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Stem Cells

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https://www.readbyqxmd.com/read/28710827/comparison-of-non-coding-rnas-in-exosomes-and-functional-efficacy-of-human-embryonic-stem-cell-versus-induced-pluripotent-stem-cell-derived-cardiomyocytes
#1
Won Hee Lee, Wenyi Chen, Ning-Yi Shao, Dan Xiao, Xulei Qin, Natalie Baker, Hye Ryeong Michelle Bae, Praveen Shukla, Haodi Wu, Kazuki Kodo, Sang-Ging Ong, Joseph C Wu
BACKGROUND: Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can serve as unlimited cell sources for cardiac regenerative therapy. However, the functional equivalency between human ESC-CMs and iPSC-CMs for cardiac regenerative therapy has not been demonstrated. Here we performed a head-to-head comparison of ESC-CMs and iPSC-CMs in their ability to restore cardiac function in a rat myocardial infarction (MI) model as well as their exosomal secretome...
July 14, 2017: Stem Cells
https://www.readbyqxmd.com/read/28699252/mesenchymal-stromal-cell-derived-il-6-promotes-epithelial-mesenchymal-transition-and-acquisition-of-epithelial-stem-like-cell-properties-in-ameloblastoma-epithelial-cells
#2
Chunmiao Jiang, Qunzhou Zhang, Rabie M Shanti, Shihong Shi, Ting-Han Chang, Lee Carrasco, Faizan Alawi, Anh D Le
Epithelial-mesenchymal transition (EMT), a biological process associated with cancer stem-like or cancer-initiating cell (CSC) formation, contributes to the invasiveness, metastasis, drug resistance, and recurrence of the malignant tumors; it remains to be determined whether similar processes contribute to the pathogenesis and progression of ameloblastoma, a benign but locally invasive odontogenic neoplasm. Here, we demonstrated that EMT- and stem cell-related genes were expressed in the epithelial islands of the most common histologic variant subtype, the follicular ameloblastoma...
July 11, 2017: Stem Cells
https://www.readbyqxmd.com/read/28699232/acetylated-stat3-functions-as-molecular-adaptor-independent-of-transcriptional-activity-during-human-cardiogenesis
#3
Ashish Mehta, Chrishan J A Ramachandra, Anuja Chitre, Pritpal Singh, Chong Hui Lua, Winston Shim
Activation of signal transducer and activator of transcription 3 (STAT3) is imperative for mammalian development, specifically cardiogenesis. STAT3 phosphorylation and acetylation are key post-translational modifications that regulate its transcriptional activity. Significance of such modifications during human cardiogenesis remains elusive. Using human pluripotent stem cells (hPSCs) to recapitulate cardiogenesis, two independently modified STAT3α (92kDa) isoforms (phosphorylated and acetylated), which perform divergent functions were identified during cardiomyocyte formation...
July 11, 2017: Stem Cells
https://www.readbyqxmd.com/read/28699179/colorectal-cancer-stem-cells-acquire-chemoresistance-through-the-upregulation-of-fbxw7-and-the-consequent-degradation-of-c-myc
#4
Daisuke Izumi, Takatsugu Ishimoto, Keisuke Miyake, Tsugio Eto, Kota Arima, Yuki Kiyozumi, Tomoyuki Uchihara, Junji Kurashige, Masaaki Iwatsuki, Yoshifumi Baba, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Masayuki Watanabe, Ajay Goel, Patrick Tan, Hideo Baba
The cancer stem cell (CSC) paradigm suggests that tumors are organized hierarchically. We previously established an LGR5(+) human colorectal cancer stem-cell-enriched cell line (colorectal CSCs) that expresses well-accepted colorectal CSC markers and that can dynamically switch between proliferative and drug-resistant non-cycling states. We performed this study to elucidate the molecular mechanisms responsible for evading cell death in colorectal CSCs mediated by anticancer agents. During the cell cycle arrest caused by anticancer agents, we found that c-Myc expression was substantially decreased in colorectal CSCs...
July 11, 2017: Stem Cells
https://www.readbyqxmd.com/read/28639375/challenges-in-regenerating-the-diabetic-heart-a-comprehensive-review
#5
REVIEW
Venkata R Satthenapalli, Regis R Lamberts, Rajesh Katare
Stem cell therapy is one of the promising regenerative strategies developed to improve cardiac function in patients with ischemic heart diseases (IHD). However, this approach is limited in IHD patients with diabetes due to a progressive decline in the regenerative capacity of stem cells. This decline is mainly attributed to the metabolic memory incurred by diabetes on stem cell niche and their systemic cues. Understanding the molecular pathways involved in the diabetes-induced deterioration of stem cell function will be critical for developing new cardiac regeneration therapies...
June 22, 2017: Stem Cells
https://www.readbyqxmd.com/read/28631381/tec-controls-pluripotency-and-early-cell-fate-decisions-of-human-pluripotent-stem-cells-via-regulation-of-fgf2-secretion
#6
Tereza Vanova, Zaneta Konecna, Zuzana Zbonakova, Giuseppe La Venuta, Karolina Zoufalova, Sarka Jelinkova, Miroslav Varecha, Vladimir Rotrekl, Pavel Krejci, Walter Nickel, Petr Dvorak, Michaela Kunova Bosakova
Human pluripotent stem cells (hPSC) require signaling provided by fibroblast growth factor (FGF) receptors. This can be initiated by the recombinant FGF2 ligand supplied exogenously, but hPSC further support their niche by secretion of endogenous FGF2. In this study, we describe a role of TEC kinase (tyrosine kinase expressed in hepatocellular carcinoma) in this process. We show that TEC-mediated FGF2 secretion is essential for hPSC self-renewal, and its lack mediates specific differentiation. Following both shRNA- and siRNA-mediated TEC knock-down, hPSC secrete less FGF2...
June 20, 2017: Stem Cells
https://www.readbyqxmd.com/read/28600830/brief-report-external-beam-radiation-therapy-for-the-treatment-of-human-pluripotent-stem-cell-derived-teratomas
#7
Andrew S Lee, Chad Tang, Wan Xing Hong, Sujin Park, Magdalena Bazalova-Carter, Geoff Nelson, Veronica Sanchez-Freire, Isaac Bakerman, Wendy Zhang, Evgenios Neofytou, Andrew J Connolly, Charles K Chan, Edward E Graves, Irving L Weissman, Patricia K Nguyen, Joseph C Wu
Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced PSCs (hiPSCs), have great potential as an unlimited donor source for cell-based therapeutics. The risk of teratoma formation from residual undifferentiated cells, however, remains a critical barrier to the clinical application of these cells. Herein, we describe external beam radiation therapy (EBRT) as an attractive option for the treatment of this iatrogenic growth. We present evidence that EBRT is effective in arresting growth of hESC-derived teratomas in vivo at day 28 post-implantation by using a microCT irradiator capable of targeted treatment in small animals...
June 10, 2017: Stem Cells
https://www.readbyqxmd.com/read/28600828/allogeneic-mscs-and-recycled-autologous-chondrons-mixed-in-a-one-stage-cartilage-cell-transplantion-a-first-in-man-trial-in-35-patients
#8
Tommy S de Windt, Lucienne A Vonk, Ineke C M Slaper-Cortenbach, Razmara Nizak, Mattie H P van Rijen, Daniel B F Saris
MSCs are known as multipotent mesenchymal stem cells that have been found capable of differentiating into various lineages including cartilage. However, recent studies suggest MSCs are pericytes that stimulate tissue repair through trophic signaling. Aimed at articular cartilage repair in a one-stage cell transplantation, this study provides first clinical evidence that MSCs stimulate autologous cartilage repair in the knee without engrafting in the host tissue. A phase I (first-in-man) clinical trial studied the one-stage application of allogeneic MSCs mixed with 10% or 20% recycled defect derived autologous chondrons for the treatment of cartilage defects in 35 patients...
June 10, 2017: Stem Cells
https://www.readbyqxmd.com/read/28600817/il17a-dependent-asymmetric-stem-cell-divisions-are-increased-in-human-psoriasis-a-mechanism-underlying-benign-hyperproliferation
#9
Alexandra Charruyer, Stephen Fong, Giselle Vitcov, Samuel Sklar, Leah Tabernik, Monica Taneja, Melinda Caputo, Catherine Soeung, Lili Yue, Yoshi Uchida, Sarah T Arron, Karen Horton, Robert Foster, Shigetoshi Sano, Jeffrey North, Ruby Ghadially
The balance between asymmetric and symmetric stem cell (SC) divisions is key to tissue homeostasis and dysregulation of this balance has been shown in cancers. We hypothesized that the balance between asymmetric SC divisions (ACDs) and symmetric cell divisions (SCDs) would be dysregulated in the benign hyperproliferation of psoriasis. We found that, whereas SCDs were increased in squamous cell carcinoma (SCC) (human and murine), ACDs were increased in the benign hyperproliferation of psoriasis (human and murine)...
June 10, 2017: Stem Cells
https://www.readbyqxmd.com/read/28600813/elucidation-of-altered-pathways-in-tumor-initiating-cells-of-triple-negative-breast-cancer-a-useful-cell-model-system-for-drug-screening
#10
Anne G Christensen, Sidse Ehmsen, Mikkel G Terp, Richa Batra, Nicolas Alcaraz, Jan Baumbach, Julie B Noer, José Moreira, Rikke Leth-Larsen, Martin R Larsen, Henrik J Ditzel
A limited number of cancer cells within a tumor are thought to have self-renewing and tumor-initiating capabilities that produce the remaining cancer cells in a heterogeneous tumor mass. Elucidation of central pathways preferentially used by tumor-initiating cells/cancer stem cells (CSCs) may allow their exploitation as potential cancer therapy targets. We used single cell cloning to isolate and characterize four isogenic cell clones from a triple-negative breast cancer cell line; two exhibited mesenchymal-like and two epithelial-like characteristics...
June 10, 2017: Stem Cells
https://www.readbyqxmd.com/read/28589621/concise-review-mesenchymal-stem-cells-in-neurodegenerative-diseases
#11
REVIEW
Rotem Volkman, Daniel Offen
Stem cell-based therapies for neurodegenerative diseases aim at halting clinical deterioration by regeneration and by providing local support for damaged tissue. Mesenchymal stem cells (MSCs) hold great potential for cell therapy as they can be efficiently derived from adult tissue, ex vivo expanded in culture and safely transplanted autologously. MSCs were also shown to be able to differentiate towards neural fates and to secrete a broad range of factors able to promote nervous tissue maintenance and repair...
June 7, 2017: Stem Cells
https://www.readbyqxmd.com/read/28589555/common-and-distinctive-functions-of-the-hippo-effectors-taz-and-yap-in-skeletal-muscle-stem-cell-function
#12
Congshan Sun, Vanessa De Mello, Abdalla Mohamed, Huascar P Ortuste Quiroga, Amaya Garcia-Munoz, Abdullah Al Bloshi, Annie M Tremblay, Alexander von Kriegsheim, Elaina Collie-Duguid, Neil Vargesson, David Matallanas, Henning Wackerhage, Peter S Zammit
Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analyzed Taz in vivo and ex vivo in comparison with Yap. Small interfering RNA knockdown or retroviral-mediated expression of wild-type human or constitutively active TAZ mutants in satellite cells showed that TAZ promoted proliferation, a function shared with YAP. However, at later stages of myogenesis, TAZ also enhanced myogenic differentiation of myoblasts, whereas YAP inhibits such differentiation...
June 7, 2017: Stem Cells
https://www.readbyqxmd.com/read/28580685/yy1-expression-is-sufficient-for-the-maintenance-of-cardiac-progenitor-cell-state
#13
Serge Gregoire, Guang Li, Anthony C Sturzu, Robert J Schwartz, Sean M Wu
During cardiac development, DNA binding transcription factors and epigenetic modifiers regulate gene expression in cardiac progenitor cells (CPCs). We have previously shown that YY1 is essential for the commitment of mesodermal precursors into CPCs. However, the role of YY1 in the maintenance of CPC phenotype and their differentiation into cardiomyocytes is unknown. In this study, we found, by genome-wide transcriptional profiling and phenotypic assays, that YY1 overexpression prevents cardiomyogenic differentiation and maintains the proliferative capacity of CPCs...
June 5, 2017: Stem Cells
https://www.readbyqxmd.com/read/28580639/mesenchymal-stem-cells-stabilize-axonal-transports-for-autophagic-clearance-of-%C3%AE-synuclein-in-parkinsonian-models
#14
Se Hee Oh, Seok Cheol Lee, Dong Yeol Kim, Ha Na Kim, Jin Young Shin, Byoung Seok Ye, Phil Hyu Lee
Genome-wide association studies have identified two loci, SNCA and the microtubule (MT)-associated protein tau, as common risk factors for Parkinson's disease (PD). Specifically, α-synuclein directly destabilizes MT via tau phosphorylation and induces axonal transport deficits that are the primary events leading to an abnormal accumulation of α-synuclein that causes nigral dopaminergic cell loss. In the present study, we demonstrated that mesenchymal stem cells (MSCs) could modulate cytoskeletal networks and trafficking to exert neuroprotective properties in wild-type or A53T α-synuclein overexpressing cells and mice...
June 5, 2017: Stem Cells
https://www.readbyqxmd.com/read/28577307/disrupting-interactions-between-%C3%AE-catenin-and-activating-tcfs-reconstitutes-ground-state-pluripotency-in-mouse-embryonic-stem-cells
#15
Abil Saj, Sujash S Chatterjee, Bowen Zhu, Engin Cukuroglu, Tenzin Gocha, Xiaoqian Zhang, Jonathan Göke, Ramanuj DasGupta
The 2i-media, composed of two small molecule inhibitors (PD0325901 and CHIR99021) against MEK and GSK3-kinases, respectively, is known to establish naïve ground state pluripotency in mouse embryonic stem cells (mESCs). These inhibitors block MEK-mediated differentiation, while driving β-catenin dependent de-repression of pluripotency promoting targets. However, accumulating evidence suggest that β-catenin's association with activating TCFs (TCF7 and TCF7L2) can induce expression of several lineage-specific prodifferentiation genes...
June 2, 2017: Stem Cells
https://www.readbyqxmd.com/read/28577303/hhex-regulates-hematopoietic-stem-cell-self-renewal-and-stress-hematopoiesis-via-repression-of-cdkn2a
#16
Jacob T Jackson, Benjamin J Shields, Wei Shi, Ladina Di Rago, Donald Metcalf, Nicos A Nicola, Matthew P McCormack
The hematopoietically expressed homeobox transcription factor (Hhex) is important for the maturation of definitive hematopoietic progenitors and B-cells during development. We have recently shown that in adult hematopoiesis, Hhex is dispensable for maintenance of hematopoietic stem cells (HSCs) and myeloid lineages but essential for the commitment of common lymphoid progenitors (CLPs) to lymphoid lineages. Here, we show that during serial bone marrow transplantation, Hhex-deleted HSCs are progressively lost, revealing an intrinsic defect in HSC self-renewal...
June 2, 2017: Stem Cells
https://www.readbyqxmd.com/read/28577302/ip6k1-reduces-mesenchymal-stem-stromal-cell-fitness-and-potentiates-high-fat-diet-induced-skeletal-involution
#17
Siddaraju V Boregowda, Sarbani Ghoshal, Cori N Booker, Veena Krishnappa, Anutosh Chakraborty, Donald G Phinney
Mesenchymal stem/stromal cells (MSCs) are the predominant source of bone and adipose tissue in adult bone marrow and play a critical role in skeletal homeostasis. Age-induced changes in bone marrow favor adipogenesis over osteogenesis leading to skeletal involution and increased marrow adiposity so pathways that prevent MSC aging are potential therapeutic targets for treating age-related bone diseases. Here, we show that inositol hexakisphosphate kinase 1 (Ip6k1) deletion in mice increases MSC yields from marrow and enhances cell growth and survival ex vivo...
June 2, 2017: Stem Cells
https://www.readbyqxmd.com/read/28577296/criteria-for-chamber-specific-categorisation-of-human-cardiac-myocytes-derived-from-pluripotent-stem-cells
#18
REVIEW
Christopher Kane, Cesare M Terracciano
Human pluripotent stem cell-derived cardiomyocytes (PSC-CMs) have great potential application in almost all areas of cardiovascular research. A current major goal of the field is to build on the past success of differentiation strategies to produce cardiomyocytes with the properties of those originating from the different chambers of the adult human heart. With no anatomical origin or developmental pathway to draw on, the question of how to judge the success of such approaches and assess the chamber specificity of PSC-CMs has become increasingly important; commonly used methods have substantial limitations and are based on limited evidence to form such an assessment...
June 2, 2017: Stem Cells
https://www.readbyqxmd.com/read/28544378/concise-review-induced-pluripotent-stem-cell-based-drug-discovery-for-mitochondrial-disease
#19
REVIEW
Gizem Inak, Carmen Lorenz, Pawel Lisowski, Annika Zink, Barbara Mlody, Alessandro Prigione
High attrition rates and loss of capital plague the drug discovery process. This is particularly evident for mitochondrial disease that typically involves neurological manifestations and is caused by nuclear or mitochondrial DNA defects. This group of heterogeneous disorders is difficult to target because of the variability of the symptoms among individual patients and the lack of viable modeling systems. The use of induced pluripotent stem cells (iPSCs) might significantly improve the search for effective therapies for mitochondrial disease...
May 22, 2017: Stem Cells
https://www.readbyqxmd.com/read/28543863/prmt8-controls-the-pluripotency-and-mesodermal-fate-of-human-embryonic-stem-cells-by-enhancing-the-pi3k-akt-sox2-axis
#20
Ho-Chang Jeong, Soon-Jung Park, Jong-Jin Choi, Young-Hyun Go, Soon-Ki Hong, Ok-Seon Kwon, Joong-Gon Shin, Rae-Kwon Kim, Mi-Ok Lee, Su-Jae Lee, Hyoung Doo Shin, Sung-Hwan Moon, Hyuk-Jin Cha
Basic fibroblast growth factor (bFGF) supplementation is critical to maintain the pluripotency of human pluripotent stem cells (hPSCs) through activation of PI3K/AKT, rather than MEK/ERK pathway. Thus, elaborate molecular mechanisms that preserve PI3K/AKT signaling upon bFGF stimulation may exist in hPSCs. Protein arginine methyltransferase 8 (PRMT8) was expressed and then its level gradually decreased during spontaneous differentiation of human embryonic stem cells (hESCs). PRMT8 loss- or gain-of-function studies demonstrated that PRMT8 contributed to longer maintenance of hESC pluripotency, even under bFGF-deprived conditions...
May 20, 2017: Stem Cells
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