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stem cell disease modelling

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https://www.readbyqxmd.com/read/29040534/macrophages-escape-klotho-gene-silencing-in-the-mdx-mouse-model-of-duchenne-muscular-dystrophy-and-promote-muscle-growth-and-increase-satellite-cell-numbers-through-a-klotho-mediated-pathway
#1
Michelle Wehling-Henricks, Steven S Welc, Guiseppina Samengo, Chiara Rinaldi, Catherine Lindsey, Ying Wang, Jeongyoon Lee, Makoto Kuro-O, James G Tidball
Duchenne muscular dystrophy (DMD) is a muscle wasting disease in which inflammation influences the severity of pathology. We found that the onset of muscle inflammation in the mdx mouse model of DMD coincides with large increases in expression of pro-inflammatory cytokines [tumor necrosis factor-α (TNFα); interferon gamma (IFNγ)] and dramatic reductions of the pro-myogenic protein Klotho in muscle cells and large increases of Klotho in pro-regenerative, CD206+ macrophages. Furthermore, TNFα and IFNγ treatments reduced Klotho in muscle cells and increased Klotho in macrophages...
October 12, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29040281/impaired-anti-fibrotic-effect-of-bone-marrow-derived-mesenchymal-stem-cell-in-a-mouse-model-of-pulmonary-paracoccidioidomycosis
#2
Julián Camilo Arango, Juan David Puerta-Arias, Paula Andrea Pino-Tamayo, Lina María Salazar-Peláez, Mauricio Rojas, Ángel González
Bone marrow-derived mesenchymal stem cells (BMMSCs) have been consider as a promising therapy in fibrotic diseases. Experimental models suggest that BMMSCs may be used as an alternative therapy to treat chemical- or physical-induced pulmonary fibrosis. We investigated the anti-fibrotic potential of BMMSCs in an experimental model of lung fibrosis by infection with Paracoccidioides brasiliensis. BMMSCs were isolated and purified from BALB/c mice using standardized methods. BALB/c male mice were inoculated by intranasal infection of 1...
October 17, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29040257/current-challenges-in-the-management-of-essential-thrombocythemia
#3
Ariel Kleman, Arun K Singavi, Laura C Michaelis
Essential thrombocythemia (ET), an uncommon blood cancer, is one of the classic myeloproliferative neoplasms, a category that also includes polycythemia vera and primary myelofibrosis. All 3 diseases are clonal hematopoietic stem cell disorders. Since 2005, when scientists discovered a molecular aberration driving clonal hematopoiesis in polycythemia vera, our understanding of the genomic underpinnings of these conditions has increased rapidly. Over the last decades, primary prevention of thrombotic and hemorrhagic complications has improved the lives of patients with ET, and the ability to characterize the disease by the presence or absence of molecular mutations has lent precision to our prognostic models...
October 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29036922/microrna-and-mrna-dysregulation-in-astrocytes-infected-with-zika-virus
#4
Robert A Kozak, Anna Majer, Mia J Biondi, Sarah J Medina, Lee W Goneau, Babu V Sajesh, Jessy A Slota, Vanessa Zubach, Alberto Severini, David Safronetz, Shannon L Hiebert, Daniel R Beniac, Timothy F Booth, Stephanie A Booth, Gary P Kobinger
The Zika virus (ZIKV) epidemic is an ongoing public health concern. ZIKV is a flavivirus reported to be associated with microcephaly, and recent work in animal models demonstrates the ability of the virus to cross the placenta and affect fetal brain development. Recent findings suggest that the virus preferentially infects neural stem cells and thereby deregulates gene expression, cell cycle progression, and increases cell death. However, neuronal stem cells are not the only brain cells that are susceptible to ZIKV and infection of other brain cells may contribute to disease progression...
October 14, 2017: Viruses
https://www.readbyqxmd.com/read/29035380/mixed-cell-therapy-of-bone-marrow-derived-mesenchymal-stem-cells-and-articular-cartilage-chondrocytes-ameliorates-osteoarthritis-development
#5
Indira Prasadam, Akoy Akuien, Thor E Friis, Wei Fang, Xinzhan Mao, Ross W Crawford, Yin Xiao
Of the many cell-based treatments that have been tested in an effort to regenerate osteoarthritic articular cartilage, none have ever produced cartilage that compare with native hyaline cartilage. Studies show that different cell types lead to inconsistent results and for cartilage regeneration to be considered successful, there must be an absence of fibrotic tissue. Here we report of a series of experiments in which bone marrow-derived stem cells (BMSCs) and articular cartilage chondrocytes (ACCs) were mixed in a 1:1 ratio and tested for their ability to enhance cartilage regeneration in three different conditions: (1) in an in vitro differentiation model; (2) in an ex vivo cartilage defect model implanted subcutaneously in mice; and (3) as an intra-articular injection in a meniscectomy-induced OA model in rats...
October 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29035359/acute-myeloid-leukaemia-disrupts-endogenous-myelo-erythropoiesis-by-compromising-the-adipocyte-bone-marrow-niche
#6
Allison L Boyd, Jennifer C Reid, Kyle R Salci, Lili Aslostovar, Yannick D Benoit, Zoya Shapovalova, Mio Nakanishi, Deanna P Porras, Mohammed Almakadi, Clinton J V Campbell, Michael F Jackson, Catherine A Ross, Ronan Foley, Brian Leber, David S Allan, Mitchell Sabloff, Anargyros Xenocostas, Tony J Collins, Mickie Bhatia
Acute myeloid leukaemia (AML) is distinguished by the generation of dysfunctional leukaemic blasts, and patients characteristically suffer from fatal infections and anaemia due to insufficient normal myelo-erythropoiesis. Direct physical crowding of bone marrow (BM) by accumulating leukaemic cells does not fully account for this haematopoietic failure. Here, analyses from AML patients were applied to both in vitro co-culture platforms and in vivo xenograft modelling, revealing that human AML disease specifically disrupts the adipocytic niche in BM...
October 16, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29034896/generation-of-induced-pluripotent-stem-cells-aro-ipsc1-11-from-a-patient-with-autosomal-recessive-osteopetrosis-harboring-the-c-212-1g-t-mutation-in-snx10-gene
#7
Maojia Xu, Eva-Lena Stattin, Mary Murphy, Frank Barry
Pathogenic sequence variants in the Sorting Nexin 10 (SNX10) gene have been associated with autosomal recessive osteopetrosis (ARO) in human. In this study, an induced pluripotent stem cell (iPSC) line (ARO-iPSC1-11) was generated from an ARO patient carrying the homozygous c.212+1G>T mutation in SNX10, using a retroviral-based reprogramming protocol. Characterization confirmed that the generated iPSCs expressed pluripotency markers, displayed normal karyotype, showed pluripotent differentiation capacity and retained the targeted mutation...
October 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29034890/derivation-of-a-disease-specific-human-induced-pluripotent-stem-cell-line-from-a-biliary-atresia-patient
#8
Lipeng Tian, Lindsey Eldridge, Pooja Chaudhari, Linyi Zhang, Robert A Anders, Kathleen B Schwarz, Zhaohui Ye, Yoon-Young Jang
Biliary atresia (BA) is a common cause of pediatric end-stage liver disease. While its etiology is not yet clear, evidence has suggested that BA results from interactions between genetic susceptibility and environmental factors. Disease relevant human cellular models of BA will facilitate identification of both genetic and environmental factors that are important for disease prevention and treatment. Here we report the generation of a human induced pluripotent stem cell line from a BA patient using episomal vectors...
October 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29034878/generation-of-an-induced-pluripotent-stem-cell-line-cscrmi001-a-from-a-patient-with-a-new-type-of-limb-girdle-muscular-dystrophy-lgmd-due-to-a-missense-mutation-in-poglut1-rumi
#9
Jianbo Wu, Samuel D Hunt, Nadine Matthias, Emilia Servián-Morilla, Jonathan Lo, Hamed Jafar-Nejad, Carmen Paradas, Radbod Darabi
Recently, a new type of limb-girdle muscular dystrophy (LGMD type 2Z) has been identified due to a missense mutation in POGLUT1 (protein O-glucosyltransferase-Rumi), an enzyme capable of adding glucose to a distinct serine residue of epidermal growth factor-like repeats containing a C-X-S-X-(P/A)-C consensus sequence such as Notch receptors. Affected patients demonstrate reduced Notch signaling, decreased muscle stem cell pool and hypoglycosylation of α-dystroglycan, leading to LGMD phenotype. Here we report the generation and characterization of an iPSC line (CSCRMi001-A) from a LGMD-2Z patient with missense mutation in POGLUT1 which can be used for in vitro disease modeling...
October 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29034591/organ-on-a-chip-platforms-a-convergence-of-advanced-materials-cells-and-microscale-technologies
#10
REVIEW
Samad Ahadian, Robert Civitarese, Dawn Bannerman, Mohammad Hossein Mohammadi, Rick Lu, Erika Wang, Locke Davenport-Huyer, Ben Lai, Boyang Zhang, Yimu Zhao, Serena Mandla, Anastasia Korolj, Milica Radisic
Significant advances in biomaterials, stem cell biology, and microscale technologies have enabled the fabrication of biologically relevant tissues and organs. Such tissues and organs, referred to as organ-on-a-chip (OOC) platforms, have emerged as a powerful tool in tissue analysis and disease modeling for biological and pharmacological applications. A variety of biomaterials are used in tissue fabrication providing multiple biological, structural, and mechanical cues in the regulation of cell behavior and tissue morphogenesis...
October 16, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29034206/leukemia-initiating-cells-in-t-cell-acute-lymphoblastic-leukemia
#11
REVIEW
Shi Hao Tan, Fatima Carla Bertulfo, Takaomi Sanda
T-cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy characterized by the clonal proliferation of immature T-cell precursors. T-ALL has many similar pathophysiological features to acute myeloid leukemia, which has been extensively studied in the establishment of the cancer stem cell (CSC) theory, but the CSC concept in T-ALL is still debatable. Although leukemia-initiating cells (LICs), which can generate leukemia in a xenograft setting, have been found in both human T-ALL patients and animal models, the nature and origin of LICs are largely unknown...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29033839/schisandra-chinensis-stem-ameliorates-3-nitropropionic-acid-induced-striatal-toxicity-via-activation-of-the-nrf2-pathway-and-inhibition-of-the-mapks-and-nf-%C3%AE%C2%BAb-pathways
#12
Eun-Jeong Kim, Minhee Jang, Min Jung Lee, Jong Hee Choi, Sung Joong Lee, Sun Kwang Kim, Dae Sik Jang, Ik-Hyun Cho
The beneficial value of the stems of Schisandra chinensis (SSC) in neurological diseases is unclear. We examined whether SSC aqueous extract (SSCE) alleviates striatal toxicity in a 3-nitropropionic acid (3-NPA)-induced mouse model of Huntington's disease (HD). SSCE (75, 150, or 300 mg/kg/day, p.o.) was given daily before or after 3-NPA treatment. Pre- and onset-treatment with SSCE displayed a significant protective effect and pretreatment was more effective as assessed by neurological scores and survival rate...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29033833/cell-based-therapies-for-tissue-fibrosis
#13
REVIEW
Rebecca Lim, Sharon D Ricardo, William Sievert
The development of tissue fibrosis in the context of a wound-healing response to injury is common to many chronic diseases. Unregulated or persistent fibrogenesis may lead to structural and functional changes in organs that increase the risk of significant morbidity and mortality. We will explore the natural history, epidemiology, and pathogenesis of fibrotic disease affecting the lungs, kidneys, and liver as dysfunction of these organs is responsible for a substantial proportion of global mortality. For many patients with end-stage disease, organ transplantation is the only effective therapy to prolong life...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29032648/kaposi-s-sarcoma-associated-herpesvirus-infection-modulates-the-proliferation-of-glioma-stem-like-cells
#14
Hyungtaek Jeon, Yun Hee Kang, Seung-Min Yoo, Myung-Jin Park, Jong Bae Park, Seung-Hoon Lee, Myung-Shin Lee
Glioblastoma multiforme is the most lethal malignant brain tumor. Despite many intensive studies, the prognosis of glioblastoma multiforme is currently very poor, with a median overall survival duration of 14 months and 2-year survival rates of less than 10%. Although viral infections have been emphasized as potential cofactors, their influences on pathways that support glioblastoma progression are not known. Some previous studies indicated that human Kaposi's sarcoma-associated herpesvirus (KSHV) was detected in healthy brains, and its microRNA was also detected in glioblastoma patients' plasma...
October 14, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29031704/evaluation-of-cooperative-anti-leukemic-effects-of-nilotinib-and-vildagliptin-in-ph-chronic-myeloid-leukemia
#15
Michael Willmann, Irina Sadovnik, Gregor Eisenwort, Martin Entner, Tina Bernthaler, Gabriele Stefanzl, Emir Hadzijusufovic, Daniela Berger, Harald Herrmann, Gregor Hoermann, Peter Valent, Thomas Rülicke
Chronic myeloid leukemia (CML) is a stem cell neoplasm characterized by the BCR/ABL1 oncogene. Although the disease can be kept under control using BCR/ABL1 tyrosine kinase inhibitors (TKI) in most cases, some patients relapse or have resistant disease which points to the need to identify new therapeutic targets in this malignancy. Recent data suggest that leukemic stem cell (LSC) in CML display the SC-mobilizing cell surface enzyme dipeptidyl-peptidase IV (DPPIV=CD26) in an aberrant manner. In the present study, we analyzed the effects of the DPPIV blocker vildagliptin as single agent or in combination with the BCR/ABL1 TKI imatinib or nilotinib on growth and survival of CML LSC in vitro and on LSC engraftment in an in vivo xenotransplantation NSG mouse model...
October 12, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/29030821/retroviral-transduction-of-quiescent-murine-hematopoietic-stem-cells
#16
Chun Shik Park, H Daniel Lacorazza
Hematopoietic stem cells (HSCs) represent an important target cell population in bone marrow transplantation, cell and gene therapy applications, and the development of leukemia models for research. Because the hematopoietic progeny carries the genetic information of HSCs and replenishes the blood and immune system, corrective gene transfer into HSCs provides an ideal therapeutic approach for many monogenic hematological diseases and a useful tool for studies of HSC function and blood formation in normal and malignant hematopoiesis...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29029852/human-adipose-tissue-derived-stem-cells-inhibit-the-activity-of-keloid-fibroblasts-and-fibrosis-in-a-keloid-model-by-paracrine-signaling
#17
Jianlan Liu, Jie Ren, Lina Su, Shimeng Cheng, Jing Zhou, Xiaolu Ye, Yabin Dong, Silei Sun, Fazhi Qi, Zhifei Liu, Jonathon Pleat, Hongjun Zhai, Ningwen Zhu
BACKGROUND: Human adipose tissue-derived mesenchymal stem cells (ASCs) have potential utility as modulators of the regeneration of tissue that is inflamed or scarred secondary to injuries such as burns or trauma. However, the effect of ASCs on one particular type of scarring, keloidal disease, remains unknown. The absence of an optimal model for investigation has hindered the development of an effective therapy using ASCs for keloids. OBJECTIVE: To investigate the influence of ASCs on angiogenesis, extracellular matrix deposition, and inflammatory cell influx in keloids...
October 10, 2017: Burns: Journal of the International Society for Burn Injuries
https://www.readbyqxmd.com/read/29028220/pediatric-brain-repair-from-endogenous-neural-stem-cells-of-the-subventricular-zone
#18
REVIEW
Yusuke Niimi, Steven W Levison
There is great interest in the regenerative potential of the neural stem cells and progenitors that populate the germinal zones of the immature brain. Studies using animal models of pediatric brain injuries have provided a clearer understanding of the responses of these progenitors to injury. In this review we have compared and contrasted the responses of the endogenous neural stem cells and progenitors of the subventricular zone in animal models of neonatal cerebral hypoxia-ischemia, neonatal stroke, congenital cardiac disease and pediatric traumatic brain injury...
October 13, 2017: Pediatric Research
https://www.readbyqxmd.com/read/29027744/concise-review-induced-pluripotent-stem-cell-models-for-neuropsychiatric-diseases
#19
REVIEW
Abidemi Adegbola, Luke A Bury, Chen Fu, Meixiang Zhang, Anthony Wynshaw-Boris
The major neuropsychiatric conditions of schizophrenia, affective disorders, and infantile autism are characterized by chronic symptoms of episodic, stable, or progressive nature that result in significant morbidity. Symptomatic treatments are the mainstay but do not resolve the underlying disease processes, which are themselves poorly understood. The prototype psychotropic drugs are of variable efficacy, with therapeutic mechanisms of action that are still uncertain. Thus, neuropsychiatric disorders are ripe for new technologies and approaches with the potential to revolutionize mechanistic understanding and drive the development of novel targeted treatments...
October 13, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29025705/differentiation-evaluation-and-application-of-human-induced-pluripotent-stem-cell-derived-endothelial-cells
#20
REVIEW
Yang Lin, Chang-Hyun Gil, Mervin C Yoder
The emergence of induced pluripotent stem cell (iPSC) technology paves the way to generate large numbers of patient-specific endothelial cells (ECs) that can be potentially delivered for regenerative medicine in patients with cardiovascular disease. In the last decade, numerous protocols that differentiate EC from iPSC have been developed by many groups. In this review, we will discuss several common strategies that have been optimized for human iPSC-EC differentiation and subsequent studies that have evaluated the potential of human iPSC-EC as a cell therapy or as a tool in disease modeling...
October 12, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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