with gene, protein, and electrophysiological signatures consistent with midbrain floor-plate lineage...
May 22, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28552237/ex-vivo-gene-therapy-for-the-treatment-of-neurological-disorders
#8
Genevieve Gowing, Soshana Svendsen, Clive N Svendsen
Ex vivo gene therapy involves the genetic modification of cells outside of the body to produce therapeutic factors and their subsequent transplantation back into patients. Various cell types can be genetically engineered. However, with the explosion in stem cell technologies, neural stem/progenitor cells and mesenchymal stem cells are most often used. The synergy between the effect of the new cell and the additional engineered properties can often provide significant benefits to neurodegenerative changes in the brain...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/28552233/advanced-imaging-of-transplant-survival-fate-differentiation-and-integration
#9
Nadja Van Camp, Elsa Diguet, Philippe Hantraye
Stem cell-based therapy trials for the treatment of neurodegenerative diseases such as Parkinson's and Huntington's disease are being actively prepared both at the preclinical and clinical level. Preclinical validation of these stem cell transplantations necessitates to implement a translational continuum to take one pluripotent stem cell through the point of "first-in-man" clinical trial. Main steps along this translational continuum include stem cell GMP production, in vitro optimization of differentiation protocols necessary to direct stem cells to the desired neuronal phenotype, and evaluation of functional efficacy in animal models including large animal models...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/28552230/strategies-for-bringing-stem-cell-derived-dopamine-neurons-to-the-clinic-the-kyoto-trial
#10
Jun Takahashi
Concerted efforts are realizing cell-based therapy for Parkinson's disease (PD). In this chapter, I describe efforts at the Center for iPS Cell Research and Application (CiRA), Kyoto University. These efforts use induced pluripotent stem cells (iPSCs) as donor cells. The iPSCs were established as human leukocyte antigen homozygous at CiRA and are intended for allogeneic transplantation. Our manufacturing protocol includes a feeder-free cell culture with laminin fragment LM511-E8 and the sorting of CORIN(+) cells...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/28552229/strategies-for-bringing-stem-cell-derived-dopamine-neurons-to-the-clinic-the-nystem-trial
#11
Lorenz Studer
Over the last 10 years, there has been significant progress in defining culture conditions to derive bona fide human midbrain dopamine (mDA) neurons from human embryonic stem cells or from human-induced pluripotent stem cells, two cell sources referred to as human pluripotent stem cells (hPSCs). Those developments have made it possible to manufacture mDA neurons with at sufficient scale and precision to contemplate their use in cell replacement therapy for the treatment of Parkinson's disease. Our group is one of the several teams that are in the process of initiating the first human clinical trials based on the use of mDA neurons derived from hPSCs...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/28552228/strategies-for-bringing-stem-cell-derived-dopamine-neurons-to-the-clinic-a-european-approach-stem-pd
#12
Agnete Kirkeby, Malin Parmar, Roger A Barker
The treatment of Parkinson's disease (PD) has for over 50 years relied on dopaminergic therapies that are highly effective especially in the early years of the condition, but ultimately are limited by the development of side effects that relate to the nonphysiological stimulation of dopamine receptors including in nonstriatal areas. Targeted regenerative therapies designed to restore specifically the lost dopaminergic innervation of the striatum would therefore represent a major advance in treating PD. Transplantation of human fetal ventral midbrain tissue to the striatum of PD patients has provided proof-of-principle that such an approach can provide long-term clinical benefits with a reduced dependency on any oral dopaminergic agents...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/28552226/preparation-characterization-and-banking-of-clinical-grade-cells-for-neural-transplantation-scale-up-fingerprinting-and-genomic-stability-of-stem-cell-lines
#13
Ammar Natalwala, Tilo Kunath
Parkinson's disease is a complex and progressive neurodegenerative condition that is characterized by the severe loss of midbrain dopaminergic (mDA) neurons, which innervate the striatum. Cell transplantation therapies to rebuild this dopaminergic network have been attempted for over 30 years. The most promising outcomes were observed when human fetal mesencephalic tissue was used as the source of cells for transplantation. However, reliance on terminations for a Parkinson's therapy presents significant logistical and ethical hurdles...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/28547771/translation-of-wnt-developmental-programs-into-stem-cell-replacement-strategies-for-the-treatment-of-parkinson-s-disease
#14
REVIEW
Enrique M Toledo, Daniel Gyllborg, Ernest Arenas
Wnt signalling is a highly conserved pathway across species that is critical for normal development and is deregulated in multiple diseases including cancer and neurodegeneration. Wnt signalling is critically required for midbrain dopaminergic (mDA) neuron development and maintenance. Understanding the molecular processes controlled by Wnt signalling may thus hold the key to understand the physiopathology and to develop novel therapies aimed at preventing the loss of mDA neurons in Parkinson's disease (PD)...
May 26, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28541509/evidence-that-phosphorylated-ubiquitin-signaling-is-involved-in-the-etiology-of-parkinson-s-disease
#15
Kahori Shiba-Fukushima, Kei-Ichi Ishikawa, Tsuyoshi Inoshita, Nana Izawa, Masashi Takanashi, Shigeto Sato, Osamu Onodera, Wado Akamatsu, Hideyuki Okano, Yuzuru Imai, Nobutaka Hattori
The ubiquitin (Ub) kinase PINK1 and the E3 Ub ligase Parkin, two gene products associated with young-onset Parkinson's disease (PD), participate in mitochondrial quality control. The phosphorylation of mitochondrial polyUb by PINK1, which is activated in a mitochondrial membrane potential (ΔΨm)-dependent manner, facilitates the mitochondrial translocation and concomitant enzymatic activation of Parkin, leading to the clearance of phospho-polyUb-tagged mitochondria via mitophagy. Thus, Ub phosphorylation is a key event in PINK1-Parkin-mediated mitophagy...
May 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28533935/a-review-of-the-emerging-potential-therapy-for-neurological-disorders-human-embryonic-stem-cell-therapy
#16
REVIEW
Geeta Shroff, Jyoti Dhanda Titus, Rhea Shroff
The first human embryonic stem cell (hESC) line was developed in the late nineties. hESCs are capable of proliferating indefinitely and differentiate into all the three embryonic germ layers. Further, the differentiation of hESC lines into neural precursor cells and neurons, astrocytes and oligodendrocytes showed their potential in treating several incurable neurological disorders such as spinal cord injury (SCI), cerebral palsy (CP), Parkinson's disease (PD). In this review, we will discuss the global scenario of research and therapeutic use of hESCs in the treatment of neurological disorders...
2017: American Journal of Stem Cells
https://www.readbyqxmd.com/read/28523560/stem-cell-technology-for-epi-genetic-brain-disorders
#17
Renzo J M Riemens, Edilene S Soares, Manel Esteller, Raul Delgado-Morales
Despite the enormous efforts of the scientific community over the years, effective therapeutics for many (epi)genetic brain disorders remain unidentified. The common and persistent failures to translate preclinical findings into clinical success are partially attributed to the limited efficiency of current disease models. Although animal and cellular models have substantially improved our knowledge of the pathological processes involved in these disorders, human brain research has generally been hampered by a lack of satisfactory humanized model systems...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28509081/interleukin-6-mediated-induced-pluripotent-stem-cell-ipsc-derived-neural-differentiation
#18
Yanuar Alan Sulistio, Han Kyu Lee, Sung Jun Jung, Klaus Heese
In an aging society with an increasing threat to higher brain cognitive functions due to dementia, it becomes imperative to identify new molecular remedies for supporting adult neurogenesis. Interleukin-6 (IL-6) is a promising cytokine that can support neurogenesis under conditions of neurodegeneration, and neuron replacement is eventually possible due to its agonistic acting soluble receptor sIL-6R. Here, we report that activation of the IL-6-signal transducer and activator of transcription 3 (STAT3) axis is neurogenic and has potential therapeutic applications for the treatment of neurodegenerative diseases such as Parkinson's disease (PD)...
May 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28505596/engineered-hydrogels-increase-the-post-transplantation-survival-of-encapsulated-hesc-derived-midbrain-dopaminergic-neurons
#19
Maroof M Adil, Tandis Vazin, Badriprasad Ananthanarayanan, Gonçalo M C Rodrigues, Antara T Rao, Rishikesh U Kulkarni, Evan W Miller, Sanjay Kumar, David V Schaffer
Cell replacement therapies have broad biomedical potential; however, low cell survival and poor functional integration post-transplantation are major hurdles that hamper clinical benefit. For example, following striatal transplantation of midbrain dopaminergic (mDA) neurons for the treatment of Parkinson's disease (PD), only 1-5% of the neurons typically survive in preclinical models and in clinical trials. In general, resource-intensive generation and implantation of larger numbers of cells are used to compensate for the low post-transplantation cell-survival...
May 5, 2017: Biomaterials
https://www.readbyqxmd.com/read/28490211/aav-vectors-and-stem-cells-friends-or-foes
#20
Nolan Brown, Liujiang Song, Nageswara Rao Kollu, Matt Hirsch
The infusion of healthy stem cells into a patient, termed stem cell therapy, has shown great promise for the treatment of genetic and non-genetic diseases including mucopolysaccharidosis type 1, Parkinson's disease, multiple sclerosis, numerous immunodeficiency disorders, and aplastic anemia. Stem cells for cell therapy can be collected from the patient (autologous) or collected from another "healthy" individual (allogeneic). The use of allogenic stem cells is accompanied with the potentially fatal risk that the transplanted donor T cells will reject the patient's cells, a process termed graft-versus-host disease...
May 10, 2017: Human Gene Therapy
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