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Stem Cells

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https://www.readbyqxmd.com/read/28102558/concise-reviews-regeneration-in-mammalian-cochlea-hair-cells-help-from-supporting-cells-transdifferentiation
#1
Bénédicte Franco, Brigitte Malgrange
It is commonly assumed that mammalian cochlear cells do not regenerate. Therefore, if hair cells are lost following an injury, no recovery could occur. However, during the first postnatal week, mice harbor some progenitor cells that retain the ability to give rise to new hair cells. These progenitor cells are in fact supporting cells. Upon hair cells loss, those cells are able to generate new hair cells both by direct transdifferentiation or following cell cycle re-entry and differentiation. However, this property of supporting cells is progressively lost after birth...
January 19, 2017: Stem Cells
https://www.readbyqxmd.com/read/28100040/induced-pluripotent-stem-cell-research-in-the-era-of-precision-medicine
#2
Takashi Hamazaki, Nihal El Rouby, Natalie C Fredette, Katherine E Santostefano, Naohiro Terada
Recent advances in DNA sequencing technologies are revealing how human genetic variations associate with differential health risks, disease susceptibilities and drug responses. Such information is now expected to help evaluate individual health risks, design personalized health plans and treat patients with precision. It is still challenging, however, to understand how such genetic variations cause the phenotypic alterations in pathobiologies and treatment response. Human induced pluripotent stem cell (iPSC) technologies are emerging as a promising strategy to fill the knowledge gaps between genetic association studies and underlying molecular mechanisms...
January 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28100039/low-dose-radiation-causes-skin-cancer-in-mice-and-has-a-differential-effect-on-distinct-epidermal-stem-cells
#3
Tatiana Revenco, Gaelle Lapouge, Virginie Moers, Sylvain Brohée, Panagiota A Sotiropoulou
The carcinogenic effect of ionizing radiation has been evaluated based on limited populations accidently exposed to high dose radiation. In contrast, insufficient data are available on the effect of low dose radiation, such as radiation deriving from medical investigations and interventions, as well as occupational exposure that concern a large fraction of western populations. Using mouse skin epidermis as a model, we showed that low dose radiation results in DNA damage in sebaceous gland and bulge epidermal stem cells (SCs)...
January 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28100035/stromal-cells-act-as-guardians-for-endothelial-progenitors-by-reducing-their-immunogenicity-after-co-transplantation
#4
Naima Souidi, Meaghan Stolk, Juliane Rudeck, Dirk Strunk, Katharina Schallmoser, Hans-Dieter Volk, Martina Seifert
Regeneration of injured tissues requires effective therapeutic strategies supporting vasculogenesis. The lack of instantly available autologous cell sources and immunogenicity of allogeneic endothelial (progenitor) cells limits clinical progress. Based on the immunosuppressive potency of mesenchymal strem/progenitor cells (MSCs), we investigated whether crosstalk between endothelial colony-forming progenitor cells (ECFCs) and MSCs during vasculogenesis could lower allogeneic T cell responses against ECFCs allowing long-term engraftment in vivo...
January 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28100034/murine-rankl-mesenchymal-stromal-cells-display-an-osteogenic-differentiation-defect-improved-by-a-rankl-expressing-lentiviral-vector
#5
Francesca Schena, Ciro Menale, Emanuela Caci, Lorenzo Diomede, Eleonora Palagano, Camilla Recordati, Monica Sandri, Anna Tampieri, Ileana Bortolomai, Valentina Capo, Claudia Pastorino, Arinna Bertoni, Marco Gattorno, Alberto Martini, Anna Villa, Elisabetta Traggiai, Cristina Sobacchi
Autosomal Recessive Osteopetrosis (ARO) is a severe bone disease characterized by increased bone density due to impairment in osteoclast resorptive function or differentiation. Hematopoietic stem cell transplantation (HSCT) is the only available treatment; however, this therapy is not effective in RANKL-dependent ARO, since in bone this gene is mainly expressed by cells of mesenchymal origin. Of note, whether lack of RANKL production might cause a defect also in the bone marrow (BM) stromal compartment, possibly contributing to the pathology, is unknown...
January 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28100021/identifying-the-biphasic-role-of-calcineurin-nfat-signaling-enables-replacement-of-sox2-in-somatic-cell-reprogramming
#6
Sherif Khodeer, Takumi Era
Induction of pluripotency with defined factors (Oct4, Sox2, Klf4, c-Myc) raises hopes for successful clinical trials. Despite considerable efforts, the molecular mechanism of reprogramming remains poorly understood. The aim of the present study was to identify the role of calcineurin/nuclear factor of activated T cells (NFAT) in reprogramming. Our results demonstrated a biphasic role for calcineurin/NFAT signaling during reprogramming. In the early phase of reprogramming, calcineurin activity is required to maintain proper cell cycle division and for mesenchymal-epithelial transition...
January 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28090751/a-safety-checkpoint-to-eliminate-cancer-risk-of-the-immune-evasive-cells-derived-from-human-embryonic-stem-cells
#7
Jingjin He, Zhili Rong, Xuemei Fu, Yang Xu
Human embryonic stem cells (hESCs) hold great promise in the regenerative therapy of many currently untreatable human diseases. One of the key bottlenecks is the immune rejection of hESC-derived allografts by the recipient. To overcome this challenge, we have established new approaches to induce immune protection of hESC-derived allografts through the co-expression of immune suppressive molecules CTLA4-Ig and PD-L1. However, this in turn raises a safety concern of cancer risk because these hESC-derived cells can evade immune surveillance...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28090714/transplantation-of-cd51-stem-leydig-cells-a-new-strategy-for-the-treatment-of-testosterone-deficiency
#8
Zhi Jun Zang, Jiancheng Wang, Zhihong Chen, Yan Zhang, Yong Gao, Zhijian Su, Ying Tuo, Yan Liao, Min Zhang, Qunfang Yuan, Chunhua Deng, Mei Hua Jiang, Andy Peng Xiang
Stem Leydig cell (SLC) transplantation could provide a new strategy for treating the testosterone deficiency. Our previous study demonstrated that CD51 (also called integrin αv) might be a putative cell surface marker for SLCs, but the physiological function and efficacy of CD51(+) SLCs treatment remain unclear. Here, we explore the potential therapeutic benefits of CD51(+) SLCs transplantation and whether these transplanted cells can be regulated by the hypothalamic-pituitary-gonadal (HPG) axis. CD51(+) cells were isolated from the testes of 12-weeks-old C57BL/6 mice, and we showed that such cells expressed SLC markers and that they were capable of self-renewal, extensive proliferation, and differentiation into multiple mesenchymal cell lineages and LCs in vitro...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28090703/differentiation-of-islet-progenitors-regulated-by-nicotinamide-into-transcriptome-verified-%C3%AE-cells-that-ameliorate-diabetes
#9
Fang-Xu Jiang, Kevin Li, Michael Archer, Munish Mehta, Emma Jamieson, Adrian Charles, Jan E Dickinson, Masahito Matsumoto, Grant Morahan
Developmental stage-specific differentiation of stem or progenitor cells into safe and functional cells is of fundamental importance in regenerative medicine, including β-cell replacement. However, the differentiation of islet progenitor cells (IPCs) into insulin-secreting β cells remains elusive. Here, we report that the multi-functional molecule nicotinamide (NIC) is a specific differentiation regulator of mouse IPCs. The differentiated cells regulated by NIC exhibited many characteristics of adult β cells, including ameliorating preclinical diabetes and a highly comparable transcriptome profile...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28090699/modelling-irf8-deficient-human-hematopoiesis-and-dendritic-cell-development-with-engineered-ips-cells
#10
Stephanie Sontag, Malrun Förster, Jie Qin, Paul Wanek, Saskia Mitzka, Herdit M Schüler, Steffen Koschmieder, Stefan Rose-John, Kristin Seré, Martin Zenke
Human induced pluripotent stem (iPS) cells can differentiate into cells of all three germ layers, including hematopoietic stem cells and their progeny. Interferon regulatory factor 8 (IRF8) is a transcription factor, which acts in hematopoiesis as lineage determining factor for myeloid cells, including dendritic cells (DC). Autosomal recessive or dominant IRF8 mutations occurring in patients cause severe monocytic and DC immunodeficiency. To study IRF8 in human hematopoiesis we generated human IRF8-/- iPS cells and IRF8-/- embryonic stem (ES) cells using RNA guided CRISPR/Cas9n genome editing...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28090691/peg3-pw1-is-a-marker-of-a-subset-of-vessel-associated-endothelial-progenitors
#11
Matteo Malinverno, Monica Corada, Luca Ferrarini, Luigi Formicola, Giovanna Marazzi, David Sassoon, Elisabetta Dejana
Vascular associated endothelial cell progenitors are still poorly studied and their role in the newly forming vasculature at embryonic or postnatal stage remains elusive. In the present work we first defined a set of genes highly expressed during embryo development and strongly down regulated in the adult mouse. In this group we then concentrated on the progenitor cell marker Peg3/PW1. By in vivo staining of the vasculature we found that only a subset of cells co-expressed endothelial markers and PW1. These cells were quite abundant in the embryo vasculature but declined in number at postnatal and adult stages...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28090688/exosomal-mir-146a-contributes-to-the-enhanced-therapeutic-efficacy-of-il-1%C3%AE-primed-mesenchymal-stem-cells-against-sepsis
#12
Yuxian Song, Huan Dou, Xiujun Li, Xiaoyin Zhao, Yi Li, Dan Liu, Jianjian Ji, Fei Liu, Liang Ding, Yanhong Ni, Yayi Hou
Improving the immunomodulatory efficacy of mesenchymal stem cells (MSCs) through pretreatment with pro-inflammatory cytokines is an evolving field of investigation. However, the underlying mechanisms have not been fully clarified. Here, we pretreated human umbilical cord-derived MSCs with interleukin-1β (IL-1β) and evaluated their therapeutic effects in a cecal ligation and puncture (CLP)-induced sepsis model. We found that systemic administration of IL-1β-pretreated MSCs (βMSCs) ameliorated the symptoms of murine sepsis more effectively and increased the survival rate compared with naïve MSCs...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28032673/dental-pulp-stem-cells-model-early-life-and-imprinted-dna-methylation-patterns
#13
Keith Dunaway, Sarita Goorha, Lauren Matelski, Nora Urraca, Pamela J Lein, Ian Korf, Lawrence T Reiter, Janine M LaSalle
Early embryonic stages of pluripotency are modeled for epigenomic studies primarily with human embryonic stem cells (ESC) or induced pluripotent stem cells (iPSCs). For analysis of DNA methylation however, ESCs and iPSCs do not accurately reflect the DNA methylation levels found in preimplantation embryos. Whole genome bisulfite sequencing (WGBS) approaches have revealed the presence of large partially methylated domains (PMDs) covering 30%-40% of the genome in oocytes, preimplantation embryos, and placenta...
December 29, 2016: Stem Cells
https://www.readbyqxmd.com/read/28026131/sphingosine-1-phosphate-receptor-3-supports-hematopoietic-stem-and-progenitor-cell-residence-within-the-bone-marrow-niche
#14
Molly E Ogle, Claire E Olingy, Anthony O Awojoodu, Anusuya Das, Rafael A Ortiz, Hoi Yin Cheung, Edward A Botchwey
Hematopoietic stem and progenitor cells (HSPCs) egress from bone marrow (BM) during homeostasis and at increased rates during stress; however, the mechanisms regulating their trafficking remain incompletely understood. Here we describe a novel role for lipid receptor, sphingosine-1-phosphate receptor 3 (S1PR3), in HSPC residence within the BM niche. HSPCs expressed increased levels of S1PR3 compared to differentiated BM cells. Pharmacological antagonism or knockout (KO) of S1PR3 mobilized HSPCs into blood circulation, suggesting that S1PR3 influences niche localization...
December 27, 2016: Stem Cells
https://www.readbyqxmd.com/read/28026090/the-mesenchymal-precursor-cell-marker-antibody-stro-1-binds-to-cell-surface-heat-shock-cognate-70
#15
Stephen Fitter, Stan Gronthos, Soo Siang Ooi, Andrew C W Zannettino
Since its discovery more than 25 years ago, the STRO-1 antibody has played a fundamental role in defining the hierarchical nature of mesenchymal precursor cells (MPC) and their progeny. STRO-1 antibody binding remains a hallmark of immature pluripotent MPC. Despite the significance of STRO-1 in the MPC field, the identity of the antigen has remained elusive. Using a combination of 2-dimensional gel electrophoresis, coupled with Western blotting and Tandem mass spectroscopy, we have identified the STRO-1 antigen as heat shock cognate 70 (HSC70;HSPA8)...
December 27, 2016: Stem Cells
https://www.readbyqxmd.com/read/28026072/activation-of-klf1-enhances-the-differentiation-and-maturation-of-red-blood-cells-from-human-pluripotent-stem-cells
#16
Cheng-Tao Yang, Rui Ma, Richard A Axton, Melany Jackson, A Helen Taylor, Antonella Fidanza, Lamin Marenah, Jan Frayne, Joanne C Mountford, Lesley M Forrester
Blood transfusion is widely used in the clinic but the source of red blood cells (RBCs) is dependent on donors, procedures are susceptible to transfusion-transmitted infections and complications can arise from immunological incompatibility. Clinically-compatible and scalable protocols that allow the production of RBCs from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have been described but progress to translation has been hampered by poor maturation and fragility of the resultant cells...
December 27, 2016: Stem Cells
https://www.readbyqxmd.com/read/28009085/protein-tyrosine-phosphatase-prl2-mediates-notch-and-kit-signals-in-early-t-cell-progenitors
#17
Michihiro Kobayashi, Sarah Nabinger, Yunpeng Bai, Momoko Yoshimoto, Rui Gao, Sisi Chen, Chonghua Yao, Yuanshu Dong, Lujuan Zhang, Sonia Rodriguez, Yumi Yashiro-Ohtani, Warren S Pear, Nadia Carlesso, Mervin C Yoder, Reuben Kapur, Mark H Kaplan, H Daniel Lacorazza, Zhong-Yin Zhang, Yan Liu
The molecular pathways regulating lymphoid priming, fate, and development of multipotent bone marrow hematopoietic stem and progenitor cells (HSPCs) that continuously feed thymic progenitors remain largely unknown. While Notch signal is indispensable for T cell specification and differentiation, the downstream effectors are not well understood. PRL2, a protein tyrosine phosphatase that regulates hematopoietic stem cell proliferation and self-renewal, is highly expressed in murine thymocyte progenitors. Here we demonstrate that protein tyrosine phosphatase PRL2 and receptor tyrosine kinase c-Kit are critical downstream targets and effectors of the canonical Notch/RBPJ pathway in early T cell progenitors...
December 23, 2016: Stem Cells
https://www.readbyqxmd.com/read/28009074/new-monoclonal-antibodies-to-defined-cell-surface-proteins-on-human-pluripotent-stem-cells
#18
Carmel M O'Brien, Hun S Chy, Qi Zhou, Shiri Blumenfeld, Jack W Lambshead, Xiaodong Liu, Joshua Kie, Bianca D Capaldo, Tung-Liang Chung, Timothy E Adams, Tram Phan, John D Bentley, William J Mckinstry, Karen Oliva, Paul J Mcmurrick, Yu-Chieh Wang, Fernando J Rossello, Geoffrey J Lindeman, Di Chen, Thierry Jarde, Amander T Clark, Helen E Abud, Jane E Visvader, Christian M Nefzger, Jose M Polo, Jeanne F Loring, Andrew L Laslett
The study and application of human pluripotent stem cells (hPSCs) will be enhanced by the availability of well-characterised monoclonal antibodies (mAbs) detecting cell-surface epitopes. Here we report generation of seven new mAbs that detect cell surface proteins present on live and fixed human ES cells (hESCs) and human iPS cells (hiPSCs), confirming our previous prediction that these proteins were present on the cell surface of hPSCs. The mAbs all show a high correlation with POU5F1 (OCT4) expression and other hPSC surface markers (TRA-160 and SSEA-4) in hPSC cultures and detect rare OCT4 positive cells in differentiated cell cultures...
December 23, 2016: Stem Cells
https://www.readbyqxmd.com/read/28009066/amniotic-fluid-stem-cells-the-known-the-unknown-and-potential-regenerative-medicine-applications
#19
Stavros P Loukogeorgakis, Paolo De Coppi
The amniotic fluid has been identified as an untapped source of cells with broad potential, which possess immunomodulatory properties and don't have the ethical and legal limitations of embryonic stem cells. CD117(c-Kit)+ cells selected from amniotic fluid have been shown to differentiate into cell lineages representing all three embryonic germ layers without generating tumours, making them ideal candidates for regenerative medicine applications. Moreover, their ability to engraft in injured organs and modulate immune and repair responses of host tissues, suggest that transplantation of such cells may be useful for the treatment of various degenerative and inflammatory diseases...
December 23, 2016: Stem Cells
https://www.readbyqxmd.com/read/27977075/a-reinterpretation-of-cell-transplantation-gfp-transfer-from-donor-to-host-photoreceptors
#20
Arturo Ortin-Martinez, En Leh Samuel Tsai, Philip E Nickerson, Miriam Bergeret, Yao Lu, Sheila Smiley, Lacrimioara Comanita, Valerie A Wallace
The utilization of fluorescent reporter transgenes to discriminate donor versus host cells has been a mainstay of photoreceptor transplantation research, the assumption being that the presence of reporter+ cells in outer nuclear layer (ONL) of transplant recipients represents the integration of donor photoreceptors. We previously reported that GFP(+) cells in the ONL of cone-GFP transplanted retinas exhibited rod-like characteristics, raising the possibility that GFP signal in recipient tissue may not be a consequence of donor cell integration...
December 14, 2016: Stem Cells
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