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Stem Cell Research

Benedetta Ermon, Claudia B Volpato, Giada Cattelan, Rosamaria Silipigni, Marina Di Segni, Chiara Cantaloni, Michela Casella, Peter P Pramstaller, Giulio Pompilio, Elena Sommariva, Viviana Meraviglia, Alessandra Rossini
Arrhythmogenic Cardiomyopathy (ACM) is an inherited cardiac disease characterized by arrhythmias and fibro-fatty replacement in the ventricular myocardium. Causative mutations are mainly reported in desmosomal genes, especially in plakophilin2 (PKP2). Here, using a virus-free reprogramming approach, we generated induced pluripotent stem cells (iPSCs) from skin fibroblasts of one ACM patient carrying the frameshift heterozygous PKP2 mutation c.2569_3018del50. The iPSC line (EURACi004-A) showed the typical morphology of pluripotent cells, possessed normal karyotype and exhibited pluripotency markers and trilineage differentiation potential, including cardiomyogenic capability...
September 6, 2018: Stem Cell Research
Elisa Maria Turco, Ersilia Vinci, Filomena Altieri, Daniela Ferrari, Barbara Torres, Marina Goldoni, Giuseppe Lamorte, Ada Maria Tata, Gianluigi Mazzoccoli, Diana Postorivo, Matteo Della Monica, Laura Bernardini, Angelo Luigi Vescovi, Jessica Rosati
CHRNA7, encoding the neuronal alpha7 nicotinic acetylcholine receptor (a7nAChR), is highly expressed in the brain, particularly in the hippocampus. It is situated in the 15q13.3 chromosome region, frequently associated with a Copy Number Variation (CNV), which causes its duplication or deletion. The clinical significance of CHRNA7 duplications is unknown so far, but there are several research data suggesting that they may be pathogenic, with reduced penetrance. We have produced an iPS cell line from a single healthy donor's fibroblasts carrying a 15q13...
September 6, 2018: Stem Cell Research
Ying Xie, Eun-Sil Park, Dongxi Xiang, Zhe Li
A recent paradigm shift in ovarian cancer research is the finding that many ovarian cancers may originate from fallopian tube epithelial (FTE) cells. As tissue stem and progenitor cells often serve as cells of origin of cancer, a better understanding of FTE stem/progenitor cells and how they become transformed is essential for early detection and prevention of ovarian cancer. To facilitate study of FTE stem/progenitor cells in model systems, we established an organoid culture system for mouse FTE cells. We find that EPCAM+ mouse FTE cells can be stably cultured long-term under a minimal condition of activated EGF signaling and suppressed TGFbeta signaling...
August 25, 2018: Stem Cell Research
Ying Wang, Chuanyuan Kang, Hongxiang Yu, Jing Fen, Xiquan Ma, Ying Lei, Jian Zhao
A 32-year old Obsessive-Compulsive Disorder (OCD) male patient donated his Peripheral blood mononuclear cells (PBMC). The non-integrating episomal vector system used to reprogram 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. Our model might offer a good platform to further study the pathological mechanisms, to identify early biomarkers, and also for drug testing studies in OCD...
August 24, 2018: Stem Cell Research
Benjamin Fischer, Anna Meier, Annika Dehne, Aseem Salhotra, Thao Anh Tran, Sascha Neumann, Katharina Schmidt, Ina Meiser, Julia C Neubauer, Heiko Zimmermann, Luca Gentile
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are an invaluable tool for both basic and translational cardiovascular research. The potential that these cells hold for therapy, disease modeling and drug discovery is hampered by several bottlenecks that currently limit both the yield and the efficiency of cardiac induction. Here, we present a complete workflow for the production of ready-to-use hiPSC-CMs in a dynamic suspension bioreactor. This includes the efficient and highly reproducible differentiation of hiPSCs into cardiospheres, which display enhanced physiological maturation compared to static 3D induction in hanging drops, and a novel papain-based dissociation method that offers higher yield and viability than the broadly used dissociation reagents TrypLE and Accutase...
August 24, 2018: Stem Cell Research
Akihide Kamiya, Hiromi Chikada, Kinuyo Ida, Emi Ando, Kota Tsuruya, Tatehiro Kagawa, Yutaka Inagaki
In the developing liver, bile duct structure is formed through differentiation of hepatic progenitor cells (HPC) into cholangiocytes. A subtype of polycystic liver diseases characterized by uncontrolled expansion of bile ductal cells is caused by genetic abnormalities such as in that of protein kinase C substrate 80 K-H (PRKCSH). In this study, we aimed to mimic the disease process in vitro by genome editing of the PRKCSH locus in human inducible pluripotent stem (iPS) cells. A proportion of cultured human iPS cell-derived CD13+ CD133+ HPC differentiated into CD13- cells...
August 24, 2018: Stem Cell Research
Yutong Liu, Yiqun Wang, Xifan He, Sheng Zhang, Kai Wang, Hanjiang Wu, Lin Chen
The adipogenic differentiation of adipose tissue-derived mesenchymal stem cells (ADSCs) is a critical issue in many obesity-related disorders and it can be regulated by a crucial transcription factor, CCAAT enhancer binding protein α (C/EBP-α). Apart from, the involvement of non-coding RNAs in adipogenic differentiation has also been reported. As we know, Terminal differentiation-induced ncRNA (TINCR) is required in somatic tissue differentiation. Recently, we found that TINCR could modulate adipogenic differentiation in hADSCs...
August 23, 2018: Stem Cell Research
Aishwarya G Nadadhur, Prisca S Leferink, Dwayne Holmes, Lisa Hinz, Paulien Cornelissen-Steijger, Lisa Gasparotto, Vivi M Heine
The neural tube consists of neural progenitors (NPs) that acquire different characteristics during gestation due to patterning factors. However, the influence of such patterning factors on human pluripotent stem cells (hPSCs) during in vitro neural differentiation is often unclear. This study compared neural induction protocols involving in vitro patterning with single SMAD inhibition (SSI), retinoic acid (RA) administration and dual SMAD inhibition (DSI). While the derived NP cells expressed known NP markers, they differed in their NP expression profile and differentiation potential...
August 23, 2018: Stem Cell Research
Yanlin Wang, Zhilei Wang, Huifang Sun, Changhe Shi, Jing Yang, Yutao Liu, Han Liu, Shoutao Zhang, Li Zhang, Yuming Xu, Jin Zhang
Myotonic dystrophy type 1 (DM1) is a dominantly inherited neurodegenerative disease caused by a CTG repeat expansion close to the DMPK gene. The fibroblasts from a patient with DM1 were successfully converted to induced pluripotent stem cells (iPSCs), designated ZZUi006-A, by employing episomal plasmids expressing OCT3/4, SOX2, KLF4, LIN28, L-MYC. The ZZUi006-A cell line may provide a robust platform for further study of DM1 pathogenesis as well as drug testing and gene therapy research.
August 22, 2018: Stem Cell Research
Erika Gaspari, Annika Franke, Diana Robles-Diaz, Robert Zweigerdt, Ingo Roeder, Thomas Zerjatke, Henning Kempf
With their capability to self-renew and differentiate into derivatives of all three germ layers, human pluripotent stem cells (hPSCs) offer a unique model to study aspects of human development in vitro. Directed differentiation towards mesendodermal lineages is a complex process, involving transition through a primitive streak (PS)-like stage. We have recently shown PS-like patterning from hPSCs into definitive endoderm, cardiac as well as presomitic mesoderm by only modulating the bulk cell density and the concentration of the GSK3 inhibitor CHIR99021, a potent activator of the WNT pathway...
August 18, 2018: Stem Cell Research
Ponthip Potirat, Methichit Wattanapanitch, Pakpoom Kheolamai, Surapol Issaragrisil
Human induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMNCs) isolated from a 26-year-old healthy subject to use as a control group for the iPSC line carrying compound heterozygote for mutation in KLF1 gene. The cells were reprogrammed using integration-free method, Sendai viral (SeV) vectors containing KOS, hc-MYC and hKLF4. The established iPSC line (MUSIi007-A) exhibited a normal karyotype, expressed pluripotent markers and displayed in vitro and in vivo differentiation potential into cells of three embryonic germ layers...
August 17, 2018: Stem Cell Research
Jürgen Stumm, Pedro Vallecillo-García, Sophie Vom Hofe-Schneider, David Ollitrault, Heinrich Schrewe, Aris N Economides, Giovanna Marazzi, David A Sassoon, Sigmar Stricker
Fibro-adipogenic progenitors (FAPs) are resident mesenchymal progenitors in adult skeletal muscle that support muscle repair, but also give rise to fibrous and adipose infiltration in response to disease and chronic injury. FAPs are identified using cell surface markers that do not distinguish between quiescent FAPs and FAPs actively engaged in the regenerative process. We have shown previously that FAPs are derived from cells that express the transcription factor Osr1 during development. Here we show that adult FAPs express Osr1 at low levels and frequency, however upon acute injury FAPs reactivate Osr1 expression in the injured tissue...
August 10, 2018: Stem Cell Research
Xiaofan Zhu, Aojie Cai, Jingjing Meng, Lina Liu, Siying Cui, Suzhen Qu, Junhong Zhao, Ning Liu, Xiangdong Kong
Duchenne muscular dystrophy (DMD) is a common X-linked recessive disorder for which there is no present cure. In this paper, we reported the generation of ZZUi008-A, an induced pluripotent stem cell(iPSC) line derived from chorionic villus(CV) cells of a fetus with a deletion mutation in exon 33 of the dystrophin gene (DMD). The cell line was generated using feeder-free and virus-free conditions, and the established cell line retains the original DMD mutation, a normal karyotype, expresses pluripotency markers, able to differentiate into three lineages...
July 17, 2018: Stem Cell Research
Candela Machuca Arellano, Angel Vilches, Eleonora Clemente, Samuel Ignacio Pascual-Pascual, Arantxa Bolinches-Amorós, Ana Artero Castro, Carmen Espinos, Marian Leon Rodriguez, Pavla Jendelova, Slaven Erceg
The human iPSC cell line, ARS-FiPS4F1 (ESi063-A), derived from dermal fibroblast from the patient autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) caused by mutations on the gene SACSIN, was generated by non-integrative reprogramming technology using OCT3/4, SOX2, CMYC and KLF4 reprogramming factors. The pluripotency was assessed by immunocytochemistry and RT-PCR. Differentiation capacity was verified in vitro. This iPSC line can be further differentiated toward affected cells to better understand molecular mechanisms of disease and pathophysiology...
August 2018: Stem Cell Research
T V Nikitina, A G Menzorov, A A Kashevarova, M M Gridina, A A Khabarova, Yu S Yakovleva, M E Lopatkina, E A Kizilova, S A Vasilyev, O L Serov, I N Lebedev
Skin fibroblasts from a patient with intellectual disability and ring chromosome 22 were reprogrammed into induced pluripotent stem cells (iPSCs) to establish a clonal stem cell lines, IMGTi001-A (iTAF5-29) and IMGTi001-B (iTAF5-32). Because of ring chromosome mitotic instability these cell lines show mosaic karyotypes with 46,XX,r(22) in >83% cells, 45,XX,-22 as minor class and sporadically cells with other karyotypes. Differentiation in derivatives of all three germ layers was shown in teratoma assay for IMGTi001-A, and in embryoid bodies for both cell lines...
August 2018: Stem Cell Research
Yuko Arioka, Itaru Kushima, Daisuke Mori, Norio Ozaki
Duplications at the 15q11.2-q13.1 region are associated with psychiatric disorders such as developmental delay and autism spectrum disorder. However, the specific influence of these duplications on human neuronal cells remains unclear. Here we generated induced pluripotent stem cells (iPSCs) derived from a patient with 15q11.2-q13.1 duplication syndrome. The generated iPSCs carried 15q11.2-q13.1 duplication and showed typical iPSC morphology and pluripotency marker expression, and the capacity to differentiate into three germ layers...
August 2018: Stem Cell Research
Caroline Amalie Brunbjerg Hey, Katarina Beata Saltõkowa, Lasse Jonsgaard Larsen, Zeynep Tümer, Karen Brøndum-Nielsen, Karen Grønskov, Tina Duelund Hjortshøj, Lisbeth Birk Møller
Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy with a wide range of symptoms including obesity, retinal dystrophy, polycystic kidney disease, polydactyly, hypogonadism and learning difficulties. Here we describe the successful generation of an induced pluripotent stem cell (iPSC) KCi001-A from a BBS patient compound heterozygous for two disease causing BBS1 variants c.1169T>G, p. (Met390Arg)/c.1135G>C, p.(Gly370Arg). Resource table.
August 2018: Stem Cell Research
Huilin Li, Haiyun Pei, Jiqin Nie, Mingyi Qu, Zeng Fan, Yali Jia, Lijuan He, Xue Nan, Wen Yue, Xuetao Pei
Primary arterial endothelial cell (AEC) is an attractive source of tissue-engineered blood vessels for therapeutic transplantation in vascular disease. However, scarcity of donor tissue, inability of proliferation and undergo de-differentiation in culture remain major obstacles. We derived a stable induced pluripotent stem cell (iPSC) line possessed all the characteristics of pluripotent state from human umbilical arterial endothelial cells by transduction of four human transcription factors (Oct4, Sox2, Klf4, and c-Myc) using sendai virus vectors...
August 2018: Stem Cell Research
Sonia Sanz Muñoz, Rachelle Balez, Mauricio E Castro Cabral-da-Silva, Tracey Berg, Martin Engel, Monique Bax, Dzung Do-Ha, Claire H Stevens, Mark Greenough, Ashley Bush, Lezanne Ooi
The induced pluripotent stem cell (iPSC) lines UOWi002-A and UOWi003-A were reprogrammed from dermal fibroblasts via mRNA transfection. Dermal fibroblasts from a 56 year old female caucasian familial Alzheimer's disease patient carrying A246E mutation in the PSEN1 gene (familial AD3, autopsy confirmed Alzheimer's disease) and a 75 year old female non-demented control from the same family bearing the wild-type PSEN1 A246 genotype were obtained from the Coriell Institute (AG06848 and AG06846, respectively)...
August 2018: Stem Cell Research
Thomas Klein, Katharina Günther, Chee Keong Kwok, Frank Edenhofer, Nurcan Üçeyler
Human dermal fibroblasts (HDF) were isolated from the skin punch biopsy of a 25-year-old woman with Fabry disease (FD), carrying a heterozygous c.708 G > C missense mutation in the alpha-galactosidase A gene. HDF were reprogrammed to induced pluripotent stem cells (iPSC) using synthetic mRNA, preventing the alteration of the genome and retaining the original genotype. FD-W236C-iPSC (UKWNLi001-A) showed typical human embryonic stem cell (hESC)-like morphology, expressed all analyzed pluripotency-associated markers, could be differentiated into cells from all three germ layers, and demonstrated a normal female karyotype...
August 2018: Stem Cell Research
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