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induced pluripotent stem cell microglia

Attila Szabo, Attila Kovacs, Jordi Riba, Srdjan Djurovic, Eva Rajnavolgyi, Ede Frecska
N,N-dimethyltryptamine (DMT) is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R), an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER) and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins...
2016: Frontiers in Neuroscience
Julien Muffat, Yun Li, Bingbing Yuan, Maisam Mitalipova, Attya Omer, Sean Corcoran, Grisilda Bakiasi, Li-Huei Tsai, Patrick Aubourg, Richard M Ransohoff, Rudolf Jaenisch
Microglia, the only lifelong resident immune cells of the central nervous system (CNS), are highly specialized macrophages that have been recognized to have a crucial role in neurodegenerative diseases such as Alzheimer's, Parkinson's and adrenoleukodystrophy (ALD). However, in contrast to other cell types of the human CNS, bona fide microglia have not yet been derived from cultured human pluripotent stem cells. Here we establish a robust and efficient protocol for the rapid production of microglia-like cells from human (h) embryonic stem (ES) and induced pluripotent stem (iPS) cells that uses defined serum-free culture conditions...
September 26, 2016: Nature Medicine
Rachelle Balez, Nicole Steiner, Martin Engel, Sonia Sanz Muñoz, Jeremy Stephen Lum, Yizhen Wu, Dadong Wang, Pascal Vallotton, Perminder Sachdev, Michael O'Connor, Kuldip Sidhu, Gerald Münch, Lezanne Ooi
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases, yet current therapeutic treatments are inadequate due to a complex disease pathogenesis. The plant polyphenol apigenin has been shown to have anti-inflammatory and neuroprotective properties in a number of cell and animal models; however a comprehensive assessment has not been performed in a human model of AD. Here we have used a human induced pluripotent stem cell (iPSC) model of familial and sporadic AD, in addition to healthy controls, to assess the neuroprotective activity of apigenin...
2016: Scientific Reports
Katrin I Andreasson, Adam D Bachstetter, Marco Colonna, Florent Ginhoux, Clive Holmes, Bruce Lamb, Gary Landreth, Daniel C Lee, Donovan Low, Marina A Lynch, Alon Monsonego, M Kerry O'Banion, Milos Pekny, Till Puschmann, Niva Russek-Blum, Leslie A Sandusky, Maj-Linda B Selenica, Kazuyuki Takata, Jessica Teeling, Terrence Town, Linda J Van Eldik
Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7-9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance...
September 2016: Journal of Neurochemistry
Monika Myszczynska, Laura Ferraiuolo
Amyotrophic Lateral Sclerosis (ALS) is a complex multifactorial disorder, characterized by motor neuron loss with involvement of several other cell types, including astrocytes, oligodendrocytes and microglia. Studies in vivo and in in vitro models have highlighted that the contribution of non-neuronal cells to the disease is a primary event and ALS pathogenesis is driven by both cell-autonomous and non-cell autonomous mechanisms. The advancements in genetics and in vitro modeling of the past 10 years have dramatically changed the way we investigate the pathogenic mechanisms involved in ALS...
March 2016: Brain Pathology
Sarah E Sullivan, Tracy L Young-Pearse
The ability to accurately and systematically evaluate the cellular mechanisms underlying human neurodegenerative disorders such as Alzheimer׳s disease (AD) should lead to advancements in therapeutics. Recent developments in human induced pluripotent stem cells (iPSCs) have afforded the opportunity to use human neurons and glia to study cellular changes involved in neurological diseases. iPSCs have the potential to be differentiated into AD-relevant cell types, including forebrain neurons, astrocytes, and microglia...
October 13, 2015: Brain Research
Bikun Xian, Bing Huang
Stem cell transplantation is a potential curative treatment for degenerative diseases of the retina. Among cell injection sites, the subretinal space (SRS) is particularly advantageous as it is maintained as an immune privileged site by the retinal pigment epithelium (RPE) layer. Thus, the success of subretinal transplantation depends on maintenance of RPE integrity. Moreover, both embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs) have negligible immunogenicity and in fact are immunosuppressive...
2015: Stem Cell Research & Therapy
Jie Qin, Xun Ma, Haiyun Qi, Bo Song, Yanlin Wang, Xuejun Wen, Qing Mei Wang, Shilei Sun, Yusheng Li, Rui Zhang, Xinjing Liu, Haiman Hou, Guangming Gong, Yuming Xu
BACKGROUND: Little is known about the effects of induced pluripotent stem cell (iPSC) treatment on acute cerebral inflammation and injuries after intracerebral hemorrhage (ICH), though they have shown promising therapeutic potentials in ischemic stoke. METHODS: An ICH model was established by stereotactic injection of collagenase VII into the left striatum of male Sprague-Dawley (SD) rats. Six hours later, ICH rats were randomly divided into two groups and received intracerebrally 10 μl of PBS with or without 1 × 10(6) of iPSCs...
2015: PloS One
Fabien G Lafaille, Michael J Ciancanelli, Lorenz Studer, Gregory Smith, Luigi Notarangelo, Jean-Laurent Casanova, Shen-Ying Zhang
Herpes simplex virus 1 (HSV-1) is a common virus that can rarely invade the human central nervous system (CNS), causing devastating encephalitis. The permissiveness to HSV-1 of the various relevant cell types of the CNS, neurons, astrocytes, oligodendrocytes, and microglia cells, as well as their response to viral infection, has been extensively studied in humans and other animals. Nevertheless, human CNS cell-based models of anti-HSV-1 immunity are of particular importance, as responses to any given neurotropic virus may differ between humans and other animals...
2015: Frontiers in Immunology
Mariusz Ratajczak, Jolanta Kucharska-Mazur, Jerzy Samochowiec
The expanding field of stem cell research is now beginning to help with the problems of modern psychiatry. On the one hand, induced pluripotent stem cells (iPSCs) can now be used to generate neural cell lines from patients suffering from psychiatric disorders, which can then serve as models for studying changes in gene expression pattern involved in the pathogenesis of these diseases. These artificially generated neural cells are also employed in studying the efficacy of newly developed antipsychotic treatments...
November 2014: Psychiatria Polska
Go Itakura, Yoshiomi Kobayashi, Soraya Nishimura, Hiroki Iwai, Morito Takano, Akio Iwanami, Yoshiaki Toyama, Hideyuki Okano, Masaya Nakamura
Our previous work reported functional recovery after transplantation of mouse and human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) into rodent models of spinal cord injury (SCI). Although hiPSC-NS/PCs proved useful for the treatment of SCI, the tumorigenicity of the transplanted cells must be resolved before they can be used in clinical applications. The current study sought to determine the feasibility of ablation of the tumors formed after hiPSC-NS/PC transplantation through immunoregulation...
2015: PloS One
Janice A Maloney, Travis Bainbridge, Amy Gustafson, Shuo Zhang, Roxanne Kyauk, Pascal Steiner, Marcel van der Brug, Yichin Liu, James A Ernst, Ryan J Watts, Jasvinder K Atwal
Pathogenic mutations in the amyloid precursor protein (APP) gene have been described as causing early onset familial Alzheimer disease (AD). We recently identified a rare APP variant encoding an alanine-to-threonine substitution at residue 673 (A673T) that confers protection against development of AD (Jonsson, T., Atwal, J. K., Steinberg, S., Snaedal, J., Jonsson, P. V., Bjornsson, S., Stefansson, H., Sulem, P., Gudbjartsson, D., Maloney, J., Hoyte, K., Gustafson, A., Liu, Y., Lu, Y., Bhangale, T., Graham, R...
November 7, 2014: Journal of Biological Chemistry
Jemal Tatarishvili, Koichi Oki, Emanuela Monni, Philipp Koch, Tamar Memanishvili, Ana-Maria Buga, Vivek Verma, Aurel Popa-Wagner, Oliver Brüstle, Olle Lindvall, Zaal Kokaia
PURPOSE: Induced pluripotent stem cells (iPSCs) improve behavior and form neurons after implantation into the stroke-injured adult rodent brain. How the aged brain responds to grafted iPSCs is unknown. We determined survival and differentiation of grafted human fibroblast-derived iPSCs and their ability to improve recovery in aged rats after stroke. METHODS: Twenty-four months old rats were subjected to 30 min distal middle cerebral artery occlusion causing neocortical damage...
2014: Restorative Neurology and Neuroscience
Seong-Wook Yun, Nam-Young Kang, Sung-Jin Park, Hyung-Ho Ha, Yun Kyung Kim, Jun-Seok Lee, Young-Tae Chang
A cell is the smallest functional unit of life. All forms of life rely on cellular processes to maintain normal functions, and changes in cell function induced by metabolic disturbances, physicochemical damage, infection, or abnormal gene expression may cause disease. To understand basic biology and to develop therapeutics for diseases, researchers need to study live cells. Along with advances in fluorescence microscopy and in vitro cell culture, live-cell imaging has become an essential tool in modern biology for the study of molecular and cellular events...
April 15, 2014: Accounts of Chemical Research
Marcus Karlstetter, Caroline Nothdurfter, Alexander Aslanidis, Katharina Moeller, Felicitas Horn, Rebecca Scholz, Harald Neumann, Bernhard H F Weber, Rainer Rupprecht, Thomas Langmann
BACKGROUND: The translocator protein (18 kDa) (TSPO) is a mitochondrial protein expressed on reactive glial cells and a biomarker for gliosis in the brain. TSPO ligands have been shown to reduce neuroinflammation in several mouse models of neurodegeneration. Here, we analyzed TSPO expression in mouse and human retinal microglia and studied the effects of the TSPO ligand XBD173 on microglial functions. METHODS: TSPO protein analyses were performed in retinoschisin-deficient mouse retinas and human retinas...
2014: Journal of Neuroinflammation
Asuka Morizane, Daisuke Doi, Tetsuhiro Kikuchi, Keisuke Okita, Akitsu Hotta, Toshiyuki Kawasaki, Takuya Hayashi, Hirotaka Onoe, Takashi Shiina, Shinya Yamanaka, Jun Takahashi
Induced pluripotent stem cells (iPSCs) provide the potential for autologous transplantation using cells derived from a patient's own cells. However, the immunogenicity of iPSCs or their derivatives has been a matter of controversy, and up to now there has been no direct comparison of autologous and allogeneic transplantation in the brains of humans or nonhuman primates. Here, using nonhuman primates, we found that the autologous transplantation of iPSC-derived neurons elicited only a minimal immune response in the brain...
2013: Stem Cell Reports
Zhihui Duan, Congmin Ma, Yuezhen Han, Yan Li, Haitao Zhou
Nanog, a unique homeobox transcription factor, maintains self-renewal and pluripotency of embryonic stem cells by binding to nuclear factor κB proteins in order to inhibit their transcriptional and prodifferentiation activities. We previously reported that Nanog attenuated inflammatory responses in rat primary microglia cells stimulated by lipopolysaccharide. However, the effects of Nanog on another microglia cell type, BV-2 cells, are still unknown. In this study, we investigated whether Nanog attenuated inflammatory responses in lipopolysaccharide-stimulated BV-2 cells and found that Nanog significantly decreased the release of nitric oxide and the expression of inducible nitric oxide synthase at the mRNA and protein levels...
September 11, 2013: Neuroreport
Yoshiomi Kobayashi, Yohei Okada, Go Itakura, Hiroki Iwai, Soraya Nishimura, Akimasa Yasuda, Satoshi Nori, Keigo Hikishima, Tsunehiko Konomi, Kanehiro Fujiyoshi, Osahiko Tsuji, Yoshiaki Toyama, Shinya Yamanaka, Masaya Nakamura, Hideyuki Okano
Murine and human iPSC-NS/PCs (induced pluripotent stem cell-derived neural stem/progenitor cells) promote functional recovery following transplantation into the injured spinal cord in rodents. However, for clinical applicability, it is critical to obtain proof of the concept regarding the efficacy of grafted human iPSC-NS/PCs (hiPSC-NS/PCs) for the repair of spinal cord injury (SCI) in a non-human primate model. This study used a pre-evaluated "safe" hiPSC-NS/PC clone and an adult common marmoset (Callithrix jacchus) model of contusive SCI...
2012: PloS One
Holger Braun, Anja Günther-Kern, Klaus Reymann, Brigitte Onteniente
We tested the neuronal differentiation of human iPS-cells under in vitro conditions. For this purpose we pre-differentiated human (h) iPS-cells into neural stem cells and co-cultivated them with a cortical primary culture from embryonic rats. After 2 days of co-cultivation a certain number of hiPS-cells exhibited a clear neuronal morphology combined with expression of betaIII-tubulin and doublecortin. In addition, we found hiPS-cells without neuronal differentiation and cells already expressing betaIII-tubulin but not having yet distinctive axonal and dendritic processes...
2012: Acta Neurobiologiae Experimentalis
Sandra Almeida, Zhijun Zhang, Giovanni Coppola, Wenjie Mao, Kensuke Futai, Anna Karydas, Michael D Geschwind, M Carmela Tartaglia, Fuying Gao, Davide Gianni, Miguel Sena-Esteves, Daniel H Geschwind, Bruce L Miller, Robert V Farese, Fen-Biao Gao
The pathogenic mechanisms of frontotemporal dementia (FTD) remain poorly understood. Here we generated multiple induced pluripotent stem cell lines from a control subject, a patient with sporadic FTD, and an FTD patient with a novel heterozygous GRN mutation (progranulin [PGRN] S116X). In neurons and microglia differentiated from PGRN S116X induced pluripotent stem cells, the levels of intracellular and secreted PGRN were reduced, establishing patient-specific cellular models of PGRN haploinsufficiency. Through a systematic screen of inducers of cellular stress, we found that PGRN S116X neurons, but not sporadic FTD neurons, exhibited increased sensitivity to staurosporine and other kinase inhibitors...
October 25, 2012: Cell Reports
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