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https://www.readbyqxmd.com/read/29783088/evaluation-of-genotoxicity-and-mutagenic-effects-of-vector-dna-nanocomplexes-in-transfected-mesenchymal-stem-cells-by-flow-cytometry
#1
Alireza Nomani, Xuguang Chen, Arash Hatefi
In recent years, there has been a great deal of interest in ex-vivo genetic modification of mesenchymal stem cells (MSCs) to meet various biomedical needs. Considering the self-renewal potential of MSCs, it is critically important to ensure that transfection vectors (gene carriers) do not induce genotoxicity because they could theoretically turn a single stem cell into a cancer-initiating cell. Unfortunately, there is currently no reliable, unbiased, and quantitative method to measure genotoxicity (micronuclei formation) of gene carriers directly in transfected MSCs...
May 18, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29782871/neuralized1a-regulates-asymmetric-division-in-mouse-lewis-lung-carcinoma-cells
#2
Liangsheng Kong, Jingyuan Li, Yongli Liu, Zhiwei Sun, Shixia Zhou, Junling Tang, Ting Ye, Jianyu Wang, H Rosie Xing
Asymmetric division (ASD), the unique characteristic of normal stem cells, is regarded as a stemness marker when applied to the study of cancer stem cells (CSCs). However, the role of ASD in the self-renewal of CSCs and its regulation remain largely unknown. Here, we first established a mouse Lewis lung carcinoma CSC cell line that could undergo asymmetric division (LLC-ASD cells) derived from the parental mouse Lewis lung carcinoma cancer cells (LLC-Parental cells). In vitro assessment of stemness by RT-qPCR and western blot analysis of stem cell markers, clonogenic assay (p < 0...
May 18, 2018: Life Sciences
https://www.readbyqxmd.com/read/29782854/combined-treatment-with-sorafenib-and-silibinin-synergistically-targets-both-hcc-cells-and-cancer-stem-cells-by-enhanced-inhibition-of-the-phosphorylation-of-stat3-erk-akt
#3
Jie Mao, Hongbao Yang, Tingting Cui, Pan Pan, Nadia Kabir, Duo Chen, Jinyan Ma, Xingyi Chen, Yijun Chen, Yong Yang
Silibinin, a nontoxic bioactive component in milk thistle, is used as a liver-protective drug in the clinic mainly because of its antioxidant and anti-inflammation activities. In this study, we studied the cytotoxic effects of silibinin combined with sorafenib on hepatocellular carcinoma (HCC). The results indicated that silibinin combined with sorafenib potently inhibited the proliferation of various HCC cells and induced significant apoptosis. In an HCC subcutaneous transplantation tumor model, the combination of silibinin and sorafenib significantly suppressed tumor growth compared with monotherapy...
May 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29782008/de-novo-generation-of-somatic-stem-cells-by-yap-taz
#4
Tito Panciera, Luca Azzolin, Daniele Di Biagio, Antonio Totaro, Michelangelo Cordenonsi, Stefano Piccolo
Here we present protocols to isolate primary differentiated cells and turn them into stem/progenitor cells (SCs) of the same lineage by transient expression of the transcription factor YAP. With this method, luminal differentiated (LD) cells of the mouse mammary gland are converted into cells that exhibit molecular and functional properties of mammary SCs. YAP also turns fully differentiated pancreatic exocrine cells into pancreatic duct-like progenitors. Similarly, to endogenous, natural SCs, YAP-induced stem-like cells ("ySCs") can be eventually expanded as organoid cultures long term in vitro, without further need of ectopic YAP/TAZ, as ySCs are endowed with a heritable self-renewing SC-like state...
May 7, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29781034/specific-inhibitor-of-notch%C3%A2-3-enhances-the-sensitivity-of-nsclc-cells-to-gemcitabine
#5
Bi-Dan Hu, Jia Guo, Yuan-Zi Ye, Ting Du, Chun-Song Cheng, Qian Jiang, Ruo-Nan Liu, Yan-Bei Zhang
Notch‑3 is a receptor of the Notch signaling pathway and plays an important role in regulating self‑renewal, differentiation and apoptosis in cancer cells. Overexpression of Notch‑3 has been proved to be associated with resistance to gemcitabine (GEM) and poor patient prognosis for various malignant tumors. In the present study, two non‑small cell lung cancer (NSCLC) cell lines, H1299 and A549, were induced with GEM for two months and then were treated with various concentrations of a Notch signaling blocker, N‑[N‑(3,5‑difluorophenacetyl)‑L‑alanyl]‑S‑phenylglycine t‑butyl ester (DAPT), with the goal of reducing expression of Notch intracellular domain 3 (NICD3)...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29780813/loss-of-heterogeneity-quiescence-and-differentiation-in-muscle-stem-cells
#6
REVIEW
Haser Hasan Sutcu, Miria Ricchetti
Skeletal muscle stem cells in the adult display heterogeneity that has been functionally linked to their behavior, self-renewal capacity, and resistance to stress in hostile environments. Behavioral heterogeneity emerges also during developmental myogenesis. Muscle stem cell diversity may be functionally linked to the changing needs of skeletal muscle regeneration. Intriguingly, dramatic reduction of stem cell diversity, the "clonal drift", that implies loss of stem cells and related expansion of clonally related stem cells has been reported for tissue replacement in several adult tissues and suggested in the zebrafish embryo...
2018: Stem Cell Investigation
https://www.readbyqxmd.com/read/29780673/breast-fibroblasts-in-both-cancer-and-normal-tissues-induce-phenotypic-transformation-of-breast-cancer-stem-cells-a-preliminary-study
#7
Bixiao Wang, Chunfang Xi, Mingwei Liu, Haichen Sun, Shuang Liu, Lei Song, Hua Kang
Background: Breast cancer stem cells (BCSCs) are associated with the invasion of breast cancer. In recent years, studies have demonstrated different phenotypes among BCSCs. Furthermore, BCSCs of diverse phenotypes are present at different tumour sites and different histological stages. Fibroblasts are involved in the phenotypic transformation of BCSCs. Cancer-associated fibroblasts (CAFs) participate in the induction of epithelial-mesenchymal transition, thereby promoting the acquisition of stem cell characteristics, but little is known about the role of normal fibroblasts (NFs) in the phenotypic transformation of BCSCs or about the effect of CAFs and NFs on BCSC phenotypes...
2018: PeerJ
https://www.readbyqxmd.com/read/29780254/are-ovarian-cancer-stem-cells-the-target-for-innovative-immunotherapy
#8
REVIEW
Liang Wang, Tianmin Xu, Manhua Cui
Cancer stem cells (CSCs), a subpopulation of cancer cells with the ability of self-renewal and differentiation, are believed to be responsible for tumor generation, progression, metastasis, and relapse. Ovarian cancer, the most malignant gynecological cancer, has consistent pathology behavior with CSC model, which suggests that therapies based on ovarian cancer stem cells (OCSCs) can gain a more successful prognosis. Much evidence has proved that epigenetic mechanism played an important role in tumor formation and sustainment...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29779899/signaling-dependent-control-of-apical-membrane-size-and-self-renewal-in-rosette-stage-human-neuroepithelial-stem-cells
#9
Jan-Philip Medelnik, Kathleen Roensch, Satoshi Okawa, Antonio Del Sol, Osvaldo Chara, Levan Mchedlishvili, Elly M Tanaka
In the developing nervous system, neural stem cells are polarized and maintain an apical domain facing a central lumen. The presence of apical membrane is thought to have a profound influence on maintaining the stem cell state. With the onset of neurogenesis, cells lose their polarization, and the concomitant loss of the apical domain coincides with a loss of the stem cell identity. Little is known about the molecular signals controlling apical membrane size. Here, we use two neuroepithelial cell systems, one derived from regenerating axolotl spinal cord and the other from human embryonic stem cells, to identify a molecular signaling pathway initiated by lysophosphatidic acid that controls apical membrane size and consequently controls and maintains epithelial organization and lumen size in neuroepithelial rosettes...
May 10, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29779895/identification-and-single-cell-functional-characterization-of-an-endodermally-biased-pluripotent-substate-in-human-embryonic-stem-cells
#10
Thomas F Allison, Andrew J H Smith, Konstantinos Anastassiadis, Jackie Sloane-Stanley, Veronica Biga, Dylan Stavish, James Hackland, Shan Sabri, Justin Langerman, Mark Jones, Kathrin Plath, Daniel Coca, Ivana Barbaric, Paul Gokhale, Peter W Andrews
Human embryonic stem cells (hESCs) display substantial heterogeneity in gene expression, implying the existence of discrete substates within the stem cell compartment. To determine whether these substates impact fate decisions of hESCs we used a GFP reporter line to investigate the properties of fractions of putative undifferentiated cells defined by their differential expression of the endoderm transcription factor, GATA6, together with the hESC surface marker, SSEA3. By single-cell cloning, we confirmed that substates characterized by expression of GATA6 and SSEA3 include pluripotent stem cells capable of long-term self-renewal...
May 9, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29779894/epigenetic-regulation-by-baf-complexes-limits-neural-stem-cell-proliferation-by-suppressing-wnt-signaling-in-late-embryonic-development
#11
Huong Nguyen, Cemil Kerimoglu, Mehdi Pirouz, Linh Pham, Kamila A Kiszka, Godwin Sokpor, M Sadman Sakib, Joachim Rosenbusch, Ulrike Teichmann, Rho H Seong, Anastassia Stoykova, Andre Fischer, Jochen F Staiger, Tran Tuoc
During early cortical development, neural stem cells (NSCs) divide symmetrically to expand the progenitor pool, whereas, in later stages, NSCs divide asymmetrically to self-renew and produce other cell types. The timely switch from such proliferative to differentiative division critically determines progenitor and neuron numbers. However, the mechanisms that limit proliferative division in late cortical development are not fully understood. Here, we show that the BAF (mSWI/SNF) complexes restrict proliferative competence and promote neuronal differentiation in late corticogenesis...
May 8, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29778801/injury-and-stress-responses-of-adult-neural-crest-derived-cells
#12
REVIEW
Vadims Parfejevs, Ana T Antunes, Lukas Sommer
Multipotent neural crest cells can self-renew and give rise to a plethora of neural and non-neural cell types in the vertebrate embryo. Intriguingly, cells reminiscent of such neural crest stem cells (NCSCs) have also been isolated from various postnatal and adult neural crest (NC)-derived structures. However, it has been debated whether NCSC-like cells in the adult correspond to 'in vitro artefacts' emerging upon isolation or fulfil a physiological role in vivo. Here, we discuss recent findings indicating that in different adult NC derivatives, injury or stress responses induce a NCSC-like state, presumably by reprogramming of differentiated cells such as Schwann cells...
May 17, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29778568/lnctic1-interacts-with-%C3%AE-catenin-to-drive-liver-tic-self-renewal-and-liver-tumorigenesis
#13
Zhenzhen Chen, Lintong Yao, Yating Liu, Pingping Zhu
Liver tumor-initiating cells (TICs) are drivers of liver tumorigenesis, and Wnt/β-catenin activation plays a principal role in the self-renewal of liver TICs. Despite a deep understanding of Wnt/β-catenin regulation, the roles of long noncoding RNAs (lncRNAs) in Wnt/β-catenin activation and liver TIC self-renewal are largely unknown. Here, we performed unbiased screening of lncRNAs in liver tumorigenesis and found lncTIC1 was highly expressed with liver tumorigenesis. LncTIC1 was also highly expressed in liver TICs and required for the self-renewal of liver TICs...
May 17, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29776381/wnt-signaling-in-multiple-myeloma-a-central-player-in-disease-with-therapeutic-potential
#14
REVIEW
Ingrid Spaan, Reinier A Raymakers, Anja van de Stolpe, Victor Peperzak
Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow...
May 18, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29775782/network-based-expression-analyses-and-experimental-validations-revealed-high-co-expression-between-yap1-and-stem-cell-markers-compared-to-differentiated-cells
#15
Fariba Dehghanian, Zohreh Hojati, Fariba Esmaeili, Ali Masoudi-Nejad
The Hippo signaling pathway is identified as a potential regulatory pathway which plays critical roles in differentiation and stem cell self-renewal. Yap1 is a primary transcriptional effector of this pathway. The importance of Yap1 in embryonic stem cells (ESCs) and differentiation procedure remains a challenging question, since two different observations have been reported. To answer this question we used co-expression network and differential co-expression analyses followed by experimental validations. Our results indicate that Yap1 is highly co-expressed with stem cell markers in ESCs but not in differentiated cells (DCs)...
May 15, 2018: Genomics
https://www.readbyqxmd.com/read/29775615/extracellular-matrix-protein-dmp1-suppresses-osteogenic-differentiation-of-mesenchymal-stem-cells
#16
Shufan Zhang, Huixuan Wan, Peng Wang, Mengmeng Liu, Gongchen Li, Chunxue Zhang, Yao Sun
Mesenchymal Stem Cells (MSCs) are self-renewing and multipotent stem cells which was investigated for diverse clinical applications. However, complex mechanism of MSCs fate determination is still not fully disclosed. Extracellular matrix (ECM) proteins contribute to maintain MSCs stemness by providing extracellular microenvironment. Increasing evidences show that ECM proteins could also regulate the fate of MSCs directly. Dentin matrix protein 1 (DMP1) is an ECM protein enrich in bone tissue and terminal cells, which well-known in promoting osteoblasts and osteocytes maturation, and facilitate mineralization...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29774991/aggregate-mesenchymal-stem-cell-delivery-ameliorates-the-regenerative-niche-for-muscle-repair
#17
Marissa A Ruehle, Hazel Y Stevens, Aaron M Beedle, Robert E Guldberg, Jarrod A Call
Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease due to the absence of the dystrophin protein from the muscle cell membrane which renders the muscle susceptible to continuous damage. In DMD patients, muscle weakness, together with cycles of degeneration/regeneration and replacement with non-contractile tissue, limit mobility and lifespan. Since the loss of dystrophin result in loss of polarity and a reduction in the number of self-renewing satellite cells, it is postulated that these patients could achieve an improved quality of life if delivered cells could restore satellite cell function...
May 18, 2018: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29773872/computational-identification-of-specific-genes-for-glioblastoma-stem-like-cells-identity
#18
Giulia Fiscon, Federica Conte, Valerio Licursi, Sergio Nasi, Paola Paci
Glioblastoma, the most malignant brain cancer, contains self-renewing, stem-like cells that sustain tumor growth and therapeutic resistance. Identifying genes promoting stem-like cell differentiation might unveil targets for novel treatments. To detect them, here we apply SWIM - a software able to unveil genes (named switch genes) involved in drastic changes of cell phenotype - to public datasets of gene expression profiles from human glioblastoma cells. By analyzing matched pairs of stem-like and differentiated glioblastoma cells, SWIM identified 336 switch genes, potentially involved in the transition from stem-like to differentiated state...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29772932/recent-advances-in-kartogenin-for-cartilage-regeneration
#19
Gaorui Cai, Wei Liu, Yong He, Jianghong Huang, Li Duan, Jianyi Xiong, Lijun Liu, Daping Wang
Either osteoarthritisor sports-related injuries can lead to cartilage defects,whereas both chondrocyte self-renewal and conventional treatments face limitations. In cartilage regenerative medicine, growth factors are commonly used to induce chondrogenic differentiation of stem cells. However, application of growth factors is confined by some drawbacks. Emerging small molecules are regarded as an alternative for cartilage regeneration. A recently discovered small-molecule compound, kartogenin (KGN), has been proven to be a chondrogenic and chondroprotective agent and is more effective in inducing cartilage regeneration when compared with growth factors...
May 18, 2018: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29771420/imp3-promotes-tnbc-stem-cell-property-through-mirna-34a-regulation
#20
Q-D Huang, S-R Zheng, Y-J Cai, D-L Chen, Y-Y Shen, C-Q Lin, X-Q Hu, X-H Wang, H Shi, G-L Guo
OBJECTIVE: To explore the expression and function of insulin-like growth factor II (IGFII) mRNA binding protein (IMP3) in the Triple Negative Breast Cancer (TNBC). MATERIALS AND METHODS: According to previously reported gene expression array, we found that IMP3 had significantly higher expression in the CD44+CD24-ESA+ cell cluster, tumor initiating cell or cancer stem cell (CSCs), compared to other tumor cells. Based on the GEO database (GEO accession No. GSE6883), we detected the mRNA levels of IMP 1,2 and 3 by quantitative polymerase chain reaction (q-PCR) in CD44+CD24-ESA+ cell cluster and other breast tumor cell clusters...
May 2018: European Review for Medical and Pharmacological Sciences
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