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Stem Cells and Development

Sarah K Crain, Sally R Robinson, Kristen E Thane, Airiel M Davis, Dawn M Meola, Bruce A Barton, Vicky K Yang, Andrew M Hoffman
Mesenchymal stem cells (MSC) are widely investigated as potential therapeutic agents due to their potent immunomodulatory capacity. Although specific mechanisms by which MSC act on immune cells are emerging, many questions remain including the potential of extracellular vesicles (EV) to mediate biological activities. Canine MSCs are of interest for both veterinary and comparative models of disease and have been shown to suppress CD4pos T cell (T helper cell) proliferation. The aim of this study was to determine whether EV isolated from canine Wharton's jelly-derived MSC (WJ-MSC EV) suppress CD4pos T cell proliferation using biochemical mechanisms previously ascribed to soluble mediators (TGF-β and adenosine)...
November 9, 2018: Stem Cells and Development
Elizabeth Cortez-Toledo, Melanie Rose, Emmanuel Agu, Heather Dahlenburg, Wei Yao, Jan A Nolta, Ping Zhou
Mesenchymal stem/stromal cells (MSCs) offer great promise in the treatment of ischemic injuries including stroke, heart infarction and limb ischemia. However, poor cell survival after transplantation remains a major obstacle to achieve effective MSC therapies. To improve cell survival and retention, we transplanted human bone marrow MSCs with or without a specific pro-survival factor (PSF) cocktail consisting of IGF1, Bcl-XL, a caspase inhibitor, a mitochondrial pathway inhibitor and matrigel into the limbs of immune deficient mice, after induction of hindlimb ischemia...
November 6, 2018: Stem Cells and Development
Young-Woo Jeon, Jung-Yeon Lim, Keon-Il Im, Nayoun Kim, Young-Sun Nam, Yun-Jin Song, Seok-Goo Cho
Interleukin (IL)-10-producing type 1 regulatory T (Tr1) cells, which are Foxp3<sup>-</sup> memory T lymphocytes, play important roles in peripheral immune tolerance. We investigated whether Tr1 cells exert immunoregulatory effects in a mouse model of acute graft-versus-host disease (GVHD). Mouse CD4<sup>+</sup> T cells were induced to differentiate in vitro into Tr1 cells using vitamin D3 and dexamethasone, and these donor-derived Tr1 cells were infused on the day of bone marrow transplantation...
November 1, 2018: Stem Cells and Development
Felipe Serrano, William George Bernard, Alessandra Granata, Dharini Iyer, Ben Steventon, Matthew Kim, Ludovic Vallier, Laure Gambardella, Sanjay Sinha
The neural crest (NC) is a transient, multipotent cell population present during embryonic development. The NC can give rise to multiple cell types and is involved in a number of different diseases. Therefore, the development of new strategies to model NC in vitro enables investigations into the mechanisms involved in NC development and disease. Here we report a simple and efficient protocol to differentiate human pluripotent stem cells (HPSC) into NC using a chemically defined media, with basic fibroblast growth factor (FGF2) and the transforming growth factor-β inhibitor SB-431542...
October 30, 2018: Stem Cells and Development
Jin A Lee, Jieun An, Tong Mook Kang, Debojyoti De, Kyeong Kyu Kim
The commitment of pluripotent stem cells to the cardiac lineage has enormous potential in regenerative medicine interventions for several cardiac diseases. Thus, it is necessary to understand and regulate this differentiation process for potential clinical application. In this study, we developed defined conditions with chemical inducers for effective cardiac lineage commitment and elucidated the mechanism for high-efficiency differentiation. First, we designed a robust reporter-based platform to screen chemical inducers of cardiac differentiation in the mouse P19 teratocarcinoma cell line...
October 25, 2018: Stem Cells and Development
Fiona Cousins, Dorien F O, Yih Rue Ong, David T Breault, James A Deane, Caroline E Gargett
The regenerative capacity of the endometrium has been attributed to resident stem/progenitor cells. A number of stem/progenitor markers have been reported for human endometrial stem/progenitor cells, however the lack of convenient markers in the mouse has made experimental investigation into endometrial regeneration difficult. We recently identified endometrial epithelial, endothelial and immune cells which express a reporter for the stem/progenitor marker, mouse telomerase reverse transcriptase (mTert). Here we investigate the expression pattern of a GFP reporter for mTert promoter activity (mTert-GFP) in endometrial regeneration following a menses-like event...
October 25, 2018: Stem Cells and Development
JianGuo Cui, Guangxing Chen, Anthony S Perry, Salahadin Abdi
Some types of cells, if not all, that undergo signal exchanges in culture need to contact other cells for various reasons, such as cell-to-cell contact for growth inhibition. However, signal exchanges by cell-to-cell contact before proliferation has never been reported. Using time-lapse recording, we discovered the emergence of several astonishing cell-to-cell contact modes in bone marrow-derived mesenchymal stem/stromal cells (MSCs) before the cells divided. When the cells contacted with another, a huge temporary synapse-like structure formed for molecules exchanges; a cell-tissue particle was taken in by a recipient cell; two cells membranes formed infusion-like structure for a short time; even a 20-micron long and 5-micron wide cell tail was grafted to another cell...
October 25, 2018: Stem Cells and Development
Arthur Caplan, Stephen F Badylak, Arnold I Caplan, Lindsay Davies, Staffan Stromblad, Daniel Weiss, Katarina Le Blanc
October 23, 2018: Stem Cells and Development
Amy Jane McCaughey-Chapman, Bronwen Connor
The study and treatment of neurological disorders have been hampered by a lack of access to live, healthy or disease-affected human neurons. The recent advances in the field of cell reprogramming offer exciting new possibilities for disease modelling, drug development, and cell-based therapies. Since the derivation of human embryonic stem cells (hESC) and their differentiation into neurons, cell reprogramming technologies have built on these protocols to generate mature human neurons of disease-associated phenotypes from somatic cells...
October 20, 2018: Stem Cells and Development
Xiabei Yan, Yulei Shu, Jun He, Jun Zhao, Li Jia, Jianwei Xie, Yansong Sun, Zengming Zhao, Shuangqing Peng
Sulfur mustard (SM) exposure, whose symptoms are similar to radiation exposure, can lead to acute injury. Because mesenchymal stromal cells (MSCs) have been used to experimentally and clinically treat acute radiation syndrome, in this study, MSCs were intravenously injected into rats after percutaneous SM exposure. Then, we examined sternum and spleen samples by histopathological and immunohistochemical methods to observe pathological changes. Furthermore, blood samples were taken to test the white blood cell count (W...
October 20, 2018: Stem Cells and Development
Yashar Mehrbani Azar, Robyn Green, Carola Ulrike Niesler, Mari van de Vyver
Mesenchymal stem cells (MSCs) are a promising therapeutic tool for the treatment of nonhealing diabetic wounds. The pathological nature of the niche microenvironment limits the use of autologous cell therapy in diabetic patients. Prolonged exposure of endogenous MSCs to a pathological microenvironment in vivo reduces their ability to respond to environmental cues. This study investigated the effectiveness of ex vivo antioxidant treatment [N-acetylcysteine (7.5 mM NAC) and Ascorbic acid 2-phosphate (0.6 mM AAP)] to restore the paracrine function of diabetic MSCs...
October 18, 2018: Stem Cells and Development
Quanwen Li, Erica Louden, Jordan Zhou, Sascha Drewlo, Jing Dai, Elizabeth Ella Puscheck, Kang Chen, Daniel A Rappolee
Mouse Embryonic Stem Cells (mESC) are unique in their self-renewal and pluripotency. Hypothetically, mESCs model gestational stress effects or stresses of in vitro fertilization/assisted reproductive technologies or drug/environmental exposures that endanger embryos. Testing mESCs stress responses should diminish and expedite in vivo embryo screening. Transgenic mESCs for green fluorescent protein (GFP) reporters of differ-entiation use the promoter for platelet-derived growth factor receptor (Pdgfr)a driving GFP expression to moni-tor hyperosmotic stress-forced mESC proliferation decrease (stunting), and differentiation increase that further stunts mESC population growth...
October 17, 2018: Stem Cells and Development
Fan Ye, Florence Herr, Amelia Vernochet, Benoit Menneson, Estelle Oberlin, Antoine Durrbach
Mesenchymal stem cells (MSCs) are powerful immunomodulators that regulate the diverse functions of immune cells involved in allogeneic reactions, such as T cells and natural killer cells (NK), through cell-cell contact or secreted factors. Exosomes secreted by MSCs may be involved in their regulatory functions, providing new therapeutic tools. Here, we showed that fetal liver (FL) MSC-derived exosomes inhibit proliferation, activation, and cytotoxicity of NK cells. Exosomes bearing LAP, TGFβ, and TSP1, a regulatory molecule for TGFβ, induced downstream TGFβ/Smad2/3 signaling in NK cells...
October 17, 2018: Stem Cells and Development
Amanda L Patterson, Jitu George, Anindita Chatterjee, Tyler Carpenter, Emily Wolfrum, James K Pru, Jose M Teixeira
Uterine remodeling during pregnancy and postpartum uterine involution are two fundamental, dynamic processes that are required for successful propagation of eutherian species. The uterus can increase in size up to 40-fold during pregnancy, which is largely attributed to expansion of the myometrium by hyperplasia and hypertrophy. Following pregnancy, the uterus repairs the remodeled or "damaged" tissue during uterine involution. Little is known about this repair process, particularly the role of mesenchymal stem/progenitor cells...
October 17, 2018: Stem Cells and Development
Umesh Goyal, Malancha Ta
Mesenchymal Stem Cells (MSCs) are successful for their therapeutic application in immune and inflammatory contexts due to their anti-inflammatory, trophic and immunomodulatory roles. However, though MSCs have the potential to provide regenerative treatment towards a wide range of devastating diseases, massive cell death of transplanted MSCs remains an obstacle to overcome. The relation between MSCs and inflammation is multifactorial and challenging to comprehend. Fever is a critical component of the inflamed microenvironment...
October 15, 2018: Stem Cells and Development
Yang Zhao, Zhuo Yang, Yuan Wang, Yubing Luo, Fan Da, Wenjing Tao, Linyan Zhou, Deshou Wang, Jing Wei
Glial cell-derived neurotrophic factor family receptor alpha-1 (GFRα1) plays a crucial role in the self-renewal and maintenance of spermatogonial stem cells (SSCs) from mammals. However, to date, our knowledge about its role in fish SSCs is limited. In the present study, the medaka (Oryzias latipes) gfrα1 duplicate genes, Olgfrα1a and Olgfrα1b, were cloned and characterized. Furthermore, their expression profile and biological activity were investigated. OlGfrα1a and OlGfrα1b contain 524 and 466 amino acid residues, respectively...
October 15, 2018: Stem Cells and Development
Alejandro De Los Angeles, Insoo Hyun, Stephen Latham, John Elsworth, Eugene Redmond
The search for a better animal model to simulate human disease has been a "holy grail" of biomedical research for decades. Recent identification of different types of pluripotent stem cells (PS cells) and advances in chimera research might soon permit the generation of interspecies chimeras from closely related species, such as those between humans and other primates. Here, we suggest that the creation of human-primate chimeras - specifically, the transfer of human stem cells into (non-ape) primate hosts - could surpass the limitations of current monkey models of neurological and psychiatric disease, but would also raise important ethical considerations concerning the use of monkeys in invasive research...
October 15, 2018: Stem Cells and Development
Zuolian Shen, Tim Formosa, Dean Tantin
The histone chaperone FACT is associated with nuclear processes including DNA transcription, replication and repair. We previously showed that FACT is transiently recruited to pluripotency-associated target genes by newly-bound Oct4. Here we tested the effects of FACT depletion by knockout or chemical inhibition on the induction and maintenance of pluripotency. CRISPR-mediated deletion of the FACT subunit Spt16 did not affect the viability or proliferation of fibroblasts, but blocked their ability to form induced pluripotent stem cells...
October 15, 2018: Stem Cells and Development
Lucas-Sebastian Spitzhorn, Claus Kordes, Matthias Megges, Iris Sawitza, Silke Götze, Doreen Reichert, Peggy Schulze-Matz, Nina Graffmann, Martina Bohndorf, Wasco Wruck, Jan Philipp Köhler, Diran Herebian, Ertan Mayatepek, Richard O Oreffo, Dieter Häussinger, James Adjaye
Gunn rats bear a mutation within the uridine diphosphate glucuronosyltransferase-1A1 (Ugt1a1) gene resulting in high serum bilirubin levels as seen in Crigler-Najjar syndrome. In the present study, the Gunn rat was used as an animal model for heritable liver dysfunction. Human mesenchymal stem cells (iMSC) derived from embryonic stem cells (H1) and induced pluripotent stem cells were transplanted into Gunn rats after partial hepatectomy. The iMSCs engrafted and survived in the liver for up to 2 months. The transplanted iMSCs differentiated into functional hepatocytes as evidenced by partially suppressed hyperbilirubinemia and expression of multiple human-specific hepatocyte markers such as Albumin, hepatocyte nuclear factor 4α, UGT1A1, Cytokeratin 18, bile salt export pump, multidrug resistance protein 2, Na/taurocholate-cotransporting polypeptide and α-Fetoprotein...
October 3, 2018: Stem Cells and Development
Amir H Alizadeh, Ritesh Briah, Daniel A F Villagómez, Allan King, Thomas G Koch
The aim of the present work was to determine proliferation capacity, immunophenotype and genome integrity of mesenchymal stromal cells (MSCs) from horse umbilical cord blood (UCB) at passage stage 5 and 10. Passage four cryopreserved UCB-MSCs from six unrelated donors were evaluated. Immunophenotypic analysis of UCB-MSC revealed a cell identity consistent with equine MSC phenotype by high expression of CD90, CD44, CD29 and very low expression of CD4, CD11a/18, CD73, and MHC class I and II antigens. Proliferative differences were noted among the UCB-MSC cultures...
September 25, 2018: Stem Cells and Development
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