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Stem Cells

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https://www.readbyqxmd.com/read/28801931/immunomodulatory-effects-of-adipose-stromal-vascular-fraction-cells-promote-alternative-activation-macrophages-to-repair-tissue-damage
#1
Annie C Bowles, Rachel M Wise, Brittany Y Gerstein, Robert C Thomas, Roberto Ogelman, Isabella Febbo, Bruce A Bunnell
The pathogenesis of many diseases is driven by the interactions between helper T (TH ) cells and macrophages. The phenotypes of these cells are a functional dichotomy that are persuaded according to the surrounding milieu. In both multiple sclerosis (MS) and the experimental autoimmune encephalomyelitis (EAE) model, TH 1 and TH 17 cells propagate autoimmune signaling and inflammation in the peripheral lymphoid tissues. In turn, this pro-inflammatory repertoire promotes the classical activation, formerly the M1-type, macrophages...
August 12, 2017: Stem Cells
https://www.readbyqxmd.com/read/28795454/the-tcf7l2-pgc1%C3%AE-axis-connects-mitochondrial-biogenesis-and-metabolic-shift-with-stem-cell-commitment-to-hepatic-differentiation
#2
Anaïs Wanet, Marino Caruso, Jean-Baka Domelevo Entfellner, Mehdi Najar, Antoine Fattaccioli, Catherine Demazy, Jonathan Evraerts, Hoda El-Kehdy, Guillaume Pourcher, Etienne Sokal, Thierry Arnould, Nicki Tiffin, Mustapha Najimi, Patricia Renard
Increasing evidence supports that modifications in the mitochondrial content, oxidative phosphorylation (OXPHOS) activity, and cell metabolism influence the fate of stem cells. However, the regulators involved in the crosstalk between mitochondria and stem cell fate remain poorly characterized. Here, we identified a transcriptional regulatory axis, composed of TCF7L2 (transcription factor 7 like 2, a downstream effector of the Wnt/β-catenin pathway, repressed during differentiation) and PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1 alpha, the master regulator of mitochondrial biogenesis, induced during differentiation), coupling the loss of pluripotency and early commitment to differentiation, to the initiation of mitochondrial biogenesis and metabolic shift toward OXPHOS...
August 10, 2017: Stem Cells
https://www.readbyqxmd.com/read/28792678/modeling-glaucoma-retinal-ganglion-cells-generated-from-induced-pluripotent-stem-cells-of-patients-with-six6-risk-allele-show-developmental-abnormalities
#3
Pooja Teotia, Matthew J Van Hook, Christopher S Wichman, R Rand Allingham, Michael A Hauser, Iqbal Ahmad
Glaucoma represents a group of multifactorial diseases with a unifying pathology of progressive retinal ganglion cell (RGC) degeneration, causing irreversible vision loss. To test the hypothesis that RGCs are intrinsically vulnerable in glaucoma we have developed an in vitro model using the SIX6 risk allele carrying glaucoma patient-specific induced pluripotent stem cells (iPSCs) for generating functional RGCs. Here, we demonstrate that the efficiency of RGC generation by SIX6 risk allele iPSCs is significantly lower than iPSCs-derived from healthy, age-and sex-matched controls...
August 9, 2017: Stem Cells
https://www.readbyqxmd.com/read/28782268/reprogramming-antagonizes-the-oncogenicity-of-hoxa13-long-noncoding-rna-hottip-axis-in-gastric-cancer-cells
#4
Deng-Chyang Wu, Sophie S W Wang, Chung-Jung Liu, Kenly Wuputra, Kohsuke Kato, Yen-Liang Lee, Ying-Chu Lin, Ming-Ho Tsai, Chia-Chen Ku, Wen-Hsin Lin, Shin-Wei Wang, Shotaro Kishikawa, Michiya Noguchi, Chu-Chieh Wu, Yi-Ting Chen, Chee-Yin Chai, Chen-Lung Steve Lin, Kung-Kai Kuo, Ya-Han Yang, Hiroyuki Miyoshi, Yukio Nakamura, Shigeo Saito, Kyosuke Nagata, Chang-Shen Lin, Kazunari K Yokoyama
Reprogramming of cancer cells into induced pluripotent stem (iPSCs) is a compelling idea for inhibiting oncogenesis, especially through modulation of homeobox proteins in this reprogramming process. We examined the role of various long noncoding RNAs (lncRNAs)-homeobox protein HOXA13 axis on the switching of the oncogenic function of bone morphogenetic protein 7 (BMP7), which is significantly lost in the gastric cancer cell derived iPS-like cells (iPSLCs). BMP promoter activation occurred through the corecruitment of HOXA13, mixed-lineage leukemia 1 lysine N-methyltransferase (MLL1), WD repeat-containing protein 5 (WDR5), and lncRNA HoxA transcript at the distal tip (HOTTIP) to commit the epigenetic changes to the trimethylation of lysine 4 on histone H3 in cancer cells...
August 7, 2017: Stem Cells
https://www.readbyqxmd.com/read/28762569/gabp%C3%AE-is-involved-in-the-survival-of-mouse-embryonic-stem-cells
#5
Atsushi Ueda, Tadayuki Akagi, Takashi Yokota
Ets-related transcription factor GA-binding protein alpha (GABPα), which is encoded by Gabpa, is expressed in a variety of cell types and is involved in cellular functions such as cell cycle regulation, apoptosis, and differentiation. Here we generated Gabpa conditional knockout embryonic stem (ES) cells and characterized its cellular phenotypes. Disruption of Gabpa revealed that the proliferation of Gabpa-null ES cells was drastically repressed and cells started to die within 2 days. The repressed proliferation of Gabpa-null ES cells was recovered by artificially forced expression of GABPα...
August 1, 2017: Stem Cells
https://www.readbyqxmd.com/read/28758360/essential-roles-of-thyroid-hormone-regulated-hyaluronan-cd44-signaling-in-adult-stem-cell-development-during-xenopus-laevis-intestinal-remodeling
#6
Takashi Hasebe, Kenta Fujimoto, Mitsuko Kajita, Atsuko Ishizuya-Oka
In the amphibian intestine during metamorphosis, thyroid hormone (TH) induces some larval epithelial cells to dedifferentiate into stem cells, which generate the adult epithelium analogous to the mammalian intestinal epithelium. We have previously shown that the canonical Wnt signaling pathway is involved in adult epithelial development in the Xenopus laevis intestine. To understand the function of this pathway more precisely, we here focused on CD44, a major Wnt target, which has been identified as a TH response gene in the X...
July 31, 2017: Stem Cells
https://www.readbyqxmd.com/read/28758321/therapeutic-effect-of-human-adipose-tissue-derived-mesenchymal-stem-cells-in-experimental-corneal-failure-due-to-limbal-stem-cell-niche-damage
#7
Sara Galindo, José M Herreras, Marina López-Paniagua, Esther Rey, Ana de la Mata, María Plata-Cordero, Margarita Calonge, Teresa Nieto-Miguel
Limbal stem cells are responsible for the continuous renewal of the corneal epithelium. The destruction or dysfunction of these stem cells or their niche induces limbal stem cell deficiency (LSCD) leading to visual loss, chronic pain, and inflammation of the ocular surface. To restore the ocular surface in cases of bilateral LSCD, an extraocular source of stem cells is needed to avoid dependence on allogeneic limbal stem cells that are difficult to obtain, isolate, and culture. The aim of this work was to test the tolerance and the efficacy of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) to regenerate the ocular surface in two experimental models of LSCD that closely resemble the different severity grades of the human pathology...
July 31, 2017: Stem Cells
https://www.readbyqxmd.com/read/28758276/brief-report-human-acute-myeloid-leukemia-reprograming-to-pluripotency-is-a-rare-event-and-selects-for-patient-hematopoietic-cells-devoid-of-leukemic-mutations
#8
Jong-Hee Lee, Kyle R Salci, Jennifer C Reid, Luca Orlando, Borko Tanasijevic, Zoya Shapovalova, Mickie Bhatia
Induced pluripotent stem cell reprogramming has provided critical insights into disease processes by modeling the genetics and related clinical pathophysiology. Human cancer represents highly diverse genetics, as well as inter- and intra-patient heterogeneity, where cellular model systems capable of capturing this disease complexity would be invaluable. Acute myeloid leukemia (AML) represents one of most heterogeneous cancers and has been divided into genetic subtypes correlated with unique risk stratification over the decades...
July 31, 2017: Stem Cells
https://www.readbyqxmd.com/read/28748596/concise-review-stem-cells-for-corneal-wound-healing
#9
REVIEW
Mehrnoosh Saghizadeh, Andrei A Kramerov, Clive N Svendsen, Alexander V Ljubimov
Corneal wound healing is a complex process that occurs in response to various injuries and commonly used refractive surgery. It is a significant clinical problem, which may lead to serious complications due to either incomplete (epithelial) or excessive (stromal) healing. Epithelial stem cells clearly play a role in this process, whereas the contribution of stromal and endothelial progenitors is less well studied. The available evidence on stem cell participation in corneal wound healing is reviewed, together with the data on the use of corneal and non-corneal stem cells to facilitate this process in diseased or postsurgical conditions...
July 26, 2017: Stem Cells
https://www.readbyqxmd.com/read/28741855/in-vivo-rescue-of-the-hematopoietic-niche-by-pluripotent-stem-cell-complementation-of-defective-osteoblast-compartments
#10
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 cells (ESCs) and induced PSCs (iPSC), 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 used 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/28733998/quiescent-oct4-neural-stem-cells-nscs-repopulate-ablated-glial-fibrillary-acidic-protein-nscs-in-the-adult-mouse-brain
#11
Rachel L Reeve, Samantha Z Yammine, Cindi M Morshead, Derek van der Kooy
Adult primitive neural stem cells (pNSCs) are a rare population of glial fibrillary acidic protein (GFAP)(-) Oct4(+) cells in the mouse forebrain subependymal zone bordering the lateral ventricles that give rise to clonal neurospheres in leukemia inhibitory factor in vitro. pNSC neurospheres can be passaged to self-renew or give rise to GFAP(+) NSCs that form neurospheres in epidermal growth factor and fibroblast growth factor 2, which we collectively refer to as definitive NSCs (dNSCs). Label retention experiments using doxycycline-inducible histone-2B (H2B)-green fluorescent protein (GFP) mice and several chase periods of up to 1 year quantified the adult pNSC cell cycle time as 3-5 months...
July 21, 2017: Stem Cells
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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/28544378/concise-review-induced-pluripotent-stem-cell-based-drug-discovery-for-mitochondrial-disease
#18
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/28600830/brief-report-external-beam-radiation-therapy-for-the-treatment-of-human-pluripotent-stem-cell-derived-teratomas
#19
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...
August 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
#20
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...
August 2017: Stem Cells
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