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Stem Cell Research

Nada Sagga, Lucia Kuffová, Neil Vargesson, Lynda Erskine, J Martin Collinson
Limbal epithelial stem cells (LESCs) are believed to be responsible for corneal epithelial maintenance and repair after injury, but their activity has never been properly quantified in aging or wounded eyes. In this study, labelling with thymidine analogues, 5-iodo-2'-deoxyuridine (IdU), 5-chloro-2'-deoxyuridine (CldU) and 5-ethynyl-2'-deoxyuridine (EdU), was used to estimate cell-cycle time of the corneal and limbal epithelia in wild-type eyes, comparing aging (12 months) and young adult (8 week) mice...
November 5, 2018: Stem Cell Research
Sara Vallejo-Diez, Aarne Fleischer, José María Martín-Fernández, Almudena Sánchez-Gilabert, Daniel Bachiller
Mucopolysaccharydosis IIIB is the second most frequent form of Sanfilippo syndrome, a degenerative, pediatric lysosomal storage disease (LSD) characterized by severe neurological disorders and death. We have generated two iPSCs lines derived from dermal fibroblast from a MPSIIIB homozygous (P358L) donor. Cells were reprogrammed with OriP/EBNA1-based episomal plasmids containing: OCT3/4, SOX2, KLF4, L-MYC, LIN28, BCL-xL and shp53. Both cell lines are homozygous for the P358L mutation of the α-N-acetylglucosaminidase (NAGLU) gene, have normal karyotype, are free of plasmid integration, express high levels of pluripotency-associated markers and can differentiate into the three germ layers...
November 1, 2018: Stem Cell Research
Osele Ciampi, Elena Romano, Ariela Benigni, Susanna Tomasoni
Focal Segmental Glomerulosclerosis (FSGS) is the typical renal histologic lesion in familial steroid-resistant nephrotic syndrome, for which there is currently no treatment. Dysfunction of the glomerular podocyte, a specialized cell that forms the glomerular filtration barrier, is central in the pathogenesis of FSGS. Here, we reported the generation of two isogenic iPS cell lines from a patient affected by FSGS, carrying the c.565G > A mutation in the PAX2 gene. The iPS cell lines we generated expressed pluripotency markers at the mRNA and protein levels and differentiated into all three germ layers...
October 29, 2018: Stem Cell Research
Thomas Klein, Lisa Henkel, Katharina Klug, Chee Keong Kwok, Eva Klopocki, Nurcan Üçeyler
In this study, we report the human induced pluripotent stem cell line (iPSC) HSAN5-T203 M-iPSC, generated from human dermal fibroblasts (HDF) of a woman carrying a heterozygous c.608C > T mutation in the nerve growth factor gene potentially associated with hereditary sensory and autonomic neuropathy type 5 (HSAN5). HDF were reprogrammed using transient expression of key transcription factors for pluripotency and immune evasion via transfection of synthetic mRNA and miRNA. HSAN5-T203 M-iPSC retained the disease-associated genotype c...
October 12, 2018: Stem Cell Research
Candela Machuca, Angel Vilches, Eleonora Clemente, Samuel Ignacio Pascual-Pascual, Arantxa Bolinches-Amorós, Ana Artero Castro, Carmen Espinos, Marian Leon, Pavla Jendelova, Slaven Erceg
The human iPSC cell line, CARS-FiPS4F1 (ESi064-A), derived from dermal fibroblast from the apparently healthy carrier of the mutation of 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. This iPSC line can be used as control for Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) disease.
October 12, 2018: Stem Cell Research
Rashmi Tandon, Björn Brändl, Natalya Baryshnikova, Alexandro Landshammer, Laura Steenpaß, Oliver Keminer, Ole Pless, Franz-Josef Müller
Two isogenic hiPSC lines, ZIPi013-B and ZIPi013-E, were generated by reprogramming fetal dermal fibroblasts with episomal vectors. Previously, the same fetal fibroblasts were reprogrammed multiple times in a study comparing other reprogramming methods. As a consequence, the genomes have been sequenced multiple times. Both new cell lines offer the opportunity to study basic stem cell biology and model human disease. They can be applied as reference cell lines for creating isogenic clones bearing disease mutations on a well-characterized genomic background, as both cell lines have demonstrated excellent differentiation capacity in multiple labs...
October 12, 2018: Stem Cell Research
Javier Linares, Leyre López-Muneta, Estibaliz Arellano-Viera, Purificación Ripalda-Cemboráin, Elena Iglesias, Gloria Abizanda, Xabier L Aranguren, Felipe Prósper, Xonia Carvajal-Vergara
Islet-1 (Isl1) is a transcription factor essential for life expressed in specific cells with different developmental origins. We have generated iPSC lines from fibroblasts of the transgenic Ai6 x Isl1-Cre (Ai6IslCre) mouse. Here we describe the complete characterization of four iPSC lines: ATCi-Ai6IslCre10, ATCi-Ai6IslCre35, ATCi-Ai6IslCre74 and ATCi-Ai6IslCre80.
October 11, 2018: Stem Cell Research
Mohamed Jamal, Sara L Lewandowski, Matthew L Lawton, George T-J Huang, Laertis Ikonomou
The introduction and widespread adoption of induced pluripotent stem cell (iPSC) technology has opened new avenues for craniofacial regenerative medicine. Neural crest cells (NCCs) are the precursor population to many craniofacial structures, including dental and periodontal structures, and iPSC-derived NCCs may, in the near future, offer an unlimited supply of patient-specific cells for craniofacial repair interventions. Here, we used an established protocol involving simultaneous Wnt signaling activation and TGF-β signaling inhibition to differentiate three human iPSC lines to cranial NCCs...
October 10, 2018: Stem Cell Research
Daniele Pollini, Rosa Loffredo, Marina Cardano, Luciano Conti, Serena Lattante, Angelantonio Notarangelo, Mario Sabatelli, Alessandro Provenzani
Fibroblasts isolated from an Amyotrophic Lateral Sclerosis (ALS)-patient carrying a mutation in Matrin-3 (p.Q66K -MATR3) gene were reprogrammed to the pluripotency stage by using non-integrating episomal plasmids. We generated the Q66K#44DRM induced pluripotent stem cell (iPSC) line that showed regular karyotype, expressed pluripotency-associated markers and were able to properly differentiate into the three germ layers. The heterozygous missense mutation in the MATR3 gene (p.Q66K), which is associated to ALS disease, was present in the generated iPSC line...
October 6, 2018: Stem Cell Research
Friedrich Erdlenbruch, Jürgen Rohwedel, Philipp Ralfs, Antonia Thomitzek, Jan Kramer, Figen Cakiroglu
The human iPS cell line VUZUZLi001-A (hVH-1) was generated from human foreskin fibroblasts to be used as a control line. Reprogramming was performed by retroviral transduction of reprogramming factors OCT4, SOX2, KLF4 and c-MYC. Resource table.
October 6, 2018: Stem Cell Research
Elaine L Ferguson, Sameza Naseer, Lydia C Powell, Joseph Hardwicke, Fraser I Young, Bangfu Zhu, Qian Liu, Bing Song, David W Thomas
An essential aspect of stem cell in vitro culture and in vivo therapy is achieving sustained levels of growth factors to support stem cell survival and expansion, while maintaining their multipotency and differentiation potential. This study investigated the ability of dextrin (~74,000 g/mol; 27.8 mol% succinoylation) conjugated to epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF; or FGF-2) (3.9 and 6.7% w/w protein loading, respectively) to support the expansion and differentiation of stem cells in vitro via sustained, controllable growth factor release...
October 6, 2018: Stem Cell Research
Ying Wang, Qiang Fen, Hongxiang Yu, Haixia Qiu, Xiquan Ma, Ying Lei, Jian Zhao
A 32-year old Bipolar Disorder (BD) 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 BD...
October 6, 2018: Stem Cell Research
Mira Holliday, Samantha Barratt Ross, Seakcheng Lim, Christopher Semsarian
Hypertrophic cardiomyopathy is an inherited cardiomyopathy with a prevalence of up to 1 in 200, which can result in significant morbidity and mortality. An iPSC line was generated from peripheral blood mononuclear cells obtained from the whole blood of a 58-year-old male with hypertrophic cardiomyopathy who carries the heterozygous pathogenic myosin binding protein C mutation p.Arg502Trp. Induced pluripotent stem cells express pluripotency markers, demonstrate trilineage differentiation potential, and display a normal karyotype...
October 6, 2018: Stem Cell Research
Dunja Lukovic, Ana Artero Castro, Marian León, Verónica Del Buey Furió, Marta Cortón, Carmen Ayuso, Slaven Erceg
The human induced pluripotent stem cell (hiPSC) line, derived from dermal fibroblasts from Leber congenital amaurosis patient with homozygous mutation c.265 T > C, p.Cys89Arg in aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) was generated by Sendai virus reprogramming. The generated hiPSC line was free of Sendai virus genes, had stable karyotype, carried the homozygous mutation, was immunopositive to pluripotency markers and able to generate all three germ layers upon embryoid body formation...
October 5, 2018: Stem Cell Research
Nickesha C Anderson, Meghan A Van Zandt, Swechhya Shrestha, Daniel B Lawrence, Jyoti Gupta, Christopher Y Chen, Felicia A Harrsch, Trinithas Boyi, Carolyn E Dundes, Gloster Aaron, Janice R Naegele, Laura Grabel
GABAergic interneuron dysfunction has been implicated in temporal lobe epilepsy (TLE), autism, and schizophrenia. Inhibitory interneuron progenitors transplanted into the hippocampus of rodents with TLE provide varying degrees of seizure suppression. We investigated whether human embryonic stem cell (hESC)-derived interneuron progenitors (hESNPs) could differentiate, correct hippocampal-dependent spatial memory deficits, and suppress seizures in a pilocarpine-induced TLE mouse model. We found that transplanted ventralized hESNPs differentiated into mature GABAergic interneurons and became electrophysiologically active with mature firing patterns...
October 5, 2018: Stem Cell Research
Luca Braccioli, Stephin J Vervoort, Gianmarco Puma, Cora H Nijboer, Paul J Coffer
SOX4 has been shown to promote neuronal differentiation both in the adult and embryonic neural progenitors. Ectopic SOX4 expression has also been shown to inhibit oligodendrocyte differentiation in mice, however the underlying molecular mechanisms remain poorly understood. Here we demonstrate that SOX4 regulates transcriptional targets associated with neural development in neural stem cells (NSCs), reducing the expression of genes promoting oligodendrocyte differentiation. Interestingly, we observe that SOX4 levels decreased during oligodendrocyte differentiation in vitro...
October 4, 2018: Stem Cell Research
Ahmed E Hegab, Mari Ozaki, Fatma Y Meligy, Shizuko Kagawa, Makoto Ishii, Tomoko Betsuyaku
High fat diet (HFD) decreases the lifespan of mice, and is a risk factor for several human diseases. Here, we investigated the effects of a HFD on lung epithelial and stem cells and its interaction with aging. Young and old mice were fed with either a standard diet (SD) or a HFD then their trachea and lung were examined for histological changes, inflammation, and mitochondrial function. Their stem cell function was examined using the in vitro organoid/colony forming efficiency (CFE) assay. Aging reduced the number of tracheal basal and alveolar type-2 (AT2) cells...
October 4, 2018: Stem Cell Research
Ruthellen H Anderson, Jason G Kerkvliet, Jaelin J Otta, Alan D Ross, Patricia C Leiferman, Adam D Hoppe, Kevin R Francis
The most highly studied endocytic pathway, clathrin-dependent endocytosis, mediates a wide range of fundamental processes including nutrient internalization, receptor recycling, and signal transduction. In order to model tissue specific and developmental aspects of this process, CRISPR/Cas9 genomic editing was utilized to fluorescently label the C-terminus of clathrin light chain A (CLTA) within the phenotypically normal, parental CRMi001-A human induced pluripotent stem cell line. Successfully edited cells were isolated by fluorescently activated cell sorting, remained karyotypically normal, and maintained their differentiation potential...
October 3, 2018: Stem Cell Research
Yen-Hui Chan, Yen-Fu Cheng, You-Tzung Chen, Cheng-Yen Huang, Chin-Hsien Lin, Chin-Ju Hu, Ying-Chang Lu, Chen-Chi Wu, Chuan-Jen Hsu
Recessive mutations in the GJB2 gene are the most common genetic cause of hearing loss in humans. By using the Sendai-virus delivery system, we generated induced pluripotent stem cells (iPSCs) from the peripheral blood mononuclear cells of a female patient with the p.V37I (c.109G > A) mutation, a GJB2 mutation highly prevalent in the Asian population. The resulting iPSCs had a normal karyotype. The iPSCs also showed pluripotency, as confirmed by immunofluorescence staining, and differentiated into the three germ layers in vivo...
October 3, 2018: Stem Cell Research
Brittany E Jewell, Mo Liu, Linchao Lu, Ruoji Zhou, Jian Tu, Dandan Zhu, Zijun Huo, An Xu, Donghui Wang, Helen Mata, Weidong Jin, Weiya Xia, Pulivarthi H Rao, Ruiying Zhao, Mien-Chie Hung, Lisa L Wang, Dung-Fang Lee
The DNA helicase RECQL4 is known for its roles in DNA replication and repair. RECQL4 mutations cause several genetic disorders including Rothmund-Thomson syndrome (RTS), characterized by developmental defects and predisposition to osteosarcoma. Here we reprogrammed fibroblasts with a heterozygous RECQL4 mutation (c.1878 + 32_1878 + 55del24) to induced pluripotent stem cells (iPSCs). These iPSCs are pluripotent and are able to be differentiated into all three germ layers, providing a novel tool to further interrogate the role of RECQL4 DNA helicase in vitro...
October 2, 2018: Stem Cell Research
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