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https://www.readbyqxmd.com/read/27899629/enhanced-non-viral-gene-delivery-by-coordinated-endosomal-release-and-inhibition-of-%C3%AE-tubulin-deactylase
#1
Yoon Khei Ho, Li Han Zhou, Kam C Tam, Heng Phon Too
Efficient non-viral gene delivery is highly desirable but often unattainable with some cell-types. We report here that non-viral DNA polyplexes can efficiently transfect differentiated neuronal and stem cells. Polyplex transfection centrifugation protocols was enhanced by including a simultaneous treatment with a DOPE/CHEMS lipid suspension and a microtubule inhibitor, Tubastatin A. Lipoplex transfection protocols were not improved by this treatment. This mechanism of action was unravelled by systematically identifying and rationally mitigating barriers limiting high transfection efficiency, allowing unexpected improvements in the transfection of mesenchymal stem cells (MSC), primary neuron and several hard-to-transfect cell types beyond what are currently achievable using cationic polymers...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27886004/influence-of-surface-roughness-on-neural-differentiation-of-human-induced-pluripotent-stem-cells
#2
Zhengdong Li, Weiwei Wang, Karl Kratz, Judit Küchler, Xun Xu, Jie Zou, Deng Zijun, Xianlei Sun, Manfred Gossen, Nan Ma, Andreas Lendlein
Induced pluripotent stem cells (iPSCs) own the capacity to develop into all cell types of the adult body, presenting high potential in regenerative medicine. Regulating and controlling the differentiation of iPSCs using the surface topographic cues of biomaterials is a promising and safe approach to enhance their therapeutic efficacy. In this study, we tested the effects of surface roughness on differentiation of human iPSCs into neural progenitor cells and dopaminergic neuron cells using polystyrene with different roughness (R0: flat surface; R1: rough surface, Rq ∼ 6 μm; R2: rough surface, Rq ∼ 38 μm)...
November 23, 2016: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/27885887/cell-therapies-for-parkinson-s-disease-how-far-have-we-come
#3
Thomas B Stoker, Roger A Barker
Over the past three decades, significant progress has been made in the development of potential regenerative cell-based therapies for neurodegenerative disease, with most success being seen in Parkinson's disease. Cell-based therapies face many challenges including ethical considerations, potential for immune-mediated rejection with allogeneic and xenogeneic tissue, pathological spread of protein-related disease into the grafted tissue as well as the risk of graft overgrowth and tumorigenesis in stem cell-derived transplants...
December 2016: Regenerative Medicine
https://www.readbyqxmd.com/read/27856558/human-polymorphisms-in-nicotinic-receptors-a-functional-analysis-in-ips-derived-dopaminergic-neurons
#4
Cristina Deflorio, Stéphane Blanchard, Maria Carla Carisì, Delphine Bohl, Uwe Maskos
Tobacco smoking is a public health problem, with ∼5 million deaths per year, representing a heavy burden for many countries. No effective therapeutic strategies are currently available for nicotine addiction, and it is therefore crucial to understand the etiological and pathophysiological factors contributing to this addiction. The neuronal α5 nicotinic acetylcholine receptor (nAChR) subunit is critically involved in nicotine dependence. In particular, the human polymorphism α5D398N corresponds to the strongest correlation with nicotine dependence risk found to date in occidental populations, according to meta-analysis of genome-wide association studies...
November 17, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27842480/mesenchymal-stem-cells-as-a-source-of-dopaminergic-neurons-a-potential-cell-based-therapy-for-parkinson-s-disease
#5
Katari Venkatesh, Dwaipayan Sen
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 in 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...
November 14, 2016: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27822752/investigation-of-the-effects-of-gaba-receptor-agonists-in-the-differentiation-of-human-induced-pluripotent-stem-cells-into-dopaminergic-neurons
#6
S A Antonov, E V Novosadova, E L Arsenyeva, M A Grefenstein, A A Zykova, A G Kobylyansky, E S Manuilova, I A Grivennikov, S N Illarioshkin, N F Myasoedov
The influence of GABA receptor agonists on the terminal differentiation in vitro of dopaminergic (DA) neurons derived from IPS cells was investigated. GABA-A agonist muscimol induced transient elevation of intracellular Ca(2+) level ([Ca(2+)] i ) in the investigated cells at days 5 to 21 of differentiation. Differentiation of cells in the presence of muscimol reduced tyrosine hydroxylase expression. Thus, the presence of active GABA-A receptors, associated with phenotype determination via Ca(2+)-signalling was demonstrated in differentiating human DA neurons...
September 2016: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/27821734/role-of-sulfiredoxin-as-a-peroxiredoxin-2-denitrosylase-in-human-ipsc-derived-dopaminergic-neurons
#7
Carmen R Sunico, Abdullah Sultan, Tomohiro Nakamura, Nima Dolatabadi, James Parker, Bing Shan, Xuemei Han, John R Yates, Eliezer Masliah, Rajesh Ambasudhan, Nobuki Nakanishi, Stuart A Lipton
Recent studies have pointed to protein S-nitrosylation as a critical regulator of cellular redox homeostasis. For example, S-nitrosylation of peroxiredoxin-2 (Prx2), a peroxidase widely expressed in mammalian neurons, inhibits both enzymatic activity and protective function against oxidative stress. Here, using in vitro and in vivo approaches, we identify a role and reaction mechanism of the reductase sulfiredoxin (Srxn1) as an enzyme that denitrosylates (thus removing -SNO) from Prx2 in an ATP-dependent manner...
November 7, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27762639/stem-cells-for-modeling-and-therapy-of-parkinson-s-disease
#8
Qingxi Zhang, Wanling Chen, Sheng Tan, Tongxiang Lin
Parkinson's disease (PD) is the second most frequent neurodegenerative disease after Alzheimer's disease, which is characterized by low level of dopamine expressing in the striatum and deteriorated dopaminergic neurons (DAn) in Substantia nigra pars compacta (SNpc). Generation of PD-derived DAn including differentiation of human embryonic stem cell (hESC), human neural stem cell (hNSC), human induced pluripotent stem cell (hiPSC) and directly reprogramming provide an ideal tool to model PD, which created the possibilities of mimicking key essential pathological processes charactering single cell changes in vitro...
October 20, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27739432/purification-of-functional-human-es-and-ipsc-derived-midbrain-dopaminergic-progenitors-using-lrtm1
#9
Bumpei Samata, Daisuke Doi, Kaneyasu Nishimura, Tetsuhiro Kikuchi, Akira Watanabe, Yoshimasa Sakamoto, Jungo Kakuta, Yuichi Ono, Jun Takahashi
Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (mDA) neurons for cell replacement therapy for Parkinson's disease (PD). However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. To eliminate these unwanted cells, cell sorting using antibodies for specific markers such as CORIN or ALCAM has been developed, but neither marker is specific for ventral midbrain. Here we employ a double selection strategy for cells expressing both CORIN and LMX1A::GFP, and report a cell surface marker to enrich mDA progenitors, LRTM1...
October 14, 2016: Nature Communications
https://www.readbyqxmd.com/read/27725851/bmp2-promotes-the-differentiation-of-neural-stem-cells-into-dopaminergic-neurons-in-vitro-via-mir-145-mediated-upregulation-of-nurr1-expression
#10
Wang Yan, Zhao-Ying Chen, Jia-Qi Chen, Hui-Min Chen
BACKGROUND: Neural stem cells (NSCs) are pluripotent and self-renewing cells which could differentiate into diverse types of neural cells, such as dopaminergic (DA) neurons, the loss of which is the typical characteristic of Parkinson's disease (PD). This study aimed to examine the molecular mechanisms of BMP2-mediating NSCs differentiation into DA neurons. METHODS: Different concentrations of BMP2 were used to induce the differentiation of NSCs into DA neurons, which were characterized by the number and the neurite lengths of tyrosine hydroxylase (TH)+ and dopamine transporter (DAT)+ neurons by immunocytochemistry...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27720902/targeted-differentiation-of-regional-ventral-neuroprogenitors-and-related-neuronal-subtypes-from-human-pluripotent-stem-cells
#11
Liankai Chi, Beibei Fan, Kunshan Zhang, Yanhua Du, Zhongliang Liu, Yujiang Fang, Zhenyu Chen, Xudong Ren, Xiangjie Xu, Cizhong Jiang, Siguang Li, Lin Ma, Liang Gao, Ling Liu, Xiaoqing Zhang
Embryoid body (EB) formation and adherent culture (AD) paradigms are equivalently thought to be applicable for neural specification of human pluripotent stem cells. Here, we report that sonic hedgehog-induced ventral neuroprogenitors under EB conditions are fated to medial ganglionic eminence (MGE), while the AD cells mostly adopt a floor-plate (FP) fate. The EB-MGE later on differentiates into GABA and cholinergic neurons, while the AD-FP favors dopaminergic neuron specification. Distinct developmental, metabolic, and adhesion traits in AD and EB cells may potentially account for their differential patterning potency...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27720638/genetic-modification-of-h2ax-renders-mesenchymal-stromal-cell-derived-dopamine-neurons-more-resistant-to-dna-damage-and-subsequent-apoptosis
#12
Peizhou Jiang, Peng Huang, Shu-Hui Yen, Abba C Zubair, Dennis W Dickson
BACKGROUND AIMS: Aberrant production of reactive oxygen species (ROS) and its impact on the integrity of genomic DNA have been considered one of the major risk factors for the loss of dopaminergic neurons in Parkinson's disease (PD). Stem cell transplantation as a strategy to replenish new functional neurons has great potential for PD treatment. However, limited survival of stem cells post-transplantation has always been an obstacle ascribed to the existence of neurotoxic environment in PD patients...
October 6, 2016: Cytotherapy
https://www.readbyqxmd.com/read/27716510/molecular-diversity-of-midbrain-development-in-mouse-human-and-stem-cells
#13
Gioele La Manno, Daniel Gyllborg, Simone Codeluppi, Kaneyasu Nishimura, Carmen Salto, Amit Zeisel, Lars E Borm, Simon R W Stott, Enrique M Toledo, J Carlos Villaescusa, Peter Lönnerberg, Jesper Ryge, Roger A Barker, Ernest Arenas, Sten Linnarsson
Understanding human embryonic ventral midbrain is of major interest for Parkinson's disease. However, the cell types, their gene expression dynamics, and their relationship to commonly used rodent models remain to be defined. We performed single-cell RNA sequencing to examine ventral midbrain development in human and mouse. We found 25 molecularly defined human cell types, including five subtypes of radial glia-like cells and four progenitors. In the mouse, two mature fetal dopaminergic neuron subtypes diversified into five adult classes during postnatal development...
October 6, 2016: Cell
https://www.readbyqxmd.com/read/27666790/development-and-dynamic-regulation-of-mitochondrial-network-in-human-midbrain-dopaminergic-neurons-differentiated-from-ipscs
#14
Du Fang, Yu Qing, Shijun Yan, Doris Chen, Shirley ShiDu Yan
Mitochondria are critical to neurogenesis, but the mechanisms of mitochondria in neurogenesis have not been well explored. We fully characterized mitochondrial alterations and function in relation to the development of human induced pluripotent stem cell (hiPSC)-derived dopaminergic (DA) neurons. Following directed differentiation of hiPSCs to DA neurons, mitochondria in these neurons exhibit pronounced changes during differentiation, including mature neurophysiology characterization and functional synaptic network formation...
October 11, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27659216/impact-of-the-secretome-of-human-mesenchymal-stem-cells-on-brain-structure-and-animal-behavior-in-a-rat-model-of-parkinson-s-disease
#15
Fábio G Teixeira, Miguel M Carvalho, Krishna M Panchalingam, Ana J Rodrigues, Bárbara Mendes-Pinheiro, Sandra Anjo, Bruno Manadas, Leo A Behie, Nuno Sousa, António J Salgado
: : Research in the last decade strongly suggests that mesenchymal stem cell (MSC)-mediated therapeutic benefits are mainly due to their secretome, which has been proposed as a possible therapeutic tool for the treatment of Parkinson's disease (PD). Indeed, it has been shown that the MSC secretome increases neurogenesis and cell survival, and has numerous neuroprotective actions under different conditions. Additionally, using dynamic culturing conditions (through computer-controlled bioreactors) can further modulate the MSC secretome, thereby generating a more potent neurotrophic factor cocktail (i...
September 22, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27640816/dopaminergic-neurons-differentiating-from-lrrk2-g2019s-induced-pluripotent-stem-cells-show-early-neuritic-branching-defects
#16
Laurence Borgs, Elise Peyre, Philippe Alix, Kevin Hanon, Benjamin Grobarczyk, Juliette D Godin, Audrey Purnelle, Nathalie Krusy, Pierre Maquet, Philippe Lefebvre, Vincent Seutin, Brigitte Malgrange, Laurent Nguyen
Some mutations of the LRRK2 gene underlie autosomal dominant form of Parkinson's disease (PD). The G2019S is a common mutation that accounts for about 2% of PD cases. To understand the pathophysiology of this mutation and its possible developmental implications, we developed an in vitro assay to model PD with human induced pluripotent stem cells (hiPSCs) reprogrammed from skin fibroblasts of PD patients suffering from the LRKK2 G2019S mutation. We differentiated the hiPSCs into neural stem cells (NSCs) and further into dopaminergic neurons...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27635198/mesenchymal-stem-cells-that-located-in-the-electromagnetic-fields-improves-rat-model-of-parkinson-s-disease
#17
Majid Jadidi, Saeed Moghadas Biat, Hamid Reza Sameni, Manouchehr Safari, Abbas Ali Vafaei, Laya Ghahari
OBJECTIVES: The main characteristic of mesenchymal stem cells (MSCs) is their ability to produce other cell types. Electromagnetic field (EMF) stimulates differentiation of MSCs into other cells. In this study, we investigated whether EMF can effect on the differentiation of MSCs into dopaminergic (DA) neurons. MATERIALS AND METHODS: An EMF with a frequency of 50 Hz and two intensities of 40 and 400 µT 1hr/day was generated around the cells for a week. Afterwards, these cells were injected into the left ventricle of Parkinsonian rats...
July 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27622596/advantages-of-nonhuman-primates-as-preclinical-models-for-evaluating-stem-cell-based-therapies-for-parkinson-s-disease
#18
Douglas A Grow, John R McCarrey, Christopher S Navara
The derivation of dopaminergic neurons from induced pluripotent stem cells brings new hope for a patient-specific, stem cell-based replacement therapy to treat Parkinson's disease (PD) and related neurodegenerative diseases; and this novel cell-based approach has already proven effective in animal models. However, there are several aspects of this procedure that have yet to be optimized to the extent required for translation to an optimal cell-based transplantation protocol in humans. These challenges include pinpointing the optimal graft location, appropriately scaling up the graft volume, and minimizing the risk of chronic immune rejection, among others...
August 26, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27618265/cell-class-lineage-analysis-reveals-sexually-dimorphic-lineage-compositions-in-the-drosophila-brain
#19
Qingzhong Ren, Takeshi Awasaki, Yu-Fen Huang, Zhiyong Liu, Tzumin Lee
The morphology and physiology of neurons are directed by developmental decisions made within their lines of descent from single stem cells. Distinct stem cells may produce neurons having shared properties that define their cell class, such as the type of secreted neurotransmitter. The relationship between cell class and lineage is complex. Here we developed the transgenic cell class-lineage intersection (CLIn) system to assign cells of a particular class to specific lineages within the Drosophila brain. CLIn also enables birth-order analysis and genetic manipulation of particular cell classes arising from particular lineages...
October 10, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27615060/evaluation-of-the-rotenone-induced-activation-of-the-nrf2-pathway-in-a-neuronal-model-derived-from-human-induced-pluripotent-stem-cells
#20
Dimitra Zagoura, David Canovas-Jorda, Francesca Pistollato, Susanne Bremer-Hoffmann, Anna Bal-Price
Human induced pluripotent stem cells (hiPSCs) are considered as a powerful tool for drug and chemical screening and development of new in vitro testing strategies in the field of toxicology, including neurotoxicity evaluation. These cells are able to expand and efficiently differentiate into different types of neuronal and glial cells as well as peripheral neurons. These human cells-based neuronal models serve as test systems for mechanistic studies on different pathways involved in neurotoxicity. One of the well-known mechanisms that are activated by chemically-induced oxidative stress is the Nrf2 signalling pathway...
September 8, 2016: Neurochemistry International
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