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https://www.readbyqxmd.com/read/28741855/in-vivo-rescue-of-the-hematopoietic-niche-by-pluripotent-stem-cell-complementation-of-defective-osteoblast-compartments
#1
Rhiannon Chubb, James Oh, Alyssa K Riley, Takaharu Kimura, Sean M Wu, Joy Y Wu
Bone-forming osteoblasts play critical roles in supporting bone marrow hematopoiesis. Pluripotent stem cells (PSCs), including embryonic stem (ES) cells and induced pluripotent stem (iPS) cells, are capable of differentiating into osteoblasts. To determine the capacity of stem cells needed to rescue aberrant skeletal development and bone marrow hematopoiesis in vivo, we employed a skeletal complementation model. Mice deficient in Runx2, a master transcription factor for osteoblastogenesis, fail to form a mineralized skeleton and bone marrow...
July 25, 2017: Stem Cells
https://www.readbyqxmd.com/read/28724793/a-bag3-chaperone-complex-maintains-cardiomyocyte-function-during-proteotoxic-stress
#2
Luke M Judge, Juan A Perez-Bermejo, Annie Truong, Alexandre Js Ribeiro, Jennie C Yoo, Christina L Jensen, Mohammad A Mandegar, Nathaniel Huebsch, Robyn M Kaake, Po-Lin So, Deepak Srivastava, Beth L Pruitt, Nevan J Krogan, Bruce R Conklin
Molecular chaperones regulate quality control in the human proteome, pathways that have been implicated in many diseases, including heart failure. Mutations in the BAG3 gene, which encodes a co-chaperone protein, have been associated with heart failure due to both inherited and sporadic dilated cardiomyopathy. Familial BAG3 mutations are autosomal dominant and frequently cause truncation of the coding sequence, suggesting a heterozygous loss-of-function mechanism. However, heterozygous knockout of the murine BAG3 gene did not cause a detectable phenotype...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28699384/preclinical-safety-evaluation-of-allogeneic-ips-cell-based-therapy-in-a-swine-model-of-myocardial-infarction
#3
Carolina Gálvez-Montón, Carolina Soler-Botija, Oriol Iborra-Egea, Idoia Diaz-Guemes, Mercè Martí, Olalla Iglesias-Garcia, Cristina Prat-Vidal, Verónica Crisóstomo, Aida Llucià-Valldeperas, Isaac Perea-Gil, Santiago Roura, Francisco Miguel Sanchez Margallo, Ángel Raya, Antoni Bayés-Genís
The combination of biomatrices and induced pluripotent stem cell (iPSC) derivatives to aid repair and myocardial scar formation may soon become a reality for cardiac regenerative medicine. However, the tumor risk associated to residual undifferentiated cells remains an important safety concern of iPSC-based therapies. This concern is not satisfactorily addressed in xenotransplantation, which require immune suppression of the transplanted animal. Here, we assessed the safety of transplanting undifferentiated iPSC in an allogeneic setting...
July 12, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28695746/improvement-of-hepatogenic-differentiation-of-ips-cells-on-an-aligned-polyethersulfone-compared-to-random-nanofibers
#4
Maryam Mahmoodinia Maymand, Hamid Reza Soleimanpour-Lichaei, Abdolreza Ardeshirylajimi, Masoud Soleimani, Seyed Ehsan Enderami, Shahrzad Nojehdehi, Farkhondeh Behjati, Maryam Kabir Salmani
The application of stem cells holds great promises in cell and tissue transplants. This study was designed to compare the hepatogenic differentiation of iPSCs on aligned PES/COL versus random. Aligned and random PES/COL nanofibrus scaffolds were fabricated by electrospining and their surface modified through plasma treatment and collagen coating. The scaffolds were characterized using scanning electron microscopy (SEM) and ATR-FTIR. Morphology and biochemical activities of the differentiated hepatocyte-like cells (HLCs) were examined after 5 and 20 days of differentiation...
July 11, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28693263/role-of-microrna-296-3p-in-the-malignant-transformation-of-sinonasal-inverted-papilloma
#5
Tomohiko Kakizaki, Hiromitsu Hatakeyama, Yuji Nakamaru, Dai Takagi, Takatsugu Mizumachi, Tomohiro Sakashita, Satoshi Kano, Akihiro Homma, Satoshi Fukuda
Inverted papilloma (IP) is a benign tumor occurring in the nasal cavity and paranasal sinuses. It is reported that 5-15% of IPs undergo malignant transformation into squamous cell carcinoma (SCC), and the role of microRNAs (miRNA/miR) in this process remains to be elucidated. In the present study, whole miRNA profiles using samples of IP and SCC were investigated, in order to detect the function of miRNA in the carcinogenesis of IP. Samples from IPs (n=5) and SCC lesions (n=5), which arose from IPs, were used for miRNA analysis...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28679969/incidence-of-spontaneous-lymphomas-in-non-experimental-nod-shi-scid-il-2r%C3%AE-null-nog-mice
#6
Masahiko Yasuda, Tomoyuki Ogura, Takayuki Goto, Mika Yagoto, Yoko Kamai, Chie Shimomura, Nobuhito Hayashimoto, Yukito Kiyokawa, Hideki Shinohara, Riichi Takahashi, Kenji Kawai
Severely immunodeficient NOD/Shi-scid, IL-2Rγ(null) (NOG) mice provide an in vivo model for human cell/tissue transplantation studies. NOG mice were established by combining interleukin-2 receptor-γ chain knockout mice and NOD/Shi-scid mice. They exhibit a high incidence of thymic lymphomas and immunoglobulin (Ig) leakiness. In this study, we assessed the incidence of malignant lymphomas and the occurrence of leakiness in 2,184 non-experimental NOG retired breeder mice aged 16-40 weeks. We established that the total incidence of lymphomas was only 0...
July 6, 2017: Experimental Animals
https://www.readbyqxmd.com/read/28677540/generation-of-non-transgenic-ips-cells-from-human-cord-blood-cd34-cells-under-animal-component-free-conditions
#7
Alexandra Haase, Gudrun Göhring, Ulrich Martin
Recently, many hurdles and limitations for production of clinically applicable iPSC derivatives have been overcome. Transgene-free iPSCs can be efficiently derived from easily accessible cell sources such as blood. Here we describe the generation of transgene-free hiPS cells from cord blood derived CD34(+) cells, reprogrammed using CytoTune™ Sendai reprogramming vectors. CD34(+) cell isolation, cultivation, reprogramming and establishment of resulting hiPSC lines were performed under the exclusive usage of animal-derived component-free (ADCF) materials and components...
May 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28677538/generation-of-a-sprague-dawley-gfp-rat-ips-cell-line
#8
Giulia Coppiello, Gloria Abizanda, Natalia Aguado, Elena Iglesias, Olalla Iglesias-Garcia, Antonio Lo Nigro, Felipe Prosper, Xabier L Aranguren
We generated a rat iPSC line called ATCi-rSD95 from transgenic Sprague-Dawley GFP fetal fibroblasts. Established ATCi-rSD95 cells present a normal karyotype, silencing of the transgenes and express pluripotency-associated markers. Additionally, ATCi-rSD95 cells are able to form teratoma with differentiated cells derived from the three germ-layers that maintain the GFP expression.
May 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28677534/generation-and-cardiac-subtype-specific-differentiation-of-pitx2-deficient-human-ips-cell-lines-for-exploring-familial-atrial-fibrillation
#9
Maike Marczenke, Jakob Fell, Ilaria Piccini, Albrecht Röpke, Guiscard Seebohm, Boris Greber
Loss-of-function mutations in the PITX2 transcription factor gene have been shown to cause familial atrial fibrillation (AF). To potentially model aspects of AF and unravel PITX2-regulated downstream genes for drug target discovery, we here report the generation of integration-free PITX2-deficient hiPS cell lines. We also show that both PITX2 knockout hiPS cells and isogenic wild-type controls can selectively be differentiated into human atrial cardiomyocytes, to potentially uncover differentially expressed gene sets between these groups...
May 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28677526/generation-of-macaca-fascicularis-ips-cell-line-atci-mf1-from-adult-skin-fibroblasts-using-non-integrative-sendai-viruses
#10
Giulia Coppiello, Gloria Abizanda, Natalia Aguado, Elena Iglesias, Estibaliz Arellano-Viera, Juan R Rodriguez-Madoz, Xonia Carvajal-Vergara, Felipe Prosper, Xabier L Aranguren
We generated ATCi-MF1 induced pluripotent stem (iPS) cell line from Macaca fascicularis adult skin fibroblasts using non-integrative Sendai viruses carrying OCT3/4, KLF4, SOX2 and c-MYC. Once established, ATCi-MF1 cells present a normal karyotype, are Sendai virus-free and express pluripotency associated markers. Microsatellite markers analysis confirmed the origin of the iPS cells from the parental fibroblasts. Pluripotency was tested with the in vivo teratoma formation assay. ATCi-MF1 cell line may be a useful primate iPS cell model to test different experimental conditions where the use of human cells can imply ethical issues, as microinjection of pluripotent stem cells in pre-implantational embryos...
May 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28674981/motoneuron-disease-basic-science
#11
Hristelina Ilieva, Nicholas J Maragakis
ALS is a relentless neurodegenerative disease in which motor neurons are the susceptible neuronal population. Their death results in progressive paresis of voluntary and respiratory muscles. The unprecedented rate of discoveries over the last two decades have broadened our knowledge of genetic causes and helped delineate molecular pathways. Here we critically review ALS epidemiology, genetics, pathogenic mechanisms, available animal models, and iPS cell technologies with a focus on their translational therapeutic potential...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28674456/pax2-is-dispensable-for-in-vitro-nephron-formation-from-human-induced-pluripotent-stem-cells
#12
Yusuke Kaku, Atsuhiro Taguchi, Shunsuke Tanigawa, Fahim Haque, Tetsushi Sakuma, Takashi Yamamoto, Ryuichi Nishinakamura
The kidney is formed by reciprocal interactions between the nephron progenitor and the ureteric bud, the former of which gives rise to the epithelia of nephrons consisting of glomeruli and renal tubules. The transcription factor PAX2 is essential for this mesenchymal-to-epithelial transition of nephron progenitors, as well as ureteric bud lineage development, in mice. PAX2 mutations in humans cause renal coloboma syndrome. We previously reported the induction of nephron progenitors and three-dimensional nephron structures from human induced pluripotent stem (iPS) cells...
July 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28673995/inhibition-of-acute-lethal-pulmonary-inflammation-by-the-ido-ahr-pathway
#13
Soung-Min Lee, Ha Young Park, Young-Sill Suh, Eun Hye Yoon, Juyang Kim, Won Hee Jang, Won-Sik Lee, Sae-Gwang Park, Il-Whan Choi, Inhak Choi, Sun-Woo Kang, Hwayoung Yun, Takanori Teshima, Byungsuk Kwon, Su-Kil Seo
The lung is a prototypic organ that was evolved to reduce immunopathology during the immune response to potentially hazardous endogenous and exogenous antigens. In this study, we show that donor CD4(+) T cells transiently induced expression of indoleamine 2,3-dioxygenase (IDO) in lung parenchyma in an IFN-γ-dependent manner early after allogeneic hematopoietic stem cell transplantation (HSCT). Abrogation of host IDO expression by deletion of the IDO gene or the IFN-γ gene in donor T cells or by FK506 treatment resulted in acute lethal pulmonary inflammation known as idiopathic pneumonia syndrome (IPS)...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28672915/induction-of-reprogramming-of-human-amniotic-epithelial-cells-into-ips-cells-by-overexpression-of-yap-oct4-and-sox2-through-the-activation-of-the-hippo-yap-pathway
#14
Yanhui Zhao, Xinfeng Fei, Jianming Guo, Gang Zou, Weidong Pan, Jingju Zhang, Yongyi Huang, Te Liu, Weiwei Cheng
The present study has reported a novel method for producing induced pluripotent stem (iPS) cells. Primary human amniotic epithelial cells (HuAECs) were isolated from the amniotic membranes of pregnant women who received Cesarean sections. These cells were infected with retroviruses carrying octamer-binding transcription factor 4 (Oct4), (sex determining region Y)-box 2 (Sox2) and Yes-associated protein (Yap) (OSY). Following in vitro culture for ~14 days, epithelial-like HuAECs exhibited several iPS clone-like cell colonies (OSY-iPS)...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28666145/simple-and-effective-generation-of-transgene-free-induced-pluripotent-stem-cells-using-an-auto-erasable-sendai-virus-vector-responding-to-microrna-302
#15
Ken Nishimura, Manami Ohtaka, Hitomi Takada, Akira Kurisaki, Nhi Vo Kieu Tran, Yen Thi Hai Tran, Koji Hisatake, Masayuki Sano, Mahito Nakanishi
Transgene-free induced pluripotent stem cells (iPSCs) are valuable for both basic research and potential clinical applications. We previously reported that a replication-defective and persistent Sendai virus (SeVdp) vector harboring four reprogramming factors (SeVdp-iPS) can efficiently induce generation of transgene-free iPSCs. This vector can express all four factors stably and simultaneously without chromosomal integration and can be eliminated completely from reprogrammed cells by suppressing vector-derived RNA-dependent RNA polymerase...
June 20, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28665994/a-novel-role-of-kr%C3%A3-ppel-like-factor-4-in-zhikong-scallop-chlamys-farreri-during-spermatogenesis
#16
Dandan Yang, Zhifeng Zhang, Shaoshuai Liang, Qiankun Yang, Yingrui Wang, Zhenkui Qin
Krüppel-like factor 4 (KLF4) is a kind of zinc finger transcription factor, which is involved in terminal differentiation of epithelial cells and reprogramming of somatic cells to induced pluripotent stem (iPS) cells in mammals. In the present study, we identified a full-length cDNA of Klf4 in Zhikong scallop Chamys farreri (Cf-Klf4) and found that Cf-Klf4 presented a sexual dimorphic expression characteristic in C. farreri gonads. Cf-Klf4 expression was significantly higher in testes than in ovaries from growing stage to mature stage detected by quantitative real-time PCR, and was located in male gametes, except for spermatozoa during spermatogenesis through in situ hybridization and immunohistochemistry, while no positive signal was visible in female gametes during oogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28661522/tubulogenesis-of-co-cultured-human-ips-derived-endothelial-cells-and-human-mesenchymal-stem-cells-in-fibrin-and-gelatin-methacrylate-gels
#17
G A Calderon, P Thai, C W Hsu, B Grigoryan, S M Gibson, M E Dickinson, J S Miller
Here, we investigate the tubulogenic potential of commercially-sourced iPS-ECs with and without supporting commercially-sourced hMSCs within 3D natural fibrin or semi-synthetic gelatin methacrylate (GelMA) hydrogels. We developed a selectable dual color third generation lentiviral reporter (hEF1α-H2B-mOrange2-IRES-EGFP PGK-Puro) to differentially label the nucleus and cytoplasm of iPS-ECs which allowed real-time tracking of key steps of vascular morphogenesis such as vacuole formation and coalescence to form shared multicellular lumens...
June 29, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28658972/programming-microphysiological-systems-for-children-s-health-protection
#18
T B Knudsen, B Klieforth, W Slikker
Microphysiological systems (MPS) and computer simulation models that recapitulate the underlying biology and toxicology of critical developmental transitions are emerging tools for developmental effects assessment of drugs/chemicals. Opportunities and challenges exist for their application to alternative, more public health relevant and efficient chemical toxicity testing methods. This is especially pertinent to children's health research and the evaluation of complex embryological and reproductive impacts of drug/chemical exposure...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28649446/phenotypic-profiling-of-cftr-modulators-in-patient-derived-respiratory-epithelia
#19
Saumel Ahmadi, Zoltan Bozoky, Michelle Di Paola, Sunny Xia, Canhui Li, Amy P Wong, Leigh Wellhauser, Steven V Molinski, Wan Ip, Hong Ouyang, Julie Avolio, Julie D Forman-Kay, Felix Ratjen, Jeremy A Hirota, Johanna Rommens, Janet Rossant, Tanja Gonska, Theo J Moraes, Christine E Bear
Pulmonary disease is the major cause of morbidity and mortality in patients with cystic fibrosis, a disease caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. Heterogeneity in CFTR genotype-phenotype relationships in affected individuals plus the escalation of drug discovery targeting specific mutations highlights the need to develop robust in vitro platforms with which to stratify therapeutic options using relevant tissue. Toward this goal, we adapted a fluorescence plate reader assay of apical CFTR-mediated chloride conductance to enable profiling of a panel of modulators on primary nasal epithelial cultures derived from patients bearing different CFTR mutations...
April 14, 2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/28649106/-aging-and-homeostasis-aging-control-through-cardiac-regenerative-medicine
#20
Katsuhisa Matsuura
Heart disease is one of the leading causes of death in the developed countries and various physical conditions in heart failure attribute to the impaired physical activities, which promotes aging. The principle cause of heart failure is the loss of self-renewal ability of cardiomyocytes in various injuries such as myocardial infarction. The replacement of injured tissues with the regenerated human myocardial tissues using technologies on tissue engineering and iPS cell will provide us the novel therapeutic strategy for heart failure and the related aging issues...
2017: Clinical Calcium
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