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https://www.readbyqxmd.com/read/29334630/generation-of-an-integration-free-induced-pluripotent-stem-cell-line-csc-43j-from-a-patient-with-sporadic-parkinson-s-disease
#1
Ana Marote, Yuriy Pomeshchik, Stefano Goldwurm, Anna Collin, Nuno J Lamas, Luísa Pinto, António J Salgado, Laurent Roybon
An induced pluripotent stem cell (iPSC) line was generated from a 36-year-old patient with sporadic Parkinson's disease (PD). Skin fibroblasts were reprogrammed using the non-integrating Sendai virus technology to deliver OCT3/4, SOX2, c-MYC and KLF4 factors. The generated cell line (CSC-43) exhibits expression of common pluripotency markers, in vitro differentiation into three germ layers and normal karyotype. This iPSC line can be used to study the mechanisms underlying the development of PD.
January 4, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29334629/generation-of-a-human-induced-pluripotent-stem-cell-line-csc-42-from-a-patient-with-sporadic-form-of-parkinson-s-disease
#2
Ekaterina Savchenko, Ana Marote, Kaspar Russ, Anna Collin, Stefano Goldwurm, Laurent Roybon, Yuriy Pomeshchik
Skin fibroblasts were collected from a 44-year-old patient with sporadic case of Parkinson's disease (PD). The non-integrating Sendai virus vector encoding OCT3/4, SOX2, c-MYC and KLF4 was used to reprogram fibroblasts into induced pluripotent stem cells (iPSCs). Generated iPSCs had normal karyotypes, expressed common stem cell markers, and were capable of differentiating into all three germ layers. Generated line could be used for PD modeling to understand the mechanisms that influence the disorder.
January 4, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29334628/production-and-characterization-of-human-induced-pluripotent-stem-cells-ipscs-from-joubert-syndrome-cssi001-a-2850
#3
Jessica Rosati, Filomena Altieri, Silvia Tardivo, Elisa Maria Turco, Marina Goldoni, Iolanda Spasari, Daniela Ferrari, Laura Bernardini, Giuseppe Lamorte, Enza Maria Valente, Angelo Luigi Vescovi
Joubert Syndrome (JS) is a rare autosomal recessive or X-linked condition characterized by a peculiar cerebellar malformation, known as the molar tooth sign (MTS), associated with other neurological phenotypes and multiorgan involvement. JS is a ciliopathy, a spectrum of disorders whose causative genes encode proteins involved in the primary cilium apparatus. In order to elucidate ciliopathy-associated molecular mechanisms, human induced pluripotent stem cells (hiPSCs) were derived from a patient affected by JS carrying a homozygous missense mutation in the AHI1 gene (p...
January 9, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29334242/development-and-disease-in-a-dish-the-epigenetics-of-neurodevelopmental-disorders
#4
Emily Ma Lewis, Kristen L Kroll
Human neurodevelopmental disorders (NDDs) involve mutations in hundreds of individual genes, with over-representation in genes encoding proteins that alter chromatin structure to modulate gene expression. Here, we highlight efforts to model these NDDs through in vitro differentiation of patient-specific induced pluripotent stem cells into neurons. We discuss how epigenetic regulation controls normal cortical development, how mutations in several classes of epigenetic regulators contribute to NDDs, and approaches for modeling cortical development and function using both directed differentiation and formation of cerebral organoids...
January 15, 2018: Epigenomics
https://www.readbyqxmd.com/read/29333086/ethical-and-safety-issues-of-stem-cell-based-therapy
#5
REVIEW
Vladislav Volarevic, Bojana Simovic Markovic, Marina Gazdic, Ana Volarevic, Nemanja Jovicic, Nebojsa Arsenijevic, Lyle Armstrong, Valentin Djonov, Majlinda Lako, Miodrag Stojkovic
Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune and genetic disorders. However, clinical application of stem cells raises numerous ethical and safety concerns. In this review, we provide an overview of the most important ethical issues in stem cell therapy, as a contribution to the controversial debate about their clinical usage in regenerative and transplantation medicine. We describe ethical challenges regarding human embryonic stem cell (hESC) research, emphasizing that ethical dilemma involving the destruction of a human embryo is a major factor that may have limited the development of hESC-based clinical therapies...
2018: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29331938/generation-of-a-human-induced-pluripotent-stem-cell-line-csc-40-from-a-parkinson-s-disease-patient-with-a-pink1-p-q456x-mutation
#6
Kaspar Russ, Ana Marote, Ekaterina Savchenko, Anna Collin, Stefano Goldwurm, Yuriy Pomeshchik, Laurent Roybon
Parkinson's disease (PD) is a neurodegenerative disease with unknown etiology. Here we show the generation of an induced pluripotent stem cell (iPSC) line, named CSC-40, from dermal fibroblasts obtained from a 59-year-old male patient with a homozygous p.Q456X mutation in the PTEN-induced putative kinase 1 (PINK/PARK6) gene and a confirmed diagnosis of PD, which could be used to model familial PD. A non-integrating Sendai virus-based delivery of the reprogramming factors OCT3/4, SOX2, c-MYC and KLF4 was employed...
January 4, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29330434/targeting-melanoma-stem-cells-with-the-vitamin-e-derivative-%C3%AE-tocotrienol
#7
Monica Marzagalli, Roberta Manuela Moretti, Elio Messi, Marina Montagnani Marelli, Fabrizio Fontana, Alessia Anastasia, Maria Rosa Bani, Giangiacomo Beretta, Patrizia Limonta
The prognosis of metastatic melanoma is very poor, due to the development of drug resistance. Cancer stem cells (CSCs) may play a crucial role in this mechanism, contributing to disease relapse. We first characterized CSCs in melanoma cell lines. We observed that A375 (but not BLM) cells are able to form melanospheres and show CSCs traits: expression of the pluripotency markers SOX2 and KLF4, higher invasiveness and tumor formation capability in vivo with respect to parental adherent cells. We also showed that a subpopulation of autofluorescent cells expressing the ABCG2 stem cell marker is present in the A375 spheroid culture...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330131/response-of-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-to-several-pharmacological-agents-when-intrinsic-syncytial-pacing-is-overcome-by-acute-external-stimulation
#8
Haoyu Zeng, Bharathi Balasubramanian, Armando Lagrutta, Frederick Sannajust
We challenged human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) syncytia, mainly, CDI iCells with several classes of well-characterized pharmacological agents (including hERG blocker, Nav1.5 blocker, Cav1.2 blocker and opener, β-adrenergic agonist, and If blocker) under pacing conditions, utilizing the Cardio-ECR instrument, a non-invasive platform featuring simultaneous and continuous measurement of synchronized beating rate and contractility (both signals were acquired simultaneously and well aligned) ...
January 9, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29328972/establishment-of-tusmi003-a-an-induced-pluripotent-stem-cell-ipsc-line-from-a-62-year-old-chinese-han-patient-with-alzheimer-s-disease-with-apoe3-4-genetic-background
#9
Ying Wang, Hongxiang Yu, Yue Zhang, Jing Zhang, Keni Chen, Heng Sun, Shulin Meng, Gang Li, Ying Lei, Jian Zhao
A 62-year old Chinese Han Alzheimer's disease (AD) female patient with ApoE3/4 genetic background donated her Peripheral blood mononuclear cells (PBMC). The non-integrating episomal vector system was used to reprogrammed PBMCs with the human OKSM transcription factors. The pluripotency of transgene-free iPSCs was confirmed by immunocytochemistry for pluripotency markers and by the ability of the iPSCs to differentiate spontaneously into 3 germ layers in vitro. In addition, the iPSC line displayed a normal karyotype...
January 4, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29328449/bioinformatics-analysis-to-screen-key-genes-implicated-in-the-differentiation-of-induced-pluripotent-stem-cells-to-hepatocytes
#10
Rui Lin, Yufeng Wang, Kun Ji, Zhongyan Liu, Shuai Xiao, Dehua Zhou, Quanning Chen, Baomin Shi
Due to the lack of potential organs, hepatocellular transplantation has been considered for treating end-stage liver disease. Induced pluripotent stem cells (iPSCs) are reverted from somatic cells and are able to differentiate into hepatocytes. The present study aimed to investigate the mechanisms underlying iPSC differentiation to hepatocytes. GSE66076 was downloaded from the Gene Expression Omnibus; this database includes data from 3 undifferentiated (T0), 3 definitive endoderm (T5), and 3 early hepatocyte (T24) samples across hepatic‑directed differentiation of iPSCs...
January 5, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29327674/insoluble-microenvironment-facilitating-the-generation-and-maintenance-of-pluripotency
#11
Xiaofang Chen, Jiaqi Li, Yan Huang, Peng Liu, Yubo Fan
Induced pluripotent stem cells (iPSCs) hold enormous potential as a tool to generate cells for tissue engineering and regenerative medicine. Since the initial report of iPSCs in 2006, many different methods have been developed in order to enhance the safety and efficiency of this technology. Recent studies indicate that the extracellular signals can promote the production of iPSCs, and even replace the Yamanaka factors. Noticeably, abundant evidences suggest that the insoluble microenvironment, including the culture substrate and neighboring cells, directly regulates the expression of core pluripotency genes and the epigenetic modification of the chromatins, hence impact the reprogramming dynamics...
January 12, 2018: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/29327488/isolation-of-human-photoreceptor-precursors-via-a-cell-surface-marker-panel-from-stem-cell-derived-retinal-organoids-and-fetal-retinae
#12
Jörn Lakowski, Emily Welby, Dimitri Budinger, Fabiana Di Marco, Valentina Di Foggia, James W B Bainbridge, Kyle Wallace, David M Gamm, Robin R Ali, Jane C Sowden
Loss of photoreceptor cells due to retinal degeneration is one of the main causes of blindness in the developed world. Although there is currently no effective treatment, cell replacement therapy using stem-cell-derived photoreceptor cells may be a feasible future treatment option. In order to ensure safety and efficacy of this approach, robust cell isolation and purification protocols must be developed. To this end, we previously developed a biomarker panel for the isolation of mouse photoreceptor precursors from the developing mouse retina and mouse embryonic stem cell cultures...
January 12, 2018: Stem Cells
https://www.readbyqxmd.com/read/29327201/allele-specific-biased-expression-of-the-cntn6-gene-in-ips-cell-derived-neurons-from-a-patient-with-intellectual-disability-and-3p26-3-microduplication-involving-the-cntn6-gene
#13
Maria M Gridina, Natalia M Matveeva, Veniamin S Fishman, Aleksei G Menzorov, Helen A Kizilova, Nikolay A Beregovoy, Igor I Kovrigin, Inna E Pristyazhnyuk, Igor P Oscorbin, Maxim L Filipenko, Anna A Kashevarova, Nikolay A Skryabin, Tatyana V Nikitina, Elena A Sazhenova, Ludmila P Nazarenko, Igor N Lebedev, Oleg L Serov
Copy number variations (CNVs) of the human CNTN6 gene caused by megabase-scale microdeletions or microduplications in the 3p26.3 region are often the cause of neurodevelopmental disorders, including intellectual disability and developmental delay. Surprisingly, patients with different copy numbers of this gene display notable overlapping of neuropsychiatric symptoms. The complexity of the study of human neuropathologies is associated with the inaccessibility of brain material. This problem can be overcome through the use of reprogramming technologies that permit the generation of induced pluripotent stem (iPS) cells from fibroblasts and their subsequent in vitro differentiation into neurons...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29323137/issues-with-the-specificity-of-immunological-reagents-for-nlrp3-implications-for-age-related-macular-degeneration
#14
Cassandra Kosmidou, Nikolaos E Efstathiou, Mien V Hoang, Shoji Notomi, Eleni K Konstantinou, Masayuki Hirano, Kosuke Takahashi, Daniel E Maidana, Pavlina Tsoka, Lucy Young, Evangelos S Gragoudas, Timothy W Olsen, Yuki Morizane, Joan W Miller, Demetrios G Vavvas
Contradictory data have been presented regarding the implication of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome in age-related macular degeneration (AMD), the leading cause of vision loss in the Western world. Recognizing that antibody specificity may explain this discrepancy and in line with recent National Institutes of Health (NIH) guidelines requiring authentication of key biological resources, the specificity of anti-NLRP3 antibodies was assessed to elucidate whether non-immune RPE cells express NLRP3...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321513/tousled-like-kinase-1-is-a-negative-regulator-of-core-transcription-factors-in-murine-embryonic-stem-cells
#15
Jina Lee, Min Seong Kim, Su Hyung Park, Yeun Kyu Jang
Although the differentiation of pluripotent cells in embryonic stem cells (ESCs) is often associated with protein kinase-mediated signaling pathways and Tousled-like kinase 1 (Tlk1) is required for development in several species, the role of Tlk1 in ESC function remains unclear. Here, we used mouse ESCs to study the function of Tlk1 in pluripotent cells. The knockdown (KD)-based Tlk1-deficient cells showed that Tlk1 is not essential for ESC self-renewal in an undifferentiated state. However, Tlk1-KD cells formed irregularly shaped embryoid bodies and induced resistance to differentiation cues, indicating their failure to differentiate into an embryoid body...
January 10, 2018: Scientific Reports
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
#16
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/29321049/human-liver-organoids-generated-with-single-donor-derived-multiple-cells-rescue-mice-from-acute-liver-failure
#17
Yun-Zhong Nie, Yun-Wen Zheng, Miyuki Ogawa, Etsuko Miyagi, Hideki Taniguchi
BACKGROUND: Acute liver failure (ALF) is a life-threatening disease with a high mortality rate. However, there are limited treatments or devices available for ALF therapy. Here, we aimed to develop a new strategy for ALF treatment by transplanting functional liver organoids (LOs) generated from single donor-derived human induced pluripotent stem cell (hiPSC) endoderm, endothelial cells (ECs), and mesenchymal cells (MCs). METHODS: First, we isolated ECs and MCs from a single donor umbilical cord (UC) through enzyme digestion and characterized the UC-ECs and UC-MCs by flow cytometry...
January 10, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29320756/generation-of-an-induced-pluripotent-stem-cell-line-from-an-adult-male-with-45-x-46-xy-mosaicism
#18
Yumei Luo, Detu Zhu, Xiangye Xu, Lingxia Ge, Xiaofang Sun, Guokai Chen, Yaoyong Chen
Turner syndrome (TS) with 45,X/46,XY mosaic karyotype is a rare sex chromosome disorder with an occurrence of 0.15‰ at birth. We report the generation of an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a Chinese adult male with 45,X/46,XY mosaicism. The iPSC line retains the original 45,X/46,XY mosaic karyotype, expresses pluripotency markers and undergoes trilineage differentiation. Therefore, it offers an unprecedented cellular model to investigate the profound symptoms like infertility of TS in the male, and serve as a useful tool to develop therapies for the disease...
January 5, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29320747/identification-of-cardiomyocyte-fated-progenitors-from-human-induced-pluripotent-stem-cells-marked-with-cd82
#19
Masafumi Takeda, Yasuharu Kanki, Hidetoshi Masumoto, Shunsuke Funakoshi, Takeshi Hatani, Hiroyuki Fukushima, Akashi Izumi-Taguchi, Yusuke Matsui, Teppei Shimamura, Yoshinori Yoshida, Jun K Yamashita
Here, we find that human-induced pluripotent stem cell (hiPSC)-derived cardiomyocyte (CM)-fated progenitors (CFPs) that express a tetraspanin family glycoprotein, CD82, almost exclusively differentiate into CMs both in vitro and in vivo. CD82 is transiently expressed in late-stage mesoderm cells during hiPSC differentiation. Purified CD82+ cells gave rise to CMs under nonspecific in vitro culture conditions with serum, as well as in vivo after transplantation to the subrenal space or injured hearts in mice, indicating that CD82 successfully marks CFPs...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29318513/targeted-elimination-of-mutant-mitochondrial-dna-in-melas-ipscs-by-mitotalens
#20
Yi Yang, Han Wu, Xiangjin Kang, Yanhui Liang, Ting Lan, Tianjie Li, Tao Tan, Jiangyun Peng, Quanjun Zhang, Geng An, Yali Liu, Qian Yu, Zhenglai Ma, Ying Lian, Boon Seng Soh, Qingfeng Chen, Ping Liu, Yaoyong Chen, Xiaofang Sun, Rong Li, Xiumei Zhen, Ping Liu, Yang Yu, Xiaoping Li, Yong Fan
Mitochondrial diseases are maternally inherited heterogeneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruction of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells (MiPSCs) that harbored a high proportion of m...
January 9, 2018: Protein & Cell
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