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Stem Cells

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https://www.readbyqxmd.com/read/28544378/concise-review-induced-pluripotent-stem-cell-based-drug-discovery-for-mitochondrial-disease
#1
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
#2
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 methyltransferases 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
https://www.readbyqxmd.com/read/28520232/human-ipsc-msc-derived-xenografts-modulate-immune-responses-by-inhibiting-the-cleavage-of-caspases
#3
Cheng-Lin Li, Yun Leng, Bin Zhao, Chang Gao, Fei-Fei Du, Ning Jin, Qi-Zhou Lian, Shuang-Yue Xu, Guo-Liang Yan, Jun-Jie Xia, Guo-Hong Zhuang, Qing-Ling Fu, Zhong-Quan Qi
Mesenchymal stem cells (MSCs) negatively modulate immune properties. Induced pluripotent stem cells (iPSCs)-derived MSCs are alternative source of MSCs. However, the effects of iPSC-MSCs on T cells phenotypes in vivo remain unclear. We established an iPSC-MSC-transplanted host versus graft reaction mouse model using subcapsular kidney injection. Th1, Th2, regulatory T cells (Treg), and Th17 phenotypes and their cytokines were investigated in vivo and in vitro. The role of caspases and the soluble factors involved in the effects of MSCs were examined...
May 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28514506/human-adipose-derived-mesenchymal-stem-cell-secreted-cxcl1-and-cxcl8-facilitate-breast-tumor-growth-by-promoting-angiogenesis
#4
Yuan Wang, Junli Liu, Qingyuan Jiang, Jie Deng, Fen Xu, Xiaolei Chen, Fuyi Cheng, Yujing Zhang, Yunqi Yao, Zhemin Xia, Xia Xu, Xiaolan Su, Meijuan Huang, Lei Dai, Yang Yang, Shuang Zhang, Dechao Yu, Robert Chunhua Zhao, Yuquan Wei, Hongxin Deng
Autologous adipose tissue or adipose tissue with additive adipose-derived mesenchymal stem cells (ADSCs) is used in the breast reconstruction of breast cancer patients who undergo mastectomy. ADSCs play an important role in the angiogenesis and adipogenesis, which make it much better than other materials. However, ADSCs may promote residual tumor cells to proliferate or metastasize, and the mechanism is still not fully understood. In our present study, we demonstrated that hADSCs could facilitate tumor cells growth after co-injection with MCF7 and ZR-75-30 breast cancer cells (BCCs) by promoting angiogenesis, but hADSCs showed limited effect on the growth of MDA-MB-231 BCCs...
May 17, 2017: Stem Cells
https://www.readbyqxmd.com/read/28480607/adiponectin-enhances-quiescence-exit-of-murine-hematopoietic-stem-cells-and-hematopoietic-recovery-through-mtorc1-potentiation
#5
Yosuke Masamoto, Shunya Arai, Tomohiko Sato, Naoto Kubota, Iseki Takamoto, Takashi Kadowaki, Mineo Kurokawa
Myelotoxic injury, such as chemotherapeutic agents and ionizing radiation, unlocks the vigorous power of hematopoietic stem cells (HSCs) to replenish the hematopoietic system, making quiescent HSCs enter the cell cycle. Considering that both HSC-intrinsic and -extrinsic mechanisms enforce quiescence of HSCs, the drastic change in bone marrow (BM) environment after injury, represented by massive expansion of BM adipocytes, might trigger HSC activation. BM adipocytes, the major cellular component in the ablated marrow, however, reportedly suppress proliferation of hematopoietic cells, which may indicate the BM adipocytogenesis is an irrational response of injured organism...
May 8, 2017: Stem Cells
https://www.readbyqxmd.com/read/28480563/cell-therapy-in-parkinson-s-disease-host-brain-repair-machinery-gets-a-boost-from-stem-cell-grafts
#6
Eleonora Napoli, Cesar V Borlongan
This commentary highlights the major findings and future research directions arising from the recent publication by Zuo and colleagues in Stem Cells (2017). Here, we discuss the novel observations that transplanted human neural stem cells can induce endogenous brain repair by specifically stimulating a host of regenerative processes in the neurogenic niche (i.e., subventricular zone or SVZ) in an animal model of Parkinson's disease. That the identified therapeutic proteomes, neurotrophic factors, and anti-inflammatory cytokines in the SVZ may facilitate brain regeneration and behavioral recovery open a new venue of research for our understanding of the pathology and treatment of Parkinson's disease...
May 8, 2017: Stem Cells
https://www.readbyqxmd.com/read/28480592/slow-myofiber-commitment-by-semaphorin-3a-secreted-from-myogenic-stem-cells
#7
Ryuichi Tatsumi, Takahiro Suzuki, Mai-Khoi Q Do, Yuki Ohya, Judy E Anderson, Ayumi Shibata, Mai Kawaguchi, Shunpei Ohya, Hideaki Ohtsubo, Wataru Mizunoya, Shoko Sawano, Yusuke Komiya, Riho Ichitsubo, Koichi Ojima, Shin-Ichiro Nishimatsu, Tsutomu Nohno, Yutaka Ohsawa, Yoshihide Sunada, Mako Nakamura, Mitsuhiro Furuse, Yoshihide Ikeuchi, Takanori Nishimura, Takeshi Yagi, Ronald E Allen
Recently, we found that resident myogenic stem satellite cells up-regulate a multi-functional secreted protein, semaphorin 3A (Sema3A), exclusively at the early- differentiation phase in response to muscle injury; however, its physiological significance is still unknown. Here we show that Sema3A impacts slow-twitch fiber generation through a signaling pathway, cell-membrane receptor (neuropilin2-plexinA3) → myogenin-myocyte enhancer factor 2D (MEF2D) → slow myosin heavy chain. This novel axis was found by small interfering RNA (siRNA)-transfection experiments in myoblast cultures, which also revealed an additional element that Sema3A-neuropilin1/plexinA1, A2 may enhance slow-fiber formation by activating signals that inhibit fast-myosin expression...
May 7, 2017: Stem Cells
https://www.readbyqxmd.com/read/28480559/the-endothelial-protein-c-receptor-is-a-potential-stem-cell-marker-for-epidermal-keratinocytes
#8
Meilang Xue, Suat Dervish, Benjamin Chan, Christopher J Jackson
Endothelial protein C receptor (EPCR) is a specific receptor for anticoagulant protein C and expressed by human epidermis and cultured keratinocytes. Here we investigated whether: (a) the level of EPCR in keratinocytes is associated with their growth potential; and (b) EPCR is a potential marker for human epidermal stem cells. Human keratinocytes isolated from foreskins or adult skin tissues were transfected with EPCR siRNA or EPCR overexpressing plasmids. Cell proliferation, long term proliferation potential, colony forming efficiency (CFE), and in vitro epidermal regeneration ability of EPCR(high) and EPCR(l) °(w) cells were assessed...
May 7, 2017: Stem Cells
https://www.readbyqxmd.com/read/28472853/genetic-rescue-of-mitochondrial-and-skeletal-muscle-impairment-in-an-induced-pluripotent-stem-cells-model-of-coenzyme-q10-deficiency
#9
Damià Romero-Moya, Carlos Santos-Ocaña, Julio Castaño, Gloria Garrabou, José A Rodríguez-Gómez, Vanesa Ruiz-Bonilla, Clara Bueno, Patricia González-Rodríguez, Alessandra Giorgetti, Eusebio Perdiguero, Cristina Prieto, Constanza Moren-Nuñez, Daniel J Fernández-Ayala, Maria Victoria Cascajo, Iván Velasco, Josep Maria Canals, Raquel Montero, Delia Yubero, Cristina Jou, José López-Barneo, Francesc Cardellach, Pura Muñoz-Cánoves, Rafael Artuch, Plácido Navas, Pablo Menendez
Coenzyme Q10 (CoQ10 ) plays a crucial role in mitochondria as an electron carrier within the mitochondrial respiratory chain (MRC) and is an essential antioxidant. Mutations in genes responsible for CoQ10 biosynthesis (COQ genes) cause primary CoQ10 deficiency, a rare and heterogeneous mitochondrial disorder with no clear genotype-phenotype association, mainly affecting tissues with high-energy demand including brain and skeletal muscle (SkM). Here, we report a four-year-old girl diagnosed with minor mental retardation and lethal rhabdomyolysis harboring a heterozygous mutation (c...
May 4, 2017: Stem Cells
https://www.readbyqxmd.com/read/28470788/cd36-is-a-marker-of-human-adipocyte-progenitors-with-pronounced-adipogenic-and-triglyceride-accumulation-potential
#10
Hui Gao, Fanny Volat, Lakshmi Sandhow, Jean Galitzky, Thuy Nguyen, David Esteve, Gaby Åström, Niklas Mejhert, Severine Ledoux, Claire Thalamas, Peter Arner, Jean-Claude Guillemot, Hong Qian, Mikael Rydén, Anne Bouloumié
White adipose tissue (WAT) expands in part through adipogenesis, a process involving fat cell generation and fatty acid (FA) storage into triglycerides (TGs). Several findings suggest that inter-individual and regional variations in adipogenesis are linked to metabolic complications. We aimed to identify cellular markers that define human adipocyte progenitors (APs) with pronounced adipogenic/TG storage ability. Using an unbiased single cell screen of passaged human adipose-derived stromal cells (hADSCs) we identified cell clones with similar proliferation rates but discordant capabilities to undergo adipogenic differentiation...
May 4, 2017: Stem Cells
https://www.readbyqxmd.com/read/28436588/reduced-erg-dosage-impairs-survival-of-hematopoietic-stem-and-progenitor-cells
#11
Ying Xie, Mia Lee Koch, Xin Zhang, Melanie J Hamblen, Frank J Godinho, Yuko Fujiwara, Huafeng Xie, Jan-Henning Klusmann, Stuart H Orkin, Zhe Li
ERG, an ETS family transcription factor frequently overexpressed in human leukemia, has been implicated as a key regulator of hematopoietic stem cells. However, how ERG controls normal hematopoiesis, particularly at the stem and progenitor cell level, and how it contributes to leukemogenesis remain incompletely understood. Using homologous recombination, we generated an Erg knockdown allele (Erg(kd) ) in which Erg expression can be conditionally restored by Cre recombinase. Erg(kd/kd) animals die at E10.5-E11...
April 24, 2017: Stem Cells
https://www.readbyqxmd.com/read/28436570/bre-enhances-osteoblastic-differentiation-by-promoting-the-mdm2-mediated-degradation-of-p53
#12
Fujun Jin, Yiliang Wang, Xiaojing Wang, Yanting Wu, Xiaoyan Wang, Qiuying Liu, Yexuan Zhu, Enqi Liu, Jianglin Fan, Yifei Wang
Bre is a conserved cellular protein expressed in various tissues. Its major function includes DNA damage repair and anti-apoptosis. Recent studies indicate that Bre is potentially involved in stem cell differentiation although pathophysiological significance along with the molecular mechanisms is still unclear. Here, we report that Bre protein was substantially expressed in the bone tissue and its expression was highly upregulated during the osteogenic differentiation. To test a hypothesis that Bre plays functional roles in the process of osteogenic differentiation, we examined the expression of Bre in an osteoporosis mouse model...
April 24, 2017: Stem Cells
https://www.readbyqxmd.com/read/28436144/unacylated-ghrelin-enhances-satellite-cell-function-and-relieves-the-dystrophic-phenotype-in-duchenne-muscular-dystrophy-mdx-model
#13
Simone Reano, Elia Angelino, Michele Ferrara, Valeria Malacarne, Hana Sustova, Omar Sabry, Emanuela Agosti, Sara Clerici, Giulia Ruozi, Lorena Zentilin, Flavia Prodam, Stefano Geuna, Mauro Giacca, Andrea Graziani, Nicoletta Filigheddu
Muscle regeneration depends on satellite cells, quiescent precursors that, in consequence of injury or in pathological states such as muscular dystrophies, activate, proliferate, and differentiate to repair the damaged tissue. A subset of satellite cells undergoes self-renewal, thus preserving the satellite cell pool and its regenerative potential. Unacylated ghrelin (UnAG) is a circulating hormone that protects muscle from atrophy, promotes myoblast differentiation, and enhances ischemia-induced muscle regeneration...
April 24, 2017: Stem Cells
https://www.readbyqxmd.com/read/28436127/tip110-deletion-impaired-embryonic-and-stem-cell-development-involving-down-regulation-of-stem-cell-factors-nanog-oct4-and-sox2
#14
Amanda Whitmill, Ying Liu, Khalid Amine Timani, Yinghua Niu, Johnny J He
HIV-1 Tat-interacting protein of 110 kDa, Tip110, plays important roles in multiple biological processes. In this study, we aimed to characterize the function of Tip110 in embryonic development. Transgenic mice lacking expression of a functional Tip110 gene (Tip110(-/-) ) died post-implantation, and Tip110(-/-) embryos exhibited developmental arrest between 8.5 and 9.5 days post coitum. However, in vitro cultures of Tip110(-/-) embryos showed that Tip110 loss did not impair embryo growth from the zygote to the blastocyst...
April 24, 2017: Stem Cells
https://www.readbyqxmd.com/read/28406573/brief-report-robo1-regulates-the-migration-of-human-subventricular-zone-neural-progenitor-cells-during-development
#15
Hugo Guerrero-Cazares, Emily Lavell, Linda Chen, Paula Schiapparelli, Montserrat Lara-Velazquez, Vivian Capilla-Gonzalez, Anna Christina Clements, Gabrielle Drummond, Liron Noiman, Katrina Thaler, Anne Burke, Alfredo Quiñones-Hinojosa
Human neural progenitor cell (NPC) migration within the subventricular zone (SVZ) of the lateral ganglionic eminence is an active process throughout early brain development. The migration of human NPCs from the SVZ to the olfactory bulb during fetal stages resembles what occurs in adult rodents. As the human brain develops during infancy, this migratory stream is drastically reduced in cell number and becomes barely evident in adults. The mechanisms regulating human NPC migration are unknown. The Slit-Robo signaling pathway has been defined as a chemorepulsive cue involved in axon guidance and neuroblast migration in rodents...
April 13, 2017: Stem Cells
https://www.readbyqxmd.com/read/28398002/alpha-ketoglutarate-curbs-differentiation-and-induces-cell-death-in-mesenchymal-stromal-precursors-with-mitochondrial-dysfunction
#16
Karmveer Singh, Linda Krug, Abhijit Basu, Patrick Meyer, Nicolai Treiber, Seppe Vander Beken, Meinhard Wlaschek, Stefan Kochanek, Wilhelm Bloch, Hartmut Geiger, Pallab Maity, Karin Scharffetter-Kochanek
Increased concentrations of reactive oxygen species (ROS) originating from dysfunctional mitochondria contribute to diverse aging-related degenerative disorders. But so far little is known about the impact of distinct ROS on metabolism and fate of stromal precursor cells. Here, we demonstrate that an increase in superoxide anion radicals due to superoxide dismutase 2 (Sod2) deficiency in stromal precursor cells suppress osteogenic and adipogenic differentiation through fundamental changes in the global metabolite landscape...
April 11, 2017: Stem Cells
https://www.readbyqxmd.com/read/28390147/concise-review-stem-cells-in-osteoimmunology
#17
Fernando A Fierro, Jan A Nolta, Iannis E Adamopoulos
Bone remodeling is a lifelong process in which mature bone tissue is removed from the skeleton by bone resorption and is replenished by new during ossification or bone formation. The remodeling cycle requires both the differentiation and activation of two cell types with opposing functions; the osteoclast, which orchestrates bone resorption, and the osteoblast, which orchestrates bone formation. The differentiation of these cells from their respective precursors is a process which has been overshadowed by enigma, particularly because the precise osteoclast precursor has not been identified and because the identification of skeletal stem cells, which give rise to osteoblasts, is very recent...
April 8, 2017: Stem Cells
https://www.readbyqxmd.com/read/28376568/mesenchymal-stem-cell-microvesicles-attenuate-acute-lung-injury-in-mice-partly-mediated-by-ang-1-mrna
#18
Xiao-Dan Tang, Lin Shi, Antoine Monsel, Xiang-Yang Li, Hui-Li Zhu, Ying-Gang Zhu, Jie-Ming Qu
Microvesicles (MVs) derived from human mesenchymal stem cells (MSC MVs) were demonstrated to ameliorate inflammation in lungs. We have found their content of mRNA for keratinocyte growth factor was partly involved in their therapeutic effects. As MSC MVs also contained a substantial quantity of angiopoietin-1 (Ang-1) mRNA, which plays an essential role in vascular stabilization and resolving inflammation, we hypothesized that Ang-1 mRNA might similarly account for a part of their therapeutic effects. We downregulated Ang-1 mRNA expression in MVs, using a lentivirus vector carrying Ang-1 short hairpin RNA to transfect MSCs...
April 4, 2017: Stem Cells
https://www.readbyqxmd.com/read/28376567/hypoxia-inducible-factor-1%C3%AE-potentiates-jagged-1-mediated-angiogenesis-by-mesenchymal-stem-cell-derived-exosomes
#19
Hernán Gonzalez-King, Nahuel A García, Imelda Ontoria-Oviedo, María Ciria, José Anastasio Montero, Pilar Sepúlveda
Insufficient vessel growth associated with ischemia remains an unresolved issue in vascular medicine. Mesenchymal stem cells (MSCs) have been shown to promote angiogenesis via a mechanism that is potentiated by hypoxia. Overexpression of hypoxia inducible factor (HIF)-1α in MSCs improves their therapeutic potential by inducing angiogenesis in transplanted tissues. Here, we studied the contribution of exosomes released by HIF-1α-overexpressing donor MSCs (HIF-MSC) to angiogenesis by endothelial cells. Exosome secretion was enhanced in HIF-MSC...
April 4, 2017: Stem Cells
https://www.readbyqxmd.com/read/28376564/adipogenic-differentiation-of-mesenchymal-stem-cells-alters-their-immunomodulatory-properties-in-a-tissue-specific-manner
#20
Hafsa Munir, Lewis S C Ward, Lozan Sheriff, Samuel Kemble, Saba Nayar, Francesca Barone, Gerard B Nash, Helen M McGettrick
Chronic inflammation is associated with formation of ectopic fat deposits that might represent damage-induced aberrant mesenchymal stem cell (MSC) differentiation. Such deposits are associated with increased levels of inflammatory infiltrate and poor prognosis. Here we tested the hypothesis that differentiation from MSC to adipocytes in inflamed tissue might contribute to chronicity through loss of immunomodulatory function. We assessed the effects of adipogenic differentiation of MSC isolated from bone marrow or adipose tissue on their capacity to regulate neutrophil recruitment by endothelial cells and compared the differentiated cells to primary adipocytes from adipose tissue...
April 4, 2017: Stem Cells
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