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dopaminergic stem cells

Yutaka Mine, Toshihiko Momiyama, Takuro Hayashi, Takeshi Kawase
Although recent progress in the use of human iPS cell-derived midbrain dopaminergic progenitors is remarkable, alternatives are essential in the strategies of treatment of basal-ganglia-related diseases. Attention has been focused on neural stem cells (NSCs) as one of the possible candidates of donor material for neural transplantation, because of their multipotency and self-renewal characteristics. In the present study, miniature-swine (mini-swine) mesencephalic neuroepithelial stem cells (M-NESCs) of embryonic 17 and 18 days grafted in the parkinsonian rat striatum were assessed immunohistochemically, behaviourally and electrophysiologically to confirm their feasibility for the neural xenografting as a donor material...
June 19, 2018: Neuroscience
Parnit K Bhupal, Kevin A Anderson, Gabrielle P Shall, Jonathan D Lynn, Katrina S Hoolsema, Julien Rossignol, Gary L Dunbar, Michael I Sandstrom
BACKGROUND: Putative treatments derived from in-vivo stem cell transplant derived dopamine (DA) assessed with hemiparkinsonian rats have been assessed via DA-agonist-induced rotations involving imbalanced intra-hemispheric striatal DA receptor stimulation. However, such tests obscure the natural responses of grafts to sensory stimuli, and drug-induced plasticity can modify the circuit being tested. Thus, we propose an alternative testing strategy using a novel water tank swimming apparatus...
June 17, 2018: Journal of Neuroscience Methods
Ginetta Collo, Laura Cavalleri, Michele Zoli, Uwe Maskos, Emiliangelo Ratti, Emilio Merlo Pich
Midbrain dopamine (DA) neurons are considered a critical substrate for the reinforcing and sensitizing effects of nicotine and tobacco dependence. While the role of the α4 and β2 subunit containing nicotinic acetylcholine receptors (α4β2∗ nAChRs) in mediating nicotine effects on DA release and DA neuron activity has been widely explored, less information is available on their role in the morphological adaptation of the DA system to nicotine, eventually leading to dysfunctional behaviors observed in nicotine dependence...
2018: Frontiers in Pharmacology
Yu-Kai Wang, Wan-Wan Zhu, Meng-Hua Wu, Yi-Hui Wu, Zheng-Xin Liu, Ling-Min Liang, Chao Sheng, Jie Hao, Liu Wang, Wei Li, Qi Zhou, Bao-Yang Hu
Clinical application of stem cell derivatives requires clinical-grade cells and sufficient preclinical proof of safety and efficacy, preferably in primates. We previously successfully established a clinical-grade human parthenogenetic embryonic stem cell (hPESC) line, but the suitability of its subtype-specific progenies for therapy is not clear. Here, we compared the function of clinical-grade hPESC-derived midbrain dopaminergic (DA) neurons in two canonical protocols in a primate Parkinson's disease (PD) model...
June 7, 2018: Stem Cell Reports
Daniel Little, Christin Luft, Olukunbi Mosaku, Maëlle Lorvellec, Zhi Yao, Sébastien Paillusson, Janos Kriston-Vizi, Sonia Gandhi, Andrey Y Abramov, Robin Ketteler, Michael J Devine, Paul Gissen
Mitochondrial dysfunction is implicated in many neurodegenerative diseases including Parkinson's disease (PD). Induced pluripotent stem cells (iPSCs) provide a unique cell model for studying neurological diseases. We have established a high-content assay that can simultaneously measure mitochondrial function, morphology and cell viability in iPSC-derived dopaminergic neurons. iPSCs from PD patients with mutations in SNCA and unaffected controls were differentiated into dopaminergic neurons, seeded in 384-well plates and stained with the mitochondrial membrane potential dependent dye TMRM, alongside Hoechst-33342 and Calcein-AM...
June 13, 2018: Scientific Reports
David C Schöndorf, Dina Ivanyuk, Pascale Baden, Alvaro Sanchez-Martinez, Silvia De Cicco, Cong Yu, Ivana Giunta, Lukas K Schwarz, Gabriele Di Napoli, Vasiliki Panagiotakopoulou, Sigrun Nestel, Marcus Keatinge, Jan Pruszak, Oliver Bandmann, Bernd Heimrich, Thomas Gasser, Alexander J Whitworth, Michela Deleidi
While mitochondrial dysfunction is emerging as key in Parkinson's disease (PD), a central question remains whether mitochondria are actual disease drivers and whether boosting mitochondrial biogenesis and function ameliorates pathology. We address these questions using patient-derived induced pluripotent stem cells and Drosophila models of GBA-related PD (GBA-PD), the most common PD genetic risk. Patient neurons display stress responses, mitochondrial demise, and changes in NAD+ metabolism. NAD+ precursors have been proposed to ameliorate age-related metabolic decline and disease...
June 5, 2018: Cell Reports
Han Wool Kim, Hyun-Seob Lee, Jun Mo Kang, Sang-Hun Bae, Chul Kim, Sang-Hun Lee, Johannes Schwarz, Gi Jin Kim, Jin-Su Kim, Dong Hyun Cha, Joopyung Kim, Sung Woon Chang, Tae Hee Lee, Jisook Moon
Parkinson's disease (PD) is the second most common age-related neurodegenerative disease in the elderly and the patients suffer from uncontrolled movement disorders due to loss of dopaminergic (DA) neurons on substantia nigra pars compacta (SNpc). We previously reported that transplantation of human fetal midbrain-derived neural precursor cells restored the functional deficits of a 6-hydroxy dopamine (6-OHDA)-treated rodent model of PD but its low viability and ethical issues still remain to be solved. Albeit immune privilege and neural differentiation potentials suggest mesenchymal stem cells (MSCs) from various tissues including human placenta MSCs (hpMSCs) for an alternative source, our understanding of their therapeutic mechanisms is still limited...
January 1, 2018: Cell Transplantation
John P Wise, Charles G Price, Joseph A Amaro, Jason R Cannon
The motor features of Parkinson's disease (PD) primarily result from a lesion to the nigrostriatal dopamine system. Numerous non-motor symptoms occur in PD, many of which are postulated to stem from pathology outside of the nigrostriatal dopamine system. Perturbations to protein trafficking, disruption of mitochondrial integrity, and impaired autophagy have repeatedly been implicated in dopaminergic neuron cell death. Previously, we demonstrated that multiple markers of autophagy are disrupted in a rotenone model of PD, with alterations occurring prior to an overt lesion to the nigrostriatal dopamine system...
2018: Frontiers in Neuroscience
Mohammed Abdel-Rahman, Rania A Galhom, Wael Amin Nasr El-Din, Mona H Mohammed Ali, Alaa El-Din Saad Abdel-Hamid
BACKGROUND: Olfactory stem cells (OSCs) are found in the olfactory mucosa and olfactory bulb and have the capacity to proliferate and differentiate along multiple tissue lineages. Rotenone; widely used insecticide has a neurodegenerative effect on the dopaminergic cells of substantia nigra (SN) of midbrain producing Parkinsonism. The aim of this study is to isolate rat OSCs from olfactory mucosa and olfactory bulb, culture these OSCs in suitable medium to allow for their proliferation to be used in the treatment of Parkinsonism induced by rotenone...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Gincy George, Sachidanand Singh, Sowmya Bekshe Lokappa, Jobin Varkey
Parkinson's disease (PD) is a neurodegenerative disorder involving progressive deterioration of dopaminergic neurons. Although few genetic markers for familial PD are known, the etiology of sporadic PD remains poorly understood. Microarray data was analysed for induced pluripotent stem cells (iPSCs) derived from PD patients and mature neuronal cells (mDA) differentiated from these iPSCs. Combining expression and semantic similarity, a highly-correlated PD interactome was constructed that included interactions of established Parkinson's disease marker genes...
May 28, 2018: Genomics
Ali Fathi, Mehdi Mirzaei, Banafsheh Dolatyar, Mehdi Sharifitabar, Mahnaz Bayat, Ebrahim Shahbazi, Jaesuk Lee, Mohammad Javan, Su-Chun Zhang, Vivek Gupta, Bonghee Lee, Paul A Haynes, Hossein Baharvand, Ghasem Hosseini Salekdeh
Despite the progress in safety and efficacy of cell replacement therapy with pluripotent stem cells (PSCs), the presence of residual undifferentiated stem cells or proliferating neural progenitor cells (NPCs) with rostral identity remains a major challenge. Here we report the generation of a LIM homeobox transcription factor 1 alpha (LMX1A) knock-in GFP reporter human embryonic stem cell (hESC) line that marks the early dopaminergic progenitors during neural differentiation to find reliable membrane protein markers for isolation of midbrain dopaminergic neurons...
May 29, 2018: Molecular & Cellular Proteomics: MCP
Malihe Nakhaeifard, Maryam Haji Ghasem Kashani, Iran Goudarzi, Arezou Rezaei
Objective: Adipose derived stem cells (ASCs) secrete numerous neurotrophic factors and cytokines in conditioned medium (CM), which protect neurons by its antioxidative and trophic effects. This research assesses the neuroprotective effect of ASCCM on neurotrophins genes expressions and tyrosine hydroxylase positive (TH+ ) cell density in male Wistar rats lesioned by 6-hydroxydopamine (6-OHDA). Materials and Methods: In this experimental study, the groups consisted of lesioned and sham rats with unilateral injections of 20 μg of 6-OHDA neurotoxin and phosphate buffered saline (PBS) into the striatum, respectively...
October 2018: Cell Journal
Goun Je, Subhrangshu Guhathakurta, Seung Pil Yun, Han Seok Ko, Yoon-Seong Kim
Alpha-synuclein (α-SYN) is one of the key contributors in Parkinson's disease (PD) pathogenesis. Despite the fact that increased α-SYN levels are considered one of the key contributors in developing PD, the molecular mechanisms underlying the regulation of α-SYN still needs to be elucidated. Since the 3' untranslated regions (3'UTRs) of messenger RNAs (mRNAs) have important roles in translation, localization, and stability of mRNAs through RNA binding proteins (RBPs) and microRNAs (miRNAs), it is important to identify the exact length of 3'UTRs of transcripts in order to understand the precise regulation of gene expression...
May 25, 2018: Molecular Brain
Mahendra S Rao, Ying Pei, Thelma Y Garcia, Shereen Chew, Toshiharu Kasai, Tomoko Hisai, Hideki Taniguchi, Takanori Takebe, Deepak A Lamba, Xianmin Zeng
We have previously reported the generation of a current Good Manufacture Practice (cGMP)-compliant induced pluripotent stem cell (iPSC) line for clinical applications. Here we show that multiple cellular products currently being considered for therapy can be generated from a single master cell bank of this or any other clinically compliant iPSC line METHODS: Using a stock at passage 20 prepared from the cGMP-compliant working cell bank (WCB), we tested differentiation into therapeutically relevant cell types of the three germ layers using standardized but generic protocols...
May 21, 2018: Cytotherapy
Laura A Struzyna, Kevin D Browne, Zachary D Brodnik, Justin C Burrell, James P Harris, H Isaac Chen, John A Wolf, Kate V Panzer, James Lim, John E Duda, Rodrigo A España, D Kacy Cullen
The classic motor deficits of Parkinson's disease are caused by degeneration of dopaminergic neurons in the substantia nigra pars compacta, resulting in the loss of their long-distance axonal projections that modulate the striatum. Current treatments only minimize the symptoms of this disconnection as there is no approach capable of replacing the nigrostriatal pathway. We are applying micro-tissue engineering techniques to create living, implantable constructs that mimic the architecture and function of the nigrostriatal pathway...
May 15, 2018: Journal of Tissue Engineering and Regenerative Medicine
Kang Chi, Ru-Huei Fu, Yu-Chuen Huang, Shih-Yin Chen, Ching-Ju Hsu, Shinn-Zong Lin, Chi-Tang Tu, Li-Hsun Chang, Ping-An Wu, Shih-Ping Liu
Parkinson's disease (PD) causes motor dysfunction and dopaminergic cell death. Drug treatments can effectively reduce symptoms but often cause unwanted side effects. Stem cell therapies using cell replacement or indirect beneficial secretomes have recently emerged as potential therapeutic strategies. Although various types of stem cells have been proposed as possible candidates, adipose-derived stem cells (ADSCs) are easily obtainable, more abundant, less ethically disputed, and able to differentiate into multiple cell lineages...
January 1, 2018: Cell Transplantation
Kyle Denton, Yongchao Mou, Chong-Chong Xu, Dhruvi Shah, Jaerak Chang, Craig Blackstone, Xue-Jun Li
Mechanisms by which long corticospinal axons degenerate in hereditary spastic paraplegia (HSP) are largely unknown. Here, we have generated induced pluripotent stem cells (iPSCs) from patients with two autosomal recessive forms of HSP, SPG15 and SPG48, which are caused by mutations in the ZFYVE26 and AP5Z1 genes encoding proteins in the same complex, the spastizin and AP5Z1 proteins, respectively. In patient iPSC-derived telencephalic glutamatergic and midbrain dopaminergic neurons, neurite number, length and branching are significantly reduced, recapitulating disease-specific phenotypes...
May 2, 2018: Human Molecular Genetics
Morgan G Stykel, Kayla Humphries, Mathew P Kirby, Chris Czaniecki, Tinya Wang, Tammy Ryan, Vladimir Bamm, Scott D Ryan
Neuronal loss in Parkinson's disease (PD) is associated with aberrant mitochondrial function in dopaminergic (DA) neurons of the substantia nigra pars compacta. An association has been reported between PD onset and exposure to mitochondrial toxins, including the agrochemicals paraquat (PQ), maneb (MB), and rotenone (Rot). Here, with the use of a patient-derived stem cell model of PD, allowing comparison of DA neurons harboring a mutation in the α-synuclein (α-syn) gene ( SNCA-A53T) against isogenic, mutation-corrected controls, we describe a novel mechanism whereby NO, generated from SNCA-A53T mutant neurons exposed to Rot or PQ/MB, inhibits anterograde mitochondrial transport through nitration of α-tubulin (α-Tub)...
April 24, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Jacopo Zasso, Mastad Ahmed, Alessandro Cutarelli, Luciano Conti
Converging evidence suggest that levels of alpha-synuclein (aSyn) expression play a critical role in Parkinson's disease (PD). Several mutations of the SNCA gene, encoding for aSyn have been associated to either the familial or the sporadic forms of PD. Nonetheless, the mechanism underlying wild-type aSyn-mediated neurotoxicity in neuronal cells as well as its specific driving role in PD pathogenesis has yet to be fully clarified. In this view, the development of proper in vitro cellular systems is a crucial step...
May 29, 2018: Stem Cells and Development
Ji Young Kim, Jae Souk Lee, Hyun Sub Hwang, Dongjin R Lee, Chul-Yong Park, Sung Jun Jung, Young Rang You, Dae-Sung Kim, Dong-Wook Kim
The canonical Wnt signal pathway plays a pivotal role in anteroposterior patterning and midbrain specification during early neurogenesis. Activating Wnt signal has been a strategy for differentiating human pluripotent stem cells (PSCs) into midbrain dopaminergic (DA) neurons; however, the underlying molecular mechanism(s) of how the Wnt signal drives posterior fate remained unclear. In this study, we found that activating the canonical Wnt signal significantly upregulated the expression of EN1, a midbrain-specific marker, in a fibroblast growth factor signal-dependent manner in human PSC-derived neural precursor cells (NPCs)...
April 13, 2018: Experimental & Molecular Medicine
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