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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/28627367/nrf2-pathway-activation-upon-rotenone-treatment-in-human-ipsc-derived-neural-stem-cells-undergoing-differentiation-towards-neurons-and-astrocytes
#2
Francesca Pistollato, David Canovas-Jorda, Dimitra Zagoura, Anna Bal-Price
Activation of Nrf2/ARE signaling pathway occurs ubiquitously in most cell types upon induction of oxidative stress. Rotenone, an inhibitor of mitochondrial complex I, can be used to trigger oxidative stress, stimulate the activation of Nrf2 pathway in neuronal and astrocytic cells and assess neurotoxicity. We have previously demonstrated that an acute treatment with rotenone can induce Nrf2 activation, which leads to astrocyte activation and dopaminergic (DA) neuronal cell death in a mixed neuronal/astrocytic cell model derived from human induced pluripotent stem cells (hiPSCs)...
June 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28585381/modeling-parkinson-s-disease-with-induced-pluripotent-stem-cells-harboring-%C3%AE-synuclein-mutations
#3
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
#4
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/28557659/geminin-participates-in-differentiation-decisions-of-adult-neural-stem-cells-transplanted-in-the-hemiparkinsonian-mouse-brain
#5
Ioanna Taouki, Eve Tasiudi, Maria-Eleni Lalioti, Christina Kyrousi, Eleni Skavatsou, Konstantina Kaplani, Zoi Lygerou, Elias D Kouvelas, Adamantia Mitsacos, Panagiotis Giompres, Stavros Taraviras
Neural stem cells have been considered as a source of stem cells that can be used for cell replacement therapies in neurodegenerative diseases, as they can be isolated and expanded in vitro and can be used for autologous grafting. However, due to low percentages of survival and varying patterns of differentiation, strategies that will enhance the efficacy of transplantation are under scrutiny. Here, we have examined whether alterations in Geminin's expression, a protein that coordinates the balance between self-renewal and differentiation, can improve the properties of stem cells transplanted in 6 OHDA hemiparkinsonian mouse model...
May 30, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28552230/strategies-for-bringing-stem-cell-derived-dopamine-neurons-to-the-clinic-the-kyoto-trial
#6
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/28552228/strategies-for-bringing-stem-cell-derived-dopamine-neurons-to-the-clinic-a-european-approach-stem-pd
#7
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
#8
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
#9
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
#10
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/28520507/gold-nanoparticles-enhance-the-differentiation-of-embryonic-stem-cells-into-dopaminergic-neurons-via-mtor-p70s6k-pathway
#11
Min Wei, Song Li, Zhaofei Yang, Wei Zheng, Weidong Le
AIM: This study aimed to investigate the effect of gold nanoparticles (AuNPs) on differentiation of mouse embryonic stem cells (ESCs) into dopaminergic (DA) neurons and explore the possible underlying molecular mechanisms. MATERIALS & METHODS: The efficiency of AuNPs on DA neuron differentiation was evaluated by observing fluorescence in TH promoter-engineered GFP-reporter ESCs, western blot and real-time PCR. The possible signal pathway was determined by western blot...
May 18, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28505596/engineered-hydrogels-increase-the-post-transplantation-survival-of-encapsulated-hesc-derived-midbrain-dopaminergic-neurons
#12
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/28484750/in-vitro-field-potential-monitoring-on-a-multi-microelectrode-array-for-the-electrophysiological-long-term-screening-of-neural-stem-cell-maturation
#13
Diana Seidel, Heinz-Georg Jahnke, Beate Englich, Mathilde Girard, Andrea A Robitzki
Due to the lack of appropriate cell models as well as automated electrophysiology monitoring technologies, the standardized identification of neurotoxic or protective effects in vitro remains a major problem in today's pharmaceutical ingredient development. Over the past few years, in vivo-like human pluripotent stem cell-derived neuronal networks have turned out to be a promising physiological cell source, if the establishment of robust and time-saving functional maturation strategies based on stable and expandable neural progenitor populations can be achieved...
May 9, 2017: Analyst
https://www.readbyqxmd.com/read/28482609/combining-nt3-overexpressing-mscs-and-plga-microcarriers-for-brain-tissue-engineering-a-potential-tool-for-treatment-of-parkinson-s-disease
#14
Hanieh Moradian, Hamid Keshvari, Hamidreza Fasehee, Rassoul Dinarvand, Shahab Faghihi
Parkinson's disease (PD) is a progressive neurodegenerative disorder that characterized by destruction of substantia nigrostriatal pathway due to the loss of dopaminergic (DA) neurons. Regardless of substantial efforts for treatment of PD in recent years, an effective therapeutic strategy is still missing. In a multidisciplinary approach, bone marrow derived mesenchymal stem cells (BMSCs) are genetically engineered to overexpress neurotrophin-3 (nt-3 gene) that protect central nervous system tissues and stimulates neuronal-like differentiation of BMSCs...
July 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28472853/genetic-rescue-of-mitochondrial-and-skeletal-muscle-impairment-in-an-induced-pluripotent-stem-cells-model-of-coenzyme-q10-deficiency
#15
Damià Romero-Moya, Carlos Santos-Ocaña, Julio Castaño, Gloria Garrabou, José A Rodríguez-Gómez, Vanesa Ruiz-Bonilla, Clara Bueno, Patricia González-Rodríguez, Alessandra Giorgetti, Eusebio Perdiguero, Cristina Prieto, Constanza Moren-Nuñez, Daniel J Fernández-Ayala, Maria Victoria Cascajo, Iván Velasco, Josep Maria Canals, Raquel Montero, Delia Yubero, Cristina Jou, José López-Barneo, Francesc Cardellach, Pura Muñoz-Cánoves, Rafael Artuch, Plácido Navas, Pablo Menendez
Coenzyme Q10 (CoQ10 ) plays a crucial role in mitochondria as an electron carrier within the mitochondrial respiratory chain (MRC) and is an essential antioxidant. Mutations in genes responsible for CoQ10 biosynthesis (COQ genes) cause primary CoQ10 deficiency, a rare and heterogeneous mitochondrial disorder with no clear genotype-phenotype association, mainly affecting tissues with high-energy demand including brain and skeletal muscle (SkM). Here, we report a four-year-old girl diagnosed with minor mental retardation and lethal rhabdomyolysis harboring a heterozygous mutation (c...
May 4, 2017: Stem Cells
https://www.readbyqxmd.com/read/28469646/neural-grafting-for-parkinson-s-disease-challenges-and-prospects
#16
REVIEW
Thomas B Stoker, Nicholas F Blair, Roger A Barker
Parkinson's disease (PD) is a neurodegenerative condition which causes a characteristic movement disorder secondary to loss of dopaminergic neurons in the substanitia nigra. The motor disorder responds well to dopamine-replacement therapies, though these result in significant adverse effects due to non-physiological release of dopamine in the striatum, and off-target effects. Cell-based regenerative treatments offer a potential means for targeted replacement of dopamine, in a physiological manner. Dopaminergic neurons for cell-based therapies can be obtained from several sources...
March 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28467897/dopamine-induces-oscillatory-activities-in-human-midbrain-neurons-with-parkin-mutations
#17
Ping Zhong, Zhixing Hu, Houbo Jiang, Zhen Yan, Jian Feng
Locomotor symptoms in Parkinson's disease (PD) are accompanied by widespread oscillatory neuronal activities in basal ganglia. Here, we show that activation of dopamine D1-class receptors elicits a large rhythmic bursting of spontaneous excitatory postsynaptic currents (sEPSCs) in midbrain neurons differentiated from induced pluripotent stem cells (iPSCs) of PD patients with parkin mutations, but not normal subjects. Overexpression of wild-type parkin, but not its PD-causing mutant, abolishes the oscillatory activities in patient neurons...
May 2, 2017: Cell Reports
https://www.readbyqxmd.com/read/28466824/mesenchymal-stem-cell-therapy-in-parkinson-s-disease-animal-models
#18
REVIEW
A Gugliandolo, P Bramanti, E Mazzon
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...
December 2, 2016: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/28457671/old-and-new-challenges-in-parkinson-s-disease-therapeutics
#19
REVIEW
Ana O Pires, F G Teixeira, B Mendes-Pinheiro, Sofia C Serra, Nuno Sousa, António J Salgado
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and/or loss od neuronal projections, in several dopaminergic networks. Current treatments for idiopathic PD rely mainly on the use of pharmacologic agents to improve motor symptomatology of PD patients. Nevertheless, so far PD remains an incurable disease. Therefore, it is of utmost importance to establish new therapeutic strategies for PD treatment. Over the last 20 years, several molecular, gene and cell/stem-cell therapeutic approaches have been developed with the aim of counteracting or retarding PD progression...
April 27, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28452458/chiro-optical-modulation-for-nurr1-production-from-stem-cells
#20
Madhumita Patel, Hyo Jung Moon, Ja Hye Hong, Byeongmoon Jeong
Nuclear receptor related 1 (NURR1) is an essential protein for maintenance of dopaminergic neurons in adult midbrain of which deficiency leads to Parkinson's disease. To enhance the NURR1 production of neural cells, various approaches are under investigation. Here we report that NURR1 is highly expressed in stem cells by exposure to an L-polarized blue light emitting diode (LED). Compared to stem cells cultured in the absence of a LED, under polarized green and red LEDs, the stem cells exposed to a polarized blue LED significantly enhanced neuronal biomarkers such as neurofilament M (NFM) and neuron specific enolase (NSE) at both mRNA and protein levels...
May 2, 2017: ACS Chemical Neuroscience
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