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dopaminergic stem cells

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https://www.readbyqxmd.com/read/29450981/nurr1-promotes-neurogenesis-of-dopaminergic-neuron-and-represses-inflammatory-factors-in-the-transwell-coculture-system-of-neural-stem-cells-and-microglia
#1
Xiaoxiang Chen, Yuan Qian, Xiangpeng Wang, Zhiwei Tang, Jiaotian Xu, Hai Lin, Zhiyong Yang, Xiaobin Song, Di Lu, Jiazhi Guo, Ligong Bian, Yu Li, Lei Zhou, Xingli Deng
INTRODUCTION: Neural stem cells (NSCs) are the most promising cells for cell replacement therapy for Parkinson's disease (PD). However, a majority of the transplanted NSCs differentiated into glial cells, thereby limiting the clinical application. Previous studies indicated that chronic neuroinflammation plays a vital role in the degeneration of midbrain DA (mDA) neurons, which suggested the developing potential of therapies for PD by targeting the inflammatory processes. Thus, Nurr1 (nuclear receptor-related factor 1), a transcription factor, has been referred to play a pivotal role in both the differentiation of dopaminergic neurons in embryonic stages and the maintenance of the dopaminergic phenotype throughout life...
February 15, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29428530/rotenone-exerts-developmental-neurotoxicity-in-a-human-brain-spheroid-model
#2
David Pamies, Katharina Block, Pierre Lau, Laura Gribaldo, Carlos Pardo, Paula Barreras, Lena Smirnova, Daphne Wiersma, Liang Zhao, Georgina Harris, Thomas Hartung, Helena T Hogberg
Growing concern suggests that some chemicals exert (developmental) neurotoxicity (DNT and NT) and are linked to the increase in incidence of autism, attention deficit and hyperactivity disorders. The high cost of routine tests for DNT and neurotoxicity (NT) assessment make it difficult to test the high numbers of existing chemicals. Thus, more cost effective neurodevelopmental models are needed. The use of induced pluripotent stem cells (iPSC) in combination with the emerging human 3D tissue culture platforms, present a novel tool to predicting and study human toxicity...
February 8, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29416637/liver-x-receptors-agonist-promotes-differentiation-of-rat-bone-marrow-derived-mesenchymal-stem-cells-into-dopaminergic-neuron-like-cells
#3
Oumei Cheng, Xiaoyan Tian, Ying Luo, Shaoshan Mai, Yang Yang, Shengnan Kuang, Qi Chen, Jie Ma, Beibei Chen, Rong Li, Lu Yang, Huan Li, Congli Hu, Jiahua Zhang, Zhihao Chen, Yuke Li, Hui Xia, Ying Xu, Junqing Yang
Dopaminergic (DA) neurons derived from bone marrow derived mesenchymal stem cells (BMSCs) maybe a valuable source for cell replacement therapy in Parkinson disease. Recent studies showed that new functions of LXR and their ligands have been proposed to prevent PD in the adult nervous system. The present study was designed to observe the effect of liver X receptors (LXR) agonist on differentiation of rat BMSCs into DA neurons. Expressions of the neuronal markers (Tuj1 and Nestin), the specific marker of DA neurons (tyrosine hydroxylase, TH), LXR α and LXR β were measured by immunocytochemical assay and TH/Tuj1 positive cells were determined by quantitative cell count analyses...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29411538/spion-mediated-mir-141-promotes-the-differentiation-of-huaescs-into-dopaminergic-neuron-like-cells-via-suppressing-lncrna-hotair
#4
Te Liu, Hu Zhang, Jiajia Zheng, Jiajia Lin, Yongyi Huang, Jiulin Chen, Zhihua Yu, Lihe Guo, Weidong Pan, Ying Xiong, Chuan Chen
In this study, a bioinformatics analysis and luciferase reporter assay revealed that microRNA-141 could silence the expression of lncRNA-HOTAIR by binding to specific sites on lncRNA-HOTAIR. We used superparamagnetic iron oxide nanoparticles (SPIONs) to mediate the high expression of microRNA-141 (SPIONs@miR-141) in human amniotic epithelial stem cells (HuAESCs), which was followed by the induction of the differentiation of HuAESCs into dopaminergic neuron-like cells (iDNLCs). qPCR, western blot, immunofluorescence staining and HPLC all suggested that SPION-mediated overexpression of miR-141 could promote an increased expression of brain-derived neurotrophic factor (BDNF), DAT and 5-TH in HuAESC-derived iDNLCs...
February 7, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29402177/in-vitro-modeling-of-leucine-rich-repeat-kinase-2-lrrk2-g2019s-mediated-parkinson-s-disease-pathology
#5
Scott C Vermilyea, Marina Emborg
Leucine-rich repeat kinase 2 (LRRK2) G2019S (glycine to serine) is the most common mutation associated with sporadic and familial Parkinson's disease (PD) with 80% penetrance by age 70. This mutation is found worldwide, with up to 40% of individuals in the North African Arab population carrying the mutation. Induced pluripotent stem cells (iPSCs) derived from fibroblasts of patients carrying the LRRK2 G2019S mutation have been a critical source of cells for generating dopaminergic neurons and studying G2019S-related pathology...
February 5, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29401731/bc-box-motif-mediated-neuronal-differentiation-of-somatic-stem-cells
#6
Hiroshi Kanno, Yuqun Xu, Taykua Miyakawa, Atsuhiko Kubo, Tetsuhiro Higashida, Nahoko Baily Kobayashi, Tetsuhiko Yoshida, Masaru Tanokura
Von Hippel-Lindau tumor suppressor protein (pVHL) functions to induce neuronal differentiation of neural stem/progenitor cells (NSCs) and skin-derived precursors (SKPs). Here we identified a neuronal differentiation domain (NDD) in pVHL. Neuronal differentiation of SKPs was induced by intracellular delivery of a peptide composed of the amino-acid sequences encoded by the NDD. Neuronal differentiation mediated by the NDD was caused by the binding between it and elongin C followed by Janus kinase-2 (JAK2) ubiquitination of JAK2 and inhibition of the JAK2/the signal transducer and activator of transcription-3(STAT)3 pathway...
February 5, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29396183/astrocytes-attenuate-mitochondrial-dysfunctions-in-human-dopaminergic-neurons-derived-from-ipsc
#7
Fang Du, Qing Yu, Allen Chen, Doris Chen, Shirley ShiDu Yan
Astrocytes, the most populous glial cell type in the brain, are critical for regulating the brain microenvironment. In various neurodegenerative diseases, astrocytes determine the progression and outcome of the neuropathological process. We have recently revealed the direct involvement of mitochondrial function in human pluripotent stem cell (hiPSC)-derived dopaminergic (DA) neuronal differentiation. Using the astroglial-neuronal co-culture system, we show here that astrocytes effectively rescue defects in neurogenesis of DA neurons with mitochondrial respiratory chain disruption...
January 26, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29372743/dextran-coated-iron-oxide-nanoparticle-improved-therapeutic-effects-of-human-mesenchymal-stem-cells-in-a-mouse-model-of-parkinson-s-disease
#8
Tsai-Hua Chung, Szu-Chun Hsu, Shu-Hui Wu, Jong-Kai Hsiao, Chih-Peng Lin, Ming Yao, Dong-Ming Huang
Parkinson's disease (PD) is a prevalent neurodegenerative disease characterized by the loss of dopaminergic (DA) neurons. With their migration capacity toward the sites of diseased DA neurons in the PD brain, mesenchymal stem cells (MSCs) have the potential to differentiate to DA neurons for the replacement of damaged neurons and to secrete neurotrophic factors for the protection and regeneration of diseased DA neurons; therefore MSCs show promise for the treatment of PD. In this study, for the first time, we demonstrate that dextran-coated iron oxide nanoparticles (Dex-IO NPs) can improve the therapeutic efficacy of human MSCs (hMSCs) in a mouse model of PD induced by a local injection of 6-hydroxydopamine (6-OHDA)...
January 26, 2018: Nanoscale
https://www.readbyqxmd.com/read/29368696/guggulsterone-releasing-microspheres-direct-the-differentiation-of-human-induced-pluripotent-stem-cells-into-neural-phenotypes
#9
Andrew Agbay, Laura De La Vega, Gillian Nixon, Stephanie Michelle Willerth
Parkinson's disease (PD), a common neurodegenerative disorder, results from the loss of motor function when dopaminergic neurons (DNs) in the brain selectively degenerate. While pluripotent stem cells (PSCs) show promise for generating replacement neurons, current protocols for generating terminally differentiated DNs require a complicated cocktail of factors. Recent work demonstrated that a naturally occurring steroid called guggulsterone effectively differentiated PSCs into DNs, simplifying this process. In this study, we encapsulated guggulsterone into novel poly-ε-caprolactone (PCL)-based microspheres and characterized its release profile over 44 days in vitro, demonstrating we can control its release over time...
January 25, 2018: Biomedical Materials
https://www.readbyqxmd.com/read/29354319/dopaminergic-enhancement-of-cellular-adhesion-in-bone-marrow-derived-mesenchymal-stem-cells-mscs
#10
Si Chen, Bing Bai, Dong Joon Lee, Shannon Diachina, Yina Li, Sing Wai Wong, Zhengyan Wang, Henry C Tseng, Ching-Chang Ko
Dopamine (DA) is a well-known neurotransmitter and critical element in the mussel adhesive protein that has gained increasing attention for its role in cellular growth enhancement in biomaterials, including cellular adhesion improvement. As the mechanism underlying this remains unclear, the objective of this study was to explore the effects of DA on the adhesion properties of bone marrow derived rat mesenchymal stem cells (rMSCs) using an hydroxyapatite gelatin nanocomposite biomaterial and to test whether the effects are mediated through various endogenously expressed DA receptors...
August 2017: Journal of Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29339826/using-intracellular-markers-to-identify-a-novel-set-of-surface-markers-for-live-cell-purification-from-a-heterogeneous-hipsc-culture
#11
Elizabeth J Paik, Alison L O'Neil, Shi-Yan Ng, Chicheng Sun, Lee L Rubin
Human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can provide sources for midbrain dopaminergic (mDA) neural progenitors (NPCs) for cell therapy to treat Parkinson's disease (PD) patients. However, the well-known line-to-cell line variability in the differentiation capacity of individual cell lines needs to be improved for the success of this therapy. To address this issue, we sought to identify mDA NPC specific cell surface markers for fluorescence activated cell sorting (FACS). Through RNA isolation after sorting for NPCs based on staining for cell-specific transcription factors followed by microarray, we identified two positive cell surface markers (CORIN and CD166) and one negative cell surface marker (CXCR4) for mDA NPC sorting...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29338033/intermittent-low-dose-carbon-monoxide-exposure-enhances-survival-and-dopaminergic-differentiation-of-human-neural-stem-cells
#12
Nanna Dreyer-Andersen, Ana Sofia Almeida, Pia Jensen, Morad Kamand, Justyna Okarmus, Tine Rosenberg, Stig Düring Friis, Alberto Martínez Serrano, Morten Blaabjerg, Bjarne Winther Kristensen, Troels Skrydstrup, Jan Bert Gramsbergen, Helena L A Vieira, Morten Meyer
Exploratory studies using human fetal tissue have suggested that intrastriatal transplantation of dopaminergic neurons may become a future treatment for patients with Parkinson's disease. However, the use of human fetal tissue is compromised by ethical, regulatory and practical concerns. Human stem cells constitute an alternative source of cells for transplantation in Parkinson's disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting in both protection and generation of reactive oxygen species...
2018: PloS One
https://www.readbyqxmd.com/read/29321139/bmp-smad-pathway-promotes-neurogenesis-of-midbrain-dopaminergic-neurons-in-vivo-and-in-human-induced-pluripotent-and-neural-stem-cells
#13
V M Jovanovic, A Salti, H Tilleman, K Zega, M M Jukic, H Zou, R H Friedel, N Prakash, S Blaess, F Edenhofer, C Brodski
The embryonic formation of midbrain dopaminergic (mDA) neurons in vivo provides critical guidelines for the in vitro differentiation of mDA neurons from stem cells, currently being developed for Parkinson's disease cell replacement therapy. Bone morphogenetic protein (BMP)/SMAD inhibition is routinely used during early steps of stem cell differentiation protocols, including for the generation of mDA neurons. However, the function of the BMP/SMAD pathway for in vivo specification of mammalian mDA neurons is virtually unknown...
January 10, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29311330/gba1-deficiency-negatively-affects-physiological-%C3%AE-synuclein-tetramers-and-related-multimers
#14
Sangjune Kim, Seung Pil Yun, Saebom Lee, George Essien Umanah, Veera Venkata Ratnam Bandaru, Xiling Yin, Peter Rhee, Senthilkumar S Karuppagounder, Seung-Hwan Kwon, Hojae Lee, Xiaobo Mao, Donghoon Kim, Akhilesh Pandey, Gabsang Lee, Valina L Dawson, Ted M Dawson, Han Seok Ko
Accumulating evidence suggests that α-synuclein (α-syn) occurs physiologically as a helically folded tetramer that resists aggregation. However, the mechanisms underlying the regulation of formation of α-syn tetramers are still mostly unknown. Cellular membrane lipids are thought to play an important role in the regulation of α-syn tetramer formation. Since glucocerebrosidase 1 (GBA1) deficiency contributes to the aggregation of α-syn and leads to changes in neuronal glycosphingolipids (GSLs) including gangliosides, we hypothesized that GBA1 deficiency may affect the formation of α-syn tetramers...
January 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29311261/towards-stem-cell-based-therapies-for-parkinson-s-disease
#15
Malin Parmar
Treating neurodegenerative diseases with cell transplantation has been within reach since the first pioneering clinical trials in which dopamine neuron progenitors from the fetal brain were transplanted to individuals with Parkinson's disease. However, the use of fetal tissue is problematic in terms of low availability and high variability, and it is also associated with ethical concerns that vary between countries. For decades, the field has therefore investigated new scalable source of therapeutic cells from stem cells or via reprogramming...
January 8, 2018: Development
https://www.readbyqxmd.com/read/29285614/the-effects-of-quinine-on-neurophysiological-properties-of-dopaminergic-neurons
#16
Li Zou, Yingchao Xue, Michael Jones, Thomas Heinbockel, Mingyao Ying, Xiping Zhan
Quinine is an antimalarial drug that is toxic to the auditory system by commonly inducing hearing loss and tinnitus, presumably due to its ototoxic effects on disruption of cochlear hair cells and blockade of ion channels of neurons in the auditory system. To a lesser extent, quinine also causes ataxia, tremor, and dystonic reactions. As dopaminergic neurons are implicated to play a role in all of these diseases, we tested the toxicity of quinine on induced dopaminergic (iDA) neurons derived from human pluripotent stem cells (iPSCs) and primary dopaminergic (DA) neurons of substantia nigra from mice brain slices...
December 29, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29234887/ips-cells-in-the-study-of-pd-molecular-pathogenesis
#17
REVIEW
Melanie M Cobb, Abinaya Ravisankar, Gaia Skibinski, Steven Finkbeiner
Parkinson's disease (PD) is the second most common neurodegenerative disease and its pathogenic mechanisms are poorly understood. The majority of PD cases are sporadic but a number of genes are associated with familial PD. Sporadic and familial PD have many molecular and cellular features in common, suggesting some shared pathogenic mechanisms. Induced pluripotent stem cells (iPSCs) have been derived from patients harboring a range of different mutations of PD-associated genes. PD patient-derived iPSCs have been differentiated into relevant cell types, in particular dopaminergic neurons and used as a model to study PD...
December 12, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29217999/prospects-for-modeling-abnormal-neuronal-function-in-schizophrenia-using-human-induced-pluripotent-stem-cells
#18
REVIEW
Iya Prytkova, Kristen J Brennand
Excitatory dopaminergic neurons, inhibitory GABAergic neurons, microglia, and oligodendrocytes have all been implicated in schizophrenia (SZ) network pathology. Still, SZ has been a difficult disorder to study, not only because of the limitations of animal models in capturing the complexity of the human mind, but also because it is greatly polygenic, with high rates of variability across the population. The advent of patient-derived pluripotent stem cells and induced neural and glial cultures has brought hope for modeling the molecular dysfunction underlying SZ pathology in a patient-specific manner...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29217686/synaptic-regulator-%C3%AE-synuclein-in-dopaminergic-fibers-is-essentially-required-for-the-maintenance-of-subependymal-neural-stem-cells
#19
Ana Perez-Villalba, Mª Salomé Sirerol-Piquer, Germán Belenguer, Raúl Soriano-Cantón, Ana Belén Muñoz-Manchado, Javier Villadiego, Diana Alarcón-Arís, Federico N Soria, Benjamin Dehay, Erwan Bezard, Miquel Vila, Analía Bortolozzi, Juan José Toledo-Aral, Francisco Pérez-Sánchez, Isabel Fariñas
Synaptic protein α-synuclein (α-SYN) modulates neurotransmission in a complex and poorly understood manner and aggregates in the cytoplasm of degenerating neurons in Parkinson's disease. Here, we report that α-SYN present in dopaminergic nigral afferents is essential for the normal cycling and maintenance of neural stem cells (NSCs) in the brain subependymal zone of adult male and female mice. We also show that premature senescence of adult NSCs into non-neurogenic astrocytes in mice lacking α-SYN resembles the effects of dopaminergic fiber degeneration resulting from chronic exposure to MPTP or intranigral inoculation of aggregated toxic α-SYN...
December 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29207913/generation-of-dopamine-secreting-cells-from-human-adipose-tissue-derived-stem-cells-in-vitro
#20
Mohammad Hasan Soheilifar, Arash Javeri, Hossein Amini, Masoumeh Fakhr Taha
Several studies have demonstrated the differentiation of human adipose tissue-derived stem cells (hADSCs) to neuronal and glial phenotypes, but directing the fate of these cells toward dopaminergic neurons has not been frequently reported. The aim of the present study was to investigate dopaminergic specification of hADSCs in vitro. ADSCs were isolated from subcutaneous abdominal adipose tissue and were characterized. For dopaminergic differentiation, a cocktail of sonic hedgehog, fibroblast growth factor 8, basic fibroblast growth factor and brain-derived neurotrophic factor were used under a low serum condition...
December 5, 2017: Rejuvenation Research
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