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dopaminergic stem cells

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
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
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
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...
September 27, 2016: Stem Cell Reports
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
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
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
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
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
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
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
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
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
Jun Takahashi
The aim of stem cell therapy for Parkinson's disease (PD) is to reconstruct local synapse formation and/or induce the release of dopamine and cytokines from grafted cells in the putamen. Fetal ventral-midbrain cells reportedly relieve the neurological symptoms of PD patients. However, induced pluripotent stem cells (iPSCs) are expected to provide an alternative donor cell population because of their capacity for self-renewal and pluripotency. A protocol to generate dopaminergic (DA) neurons from iPSCs has been developed, and human ESCs were proven to function in the brains of rat and monkey PD models...
August 2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Tim Kao, Tanya Labonne, Jonathan C Niclis, Ritu Chaurasia, Zerina Lokmic, Elizabeth Qian, Freya F Bruveris, Sara E Howden, Ali Motazedian, Jacqueline V Schiesser, Magdaline Costa, Koula Sourris, Elizabeth Ng, David Anderson, Antonietta Giudice, Peter Farlie, Michael Cheung, Shireen R Lamande, Anthony J Penington, Clare L Parish, Lachlan H Thomson, Arash Rafii, David A Elliott, Andrew G Elefanty, Edouard G Stanley
The ability to reliably express fluorescent reporters or other genes of interest is important for using human pluripotent stem cells (hPSCs) as a platform for investigating cell fates and gene function. We describe a simple expression system, designated GAPTrap (GT), in which reporter genes, including GFP, mCherry, mTagBFP2, luc2, Gluc, and lacZ are inserted into the GAPDH locus in hPSCs. Independent clones harboring variations of the GT vectors expressed remarkably consistent levels of the reporter gene. Differentiation experiments showed that reporter expression was reliably maintained in hematopoietic cells, cardiac mesoderm, definitive endoderm, and ventral midbrain dopaminergic neurons...
September 13, 2016: Stem Cell Reports
Jisook Moon, Sigrid C Schwarz, Hyun-Seob Lee, Jun Mo Kang, Young-Eun Lee, Bona Kim, Mi-Young Sung, Günter Höglinger, Florian Wegner, Jin Su Kim, Hyung-Min Chung, Sung Woon Chang, Kwang Yul Cha, Kwang-Soo Kim, Johannes Schwarz
: : We have developed a good manufacturing practice for long-term cultivation of fetal human midbrain-derived neural progenitor cells. The generation of human dopaminergic neurons may serve as a tool of either restorative cell therapies or cellular models, particularly as a reference for phenotyping region-specific human neural stem cell lines such as human embryonic stem cells and human inducible pluripotent stem cells. We cultivated 3 different midbrain neural progenitor lines at 10, 12, and 14 weeks of gestation for more than a year and characterized them in great detail, as well as in comparison with Lund mesencephalic cells...
September 2, 2016: Stem Cells Translational Medicine
Yan-Hua Li, Jing-Wen Yu, Jian-Yin Xi, Wen-Bo Yu, Jian-Chun Liu, Qing Wang, Li-Juan Song, Ling Feng, Ya-Ping Yan, Guang-Xian Zhang, Bao-Guo Xiao, Cun-Gen Ma
Bone marrow-derived neural stem cells (NSCs) are ideal cells for cellular therapy because of their therapeutic potential for repairing and regenerating damaged neurons. However, the optimization of implanted cells and the improvement of microenvironment in the central nervous system (CNS) are still two critical elements for enhancing therapeutic effect. In the current study, we observed the combined therapeutic effect of NSCs with fasudil in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model and explored the possible cellular and molecular mechanisms...
September 2, 2016: Molecular Neurobiology
Yang Sheng, Emily Filichia, Elizabeth Shick, Kenzie L Preston, Karran A Phillips, Leslie Cooperman, Zhicheng Lin, Paul Tesar, Barry Hoffer, Yu Luo
INTRODUCTION: The dopaminergic (DA) system plays important roles in addiction. However, human DA neurons from drug-dependent subjects were not available for study until recent development in inducible pluripotent stem cells (iPSCs) technology. METHODS: In this study, we produced DA neurons differentiated using iPSCs derived from opioid-dependent and control subjects carrying different 3' VNTR (variable number tandem repeat) polymorphism in the human dopamine transporter (DAT or SLC6A3)...
August 2016: Brain and Behavior
Abbas Aliaghaei, Mossa Gardaneh, Nader Maghsoudi, Parvin Salehinejad, Ehsan Gharib
BACKGROUND/OBJECTIVE: Degeneration of dopaminergic neurons in Parkinson's disease (PD) implies cell replacement using potentially differentiable sources as a promising therapeutic solution. We tested the capacity of conditioned medium from choroid plexus epithelial cells (CPECs-CM) to induce the dopaminergic potential of umbilical cord matrix mesenchymal stem cells (UCMSCs). METHODS: We isolated UCMSCs from human umbilical cord and CPECs from rat brain. Following expansion and characterization, CPECs-CM were collected, tested for expression of various growth factors, and applied to UCMSCs...
August 2016: Archives of Iranian Medicine
Jose A Morales-Garcia, Victor Echeverry-Alzate, Sandra Alonso-Gil, Marina Sanz-SanCristobal, Jose A Lopez-Moreno, Carmen Gil, Ana Martinez, Angel Santos, Ana Perez-Castillo
The phosphodiesterase 7 (PDE7) enzyme is one of the enzymes responsible for controlling intracellular levels of cyclic adenosine 3',5'-monophosphate in the immune and central nervous system. We have previously shown that inhibitors of this enzyme are potent neuroprotective and anti-inflammatory agents. In addition we also demonstrated that PDE7 inhibition induces endogenous neuroregenerative processes towards a dopaminergic phenotype. Here, we show that PDE7 inhibition controls stem cell expansion in the subgranular zone of the dentate gyrus of the hippocampus (SGZ) and the subventricular zone (SVZ) in the adult rat brain...
August 19, 2016: Stem Cells
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