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Induced pluripotent stem

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https://www.readbyqxmd.com/read/27932790/motor-neurons-derived-from-als-related-mouse-ips-cells-recapitulate-pathological-features-of-als
#1
Ju-Hwang Park, Hang-Soo Park, Sunghoi Hong, Seongman Kang
Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disease characterized by the loss of motor neurons in the spinal cord and brain. Mutations in Cu/Zn superoxide dismutase 1 (SOD1) are known to induce ALS. Although many research models have been developed, the exact pathological mechanism of ALS remains unknown. The recently developed induced pluripotent stem (iPS) cell technology is expected to illuminate the pathological mechanisms and new means of treatment for neurodegenerative diseases...
December 9, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27932383/comparison-of-the-glycosphingolipids-of-human-induced-pluripotent-stem-cells-and-human-embryonic-stem-cells
#2
Karin Säljö, Angela Barone, Dzeneta Vizlin-Hodzic, Bengt R Johansson, Michael E Breimer, Keiko Funa, Susann Teneberg
High expectations are held for human-induced pluripotent stem cells (hiPSC) since they are established from autologous tissues thus overcoming the risk of allogeneic immune rejection when used in regenerative medicine. However, little is known regarding the cell-surface carbohydrate antigen profile of hiPSC compared with human embryonic stem cells (hESC). Here, glycosphingolipids were isolated from an adipocyte-derived hiPSC line, and hiPSC and hESC glycosphingolipids were compared by concurrent characterization by binding assays with carbohydrate-recognizing ligands and mass spectrometry...
December 8, 2016: Glycobiology
https://www.readbyqxmd.com/read/27931510/generation-of-equine-induced-pluripotent-stem-cells-and-analysis-of-their-therapeutic-potential-for-muscle-injuries
#3
Eun-Mi Lee, Ah-Young Kim, Eun-Joo Lee, Jin-Kyu Park, Se-Il Park, Ssang-Goo Cho, Hong Kyun Kim, Shin-Yoon Kim, Kyu-Shik Jeong
Horse health has become a major concern with the expansion of horse-related industries and sports; the importance of healthy muscles for horse performance and daily activities is undisputed. Here we generated equine-induced pluripotent stem cells (E-iPSCs) by reprogramming equine adipose-derived stem cells (E-ADSCs) into iPSCs using a polycistronic lentiviral vector encoding four transcription factors (i.e., Oct4, Sox2, Klf4, and c-Myc) and then examined their pluripotent characteristics. Subsequently, established E-iPSCs were transplanted into muscle-injured Rag/mdx mice...
November 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27931506/neural-stem-cells-derived-from-human-parthenogenetic-stem-cells-engraft-and-promote-recovery-in-a-nonhuman-primate-model-of-parkinsons-disease
#4
Rodolfo Gonzalez, Ibon Garitaonandia, Maxim Poustovoitov, Tatiana Abramihina, Caleb McEntire, Ben Culp, Jordan Attwood, Alexander Noskov, Trudy Christiansen-Weber, Marwa Khater, Sergio Mora-Castilla, Cuong To, Andrew Crain, Glenn Sherman, Andrey Semechkin, Louise C Laurent, John D Elsworth, John Sladek, Evan Y Snyder, D Eugene Redmond, Russell A Kern
Cell therapy has attracted considerable interest as a promising therapeutic alternative for patients with Parkinsons disease (PD). Clinical studies have shown that grafted fetal neural tissue can achieve considerable biochemical and clinical improvements in PD. However, the source of fetal tissue grafts is limited and ethically controversial. Human parthenogenetic stem cells offer a good alternative because they are derived from unfertilized oocytes without destroying potentially viable human embryos and can be used to generate an unlimited supply of neural cells for transplantation...
November 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27930666/development-of-pet-imaging-to-visualize-activated-macrophages-accumulated-in-the-transplanted-ipsc-derived-cardiac-myocytes-of-allogeneic-origin-for-detecting-the-immune-rejection-of-allogeneic-cell-transplants-in-mice
#5
Noriyuki Kashiyama, Shigeru Miyagawa, Satsuki Fukushima, Takuji Kawamura, Ai Kawamura, Shohei Yoshida, Akima Harada, Tadashi Watabe, Yasukazu Kanai, Koichi Toda, Jun Hatazawa, Yoshiki Sawa
Allogeneic transplantation (Tx) of induced pluripotent stem cells (iPSCs) is a promising tissue regeneration therapy. However, this inevitably induces macrophage-mediated immune response against the graft, limiting its therapeutic efficacy. Monitoring the magnitude of the immune response using imaging tools would be useful for prolonging graft survival and increasing the therapy longevity. Minimally invasive quantitative detection of activated macrophages by medical imaging technologies such as positron emission tomography (PET) imaging targets translocator protein (TSPO), which is highly expressed on mitochondrial membrane, especially in activated macrophage...
2016: PloS One
https://www.readbyqxmd.com/read/27929521/efficient-footprint-free-human-ipsc-genome-editing-by-consolidation-of-cas9-crispr-and-piggybac-technologies
#6
Gang Wang, Luhan Yang, Dennis Grishin, Xavier Rios, Lillian Y Ye, Yong Hu, Kai Li, Donghui Zhang, George M Church, William T Pu
Genome editing of human induced pluripotent stem cells (hiPSCs) offers unprecedented opportunities for in vitro disease modeling and personalized cell replacement therapy. The introduction of Cas9-directed genome editing has expanded adoption of this approach. However, marker-free genome editing using standard protocols remains inefficient, yielding desired targeted alleles at a rate of ∼1-5%. We developed a protocol based on a doxycycline-inducible Cas9 transgene carried on a piggyBac transposon to enable robust and highly efficient Cas9-directed genome editing, so that a parental line can be expeditiously engineered to harbor many separate mutations...
January 2017: Nature Protocols
https://www.readbyqxmd.com/read/27927750/mdm2-as-a-chromatin-modifier
#7
REVIEW
Magdalena Wienken, Ute M Moll, Matthias Dobbelstein
Mdm2 is the key negative regulator of the tumour suppressor p53, making it an attractive target for anti-cancer drug design. We recently identified a new role of Mdm2 in gene repression through its direct interaction with several proteins of the polycomb group (PcG) family. PcG proteins form polycomb repressive complexes PRC1 and PRC2. PRC2 (via EZH2) mediates histone 3 lysine 27 (H3K27) trimethylation, and PRC1 (via RING1B) mediates histone 2A lysine 119 (H2AK119) monoubiquitination. Both PRCs mostly support a compact and transcriptionally silent chromatin structure...
November 9, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27926879/in%C3%A2-vitro-derivation-and-propagation-of-spermatogonial-stem-cell-activity-from-mouse-pluripotent-stem-cells
#8
Yukiko Ishikura, Yukihiro Yabuta, Hiroshi Ohta, Katsuhiko Hayashi, Tomonori Nakamura, Ikuhiro Okamoto, Takuya Yamamoto, Kazuki Kurimoto, Kenjiro Shirane, Hiroyuki Sasaki, Mitinori Saitou
The in vitro derivation and propagation of spermatogonial stem cells (SSCs) from pluripotent stem cells (PSCs) is a key goal in reproductive science. We show here that when aggregated with embryonic testicular somatic cells (reconstituted testes), primordial germ cell-like cells (PGCLCs) induced from mouse embryonic stem cells differentiate into spermatogonia-like cells in vitro and are expandable as cells that resemble germline stem cells (GSCs), a primary cell line with SSC activity. Remarkably, GSC-like cells (GSCLCs), but not PGCLCs, colonize adult testes and, albeit less effectively than GSCs, contribute to spermatogenesis and fertile offspring...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926491/early-pathogenic-event-of-alzheimer-s-disease-documented-in-ipscs-from-patients-with-psen1-mutations
#9
Juan Yang, Hanzhi Zhao, Yu Ma, Guilai Shi, Jian Song, Yu Tang, Song Li, Ting Li, Nan Liu, Fan Tang, Junjie Gu, Lingling Zhang, Zhuohua Zhang, Xiaohui Zhang, Ying Jin, Weidong Le
Alzheimer's disease (AD) is the most common age-related dementia characterized by progressive neuronal loss. However, the molecular mechanisms for the neuronal loss is still debated. Here, we used induced pluripotent stem cells (iPSCs) derived from somatic cells of familial AD patients carrying PSEN1 mutations to study the early pathogenic event of AD. We found that premature neuronal differentiation with decreased proliferation and increased apoptosis occured in AD-iPSC-derived neural progenitor cells (AD-NPCs) once neuronal differentiation was initiated, together with higher levels of Aβ42 and phosphorylated tau...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925238/danshen-enhanced-cardioprotective-effect-of-cardioplegia-on-ischemia-reperfusion-injury-in-a-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-model
#10
Wei Wei, Yiwei Liu, Qiang Zhang, Yangming Wang, Xiaoling Zhang, Hao Zhang
Myocardial ischemia-reperfusion (I/R) injury is unavoidable during cardioplegic arrest and open-heart surgery. Danshen is one of the most popular traditional herbal medicines in China, which has entered the Food and Drug Administration-approved phase III clinical trial. This study was aimed to develop a human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) model to mimic I/R injury and evaluate the cardioprotective effect of regular cardioplegic solution with Danshen. hiPSC-CMs were cultured with the crystalloid cardioplegic solution (Thomas group) and Thomas solution with 2 or 10 µg/mL Danshen (Thomas plus Danshen groups)...
December 7, 2016: Artificial Organs
https://www.readbyqxmd.com/read/27925205/generation-of-insulin-producing-cells-from-human-induced-pluripotent-stem-cells-using-a-stepwise-differentiation-protocol-optimized-with-platelet-rich-plasma
#11
Seyed Ehsan Enderami, Yousef Mortazavi, Masoud Soleimani, Samad Nadri, Alireza Biglari, Reyhaneh Nassiri Mansour
Studies on patient-specific human-induced pluripotent stem cells (hiPSCs) as well as a series of autologous growth factors presumably will reveal their many benefits for cell base replacement therapy in type 1 diabetes mellitus (TIDM) patients in the future. For this purpose, we established a multistep protocol by adding platelet-rich plasma (PRP) that induce the hiPSCs into insulin-producing cells (IPCs). We present here a differentiation protocol consisting of five stages in two groups including protocol with PRP and without PRP...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27924227/otx2-impedes-self-renewal-of-porcine-ips-cells-through-downregulation-of-nanog-expression
#12
Ning Wang, Yaxian Wang, Youlong Xie, Huayan Wang
The transcription factor Otx2 acts as a negative switch in the regulation of transition from naive to primed pluripotency in mouse pluripotent stem cells. However, the molecular features and function of porcine OTX2 have not been well elucidated in porcine-induced pluripotent stem cells (piPSCs). By studying high-throughput transcriptome sequencing and interfering endogenous OTX2 expression, we demonstrate that OTX2 is able to downgrade the self-renewal of piPSCs. OTX2 is highly expressed in porcine brain, reproductive tissues, and preimplantation embryos, but is undetectable in fibroblasts and most somatic tissues...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27923595/vitamin-d-compounds-inhibit-cancer-stem-like-cells-and-induce-differentiation-in-triple-negative-breast-cancer
#13
REVIEW
Naing Lin Shan, Joseph Wahler, Hong Jin Lee, Min Ji Bak, Soumyasri Das Gupta, Hubert Maehr, Nanjoo Suh
Triple-negative breast cancer is one of the least responsive breast cancer subtypes to available targeted therapies due to the absence of hormonal receptors, aggressive phenotypes, and the high rate of relapse. Early breast cancer prevention may therefore play an important role in delaying the progression of triple-negative breast cancer. Cancer stem cells are a subset of cancer cells that are thought to be responsible for tumor progression, treatment resistance, and metastasis. We have previously shown that vitamin D compounds, including a Gemini vitamin D analog BXL0124, suppress progression of ductal carcinoma in situ in vivo and inhibit cancer stem-like cells in MCF10DCIS mammosphere cultures...
December 3, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27923539/the-roles-of-the-co-culture-of-mescs-with-pancreatic-islets-and-liver-stromal-cells-in-the-differentiation-of-definitive-endoderm-cells
#14
Hoveizi Elham, Fathi Fardin, Hashemitabar Mahmod
Embryonic stem (ES) cells have a pluripotent ability to differentiate into a variety of cell lineages in vitro. Investigating the roles of the co-culture of mouse embryonic stem cells (mESCs) with pancreatic islets (PL) and liver stromal cells (LSCs) in the differentiation of definitive endoderm (DE) cells was the purpose of this study. Here by using PL derived from adult mouse and LSCs derived from mouse fetal liver, we are trying to introduce a new protocol which is devoid of growth factors. We calculated mESCs indirectly for 7 days and then we analyzed the resulting cells regarding DE genes and protein expression using qRT-PCR and immunocytochemistry...
December 3, 2016: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/27923051/electrophysiological-characteristics-of-human-ipsc-derived-cardiomyocytes-for-the-assessment-of-drug-induced-proarrhythmic-potential
#15
Wataru Yamamoto, Keiichi Asakura, Hiroyuki Ando, Tomohiko Taniguchi, Atsuko Ojima, Takaaki Uda, Tomoharu Osada, Seiji Hayashi, Chieko Kasai, Norimasa Miyamoto, Hiroyuki Tashibu, Takashi Yoshinaga, Daiju Yamazaki, Atsushi Sugiyama, Yasunari Kanda, Kohei Sawada, Yuko Sekino
The aims of this study were to (1) characterize basic electrophysiological elements of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that correspond to clinical properties such as QT-RR relationship, (2) determine the applicability of QT correction and analysis methods, and (3) determine if and how these in-vitro parameters could be used in risk assessment for adverse drug-induced effects such as Torsades de pointes (TdP). Field potential recordings were obtained from commercially available hiPSC-CMs using multi-electrode array (MEA) platform with and without ion channel antagonists in the recording solution...
2016: PloS One
https://www.readbyqxmd.com/read/27923030/patient-derived-induced-pluripotent-stem-cells-in-cancer-research-and-precision-oncology
#16
Eirini P Papapetrou
Together with recent advances in the processing and culture of human tissue, bioengineering, xenotransplantation and genome editing, Induced pluripotent stem cells (iPSCs) present a range of new opportunities for the study of human cancer. Here we discuss the main advantages and limitations of iPSC modeling, and how the method intersects with other patient-derived models of cancer, such as organoids, organs-on-chips and patient-derived xenografts (PDXs). We highlight the opportunities that iPSC models can provide beyond those offered by existing systems and animal models and present current challenges and crucial areas for future improvements toward wider adoption of this technology...
December 6, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27922848/lung-regeneration-steps-toward-clinical-implementation-and-use
#17
Elizabeth A Calle, Katherine L Leiby, MichaSam B Raredon, Laura E Niklason
PURPOSE OF REVIEW: Whole lung tissue engineering is a relatively new area of investigation. In a short time, however, the field has advanced quickly beyond proof of concept studies in rodents and now stands on the cusp of wide-spread scale up to large animal studies. Therefore, this technology is ever closer to being directly clinically relevant. RECENT FINDINGS: The main themes in the literature include refinement of the fundamental components of whole lung engineering and increasing effort to direct induced pluripotent stem cells and lung progenitor cells toward use in lung regeneration...
December 5, 2016: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/27922138/mitomycin-c-treated-human-induced-pluripotent-stem-cells-as-a-safe-delivery-system-of-gold-nanorods-for-targeted-photothermal-therapy-of-gastric-cancer
#18
Meng Yang, Yanlei Liu, Wenxiu Hou, Xiao Zhi, Chunlei Zhang, Xinquan Jiang, Fei Pan, Yuming Yang, Jian Ni, Daxiang Cui
Human-induced pluripotent stem cells (iPS) possess an intrinsic tumor tropism ability. However, iPS cells are impeded in clinical applications of tumor therapy due to the formation of teratomas and their survival in normal organs such as the liver, lungs, spleen and kidneys. Mitomycin C (MMC) can overcome this limitation by suppressing iPS proliferation. Herein, we fabricated a safe delivery system of iPS cells treated with MMC loading with gold nanorods (AuNRs) for the targeted photothermal treatment of gastric cancer...
December 6, 2016: Nanoscale
https://www.readbyqxmd.com/read/27921262/a-new-era-of-disease-modeling-and-drug-discovery-using-induced-pluripotent-stem-cells
#19
REVIEW
Wonhee Suh
In 2006, Shinya Yamanaka first reported that in vitro reprogramming of somatic cells toward pluripotency was achieved by simple induction of specific transcription factors. Induced pluripotent stem cell (iPSC) technology has since revolutionized the ways in which we explore the mechanisms of human diseases and develop therapeutics. Here, I describe the recent advances in human iPSC-based disease modeling and drug discovery and discuss the current challenges. Additionally, I outline potential future applications of human iPSCs in classifying patients based on their response to drugs in clinical trials and elucidating optimal patient-specific therapeutic strategies, which will contribute to reduced attrition rates and the development of precision medicine...
December 5, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27920633/lesch-nyhan-syndrome-models-theories-and-therapies
#20
REVIEW
Scott Bell, Ilaria Kolobova, Liam Crapper, Carl Ernst
Lesch-Nyhan syndrome (LNS) is a rare X-linked disorder caused by mutations in HPRT1, an important enzyme in the purine salvage pathway. Symptoms of LNS include dystonia, gout, intellectual disability, and self-mutilation. Despite having been characterized over 50 years ago, it remains unclear precisely how deficits in hypoxanthine and guanine recycling can lead to such a profound neurological phenotype. Several studies have proposed different hypotheses regarding the etiology of this disease, and several treatments have been tried in patients, though none have led to a satisfactory explanation of the disease...
November 2016: Molecular Syndromology
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