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https://www.readbyqxmd.com/read/28646406/podocytes-and-the-quest-for-precision-medicines-for-kidney-diseases
#1
REVIEW
Peter Mundel
In this review, I describe a 30-year journey in the quest for precision medicines for patients with kidney diseases. In 1987, when I started my reseach career, most scientists studying glomerular disease biology were focused on mesangial cells. The crucial role of the podocyte in many kidney diseases characterized by proteinuria, including focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy, had not yet been recognized. We were not aware of genetic causes or drivers of kidney diseases nor of molecular markers and cell culture systems for mechanistic studies of podocyte biology...
June 23, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28645005/application-of-stem-cell-derived-neuronal-cells-to-evaluate-neurotoxic-chemotherapy
#2
Claudia Wing, Masaaki Komatsu, Shannon M Delaney, Matthew Krause, Heather E Wheeler, M Eileen Dolan
The generation of induced pluripotent stem cells (iPSCs) and differentiation to cells composing major organs has opened up the possibility for a new model system to study adverse toxicities associated with chemotherapy. Therefore, we used human iPSC-derived neurons to study peripheral neuropathy, one of the most common adverse effects of chemotherapy and cause for dose reduction. To determine the utility of these neurons in investigating the effects of neurotoxic chemotherapy, we measured morphological differences in neurite outgrowth, cell viability as determined by ATP levels and apoptosis through measures of caspase 3/7 activation following treatment with clinically relevant concentrations of platinating agents (cisplatin, oxaliplatin and carboplatin), taxanes (paclitaxel, docetaxel and nab-paclitaxel), a targeted proteasome inhibitor (bortezomib), an antiangiogenic compound (thalidomide), and 5-fluorouracil, a chemotherapeutic that does not cause neuropathy...
June 15, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28643534/transplantation-of-mouse-induced-pluripotent-stem-cells-into-the-cochlea-for-the-treatment-of-sensorineural-hearing-loss
#3
Jing Chen, Lina Guan, Hengtao Zhu, Shan Xiong, Liang Zeng, Hongqun Jiang
CONCLUSION: Mouse-induced pluripotent stem cells (iPSCs) could differentiate into hair cell-like cells and spiral ganglion-like cells after transplantation into mouse cochleae, but it cannot improve the auditory brain response (ABR) thresholds in short term. OBJECTIVE: To evaluate the potential of iPSCs for use as a source of transplants for the treatment of sensorineural hearing loss (SNHL). METHODS: Establishing SNHL mice model, then injecting the iPSCs or equal volume DMEM basic medium into the cochleae, respectively...
June 23, 2017: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/28643190/mitochondrial-biogenesis-and-neural-differentiation-of-human-ipsc-is-modulated-by-idebenone-in-a-developmental-stage-dependent-manner
#4
J Augustyniak, J Lenart, M Zychowicz, P P Stepien, L Buzanska
Idebenone, the synthetic analog of coenzyme Q10 can improve electron transport in mitochondria. Therefore, it is used in the treatment of Alzheimer's disease and other cognitive impairments. However, the mechanism of its action on neurodevelopment is still to be elucidated. Here we demonstrate that the cellular response of human induced pluripotent stem cells (hiPSC) to idebenone depends on the stage of neural differentiation. When: neural stem cells (NSC), early neural progenitors (eNP) and advanced neural progenitors (NP) have been studied a significant stimulation of mitochondrial biogenesis was observed only at the eNP stage of development...
June 22, 2017: Biogerontology
https://www.readbyqxmd.com/read/28637620/runx1-deficiency-familial-platelet-disorder-with-predisposition-to-myeloid-leukemia-fpdmm
#5
REVIEW
Brigitte Schlegelberger, Paula G Heller
In this review, we discuss disease-causing alterations of RUNT-related transcription factor 1 (RUNX1), a master regulator of hematopoietic differentiation. Familial platelet disorder with predisposition to myeloid leukemia (FPDMM) typically presents with (1) mild to moderate thrombocytopenia with normal-sized platelets; (2) functional platelets defects leading to prolonged bleeding; and (3) an increased risk to develop myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), or T-cell acute lymphoblastic leukemia (T-ALL)...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28637492/expression-patterns-of-fshd-causing-dux4-and-myogenic-transcription-factors-pax3-and-pax7-are-spatially-distinct-in-differentiating-human-stem-cell-cultures
#6
Premi Haynes, Kelly Kernan, Suk-Lin Zhou, Daniel G Miller
BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is most commonly inherited in an autosomal dominant pattern and caused by the abnormal expression of DUX4 in skeletal muscle. The DUX4 transcription factor has DNA binding domains similar to several paired class homeotic transcription factors, but only myogenic factors PAX3 and PAX7 rescue cell viability when co-expressed with DUX4 in mouse myoblasts. This observation suggests competition for DNA binding sites in satellite cells might limit muscle repair and may be one aspect of DUX4-associated myotoxicity...
June 21, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28637335/astrocyte-produced-mir-146a-as-a-mediator-of-motor-neuron-loss-in-spinal-muscular-atrophy
#7
Samantha L Sison, Teresa N Patitucci, Emily R Seminary, Eric Villalon, Christian L Lorson, Allison D Ebert
Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, is caused by loss of the survival motor neuron-1 (SMN1) gene, which leads to motor neuron loss, muscle atrophy, respiratory distress, and death. Motor neurons exhibit the most profound loss, but the mechanisms underlying disease pathogenesis are not fully understood. Recent evidence suggests that motor neuron extrinsic influences, such as those arising from astrocytes, contribute to motor neuron malfunction and loss. Here we investigated both loss-of-function and toxic gain-of-function astrocyte mechanisms that could play a role in SMA pathology...
June 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28636360/proneurogenic-effects-of-trazodone-in-murine-and-human-neural-progenitors
#8
Valeria Bortolotto, Francesca Mancini, Giorgina Mangano, Rita Salem, Er Xia, Erika Del Grosso, Michele Bianchi, Pier Luigi Canonico, Lorenzo Polenzani, Mariagrazia Grilli
Several antidepressants increase adult hippocampal Neurogenesis (ahNG) in rodents, primates and, potentially, in humans. This effect may at least partially account for their therapeutic activity. The availability of antidepressants whose mechanism of action involves different neurotransmitter receptors represents an opportunity for increasing our knowledge on their distinctive peculiarities and for dissecting the contribution of receptor subtypes in ahNG modulation. The aim of this study was to evaluate, in vitro, the effects of the antidepressant trazodone (TZD) on ahNG by using primary cultures of adult hippocampal Neural Progenitor Cells (ahNPC) and human iPSC-derived NPC...
June 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28636235/stem-cell-based-tooth-and-periodontal-regeneration
#9
Lei Hu, Yi Liu, Songlin Wang
Currently regeneration of tooth and periodontal damage still remains great challenge. Stem cell-based tissue engineering raised novel therapeutic strategies for tooth and periodontal repair. Stem cells for tooth and periodontal regeneration include dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), stem cells from the dental apical papilla (SCAPs), and stem cells from human exfoliated deciduous teeth (SHEDs), dental follicle stem cells (DFSCs), dental epithelial stem cells (DESCs), bone marrow mesenchymal stem cells (BMMSCs), adipose-derived stem cells (ADSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs)...
June 21, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28635509/induced-pluripotent-stem-cell-derived-dopaminergic-neurons-from-adult-common-marmoset-fibroblasts
#10
Scott C Vermilyea, Scott Guthrie, Michael Meyer, Kim Smuga-Otto, Katarina Braun, Sara Howden, James A Thomson, Su-Chun Zhang, Marina Emborg, Dr Thaddeus G Golos
The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter lifespan compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties including development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers...
June 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28635177/engineering-human-bone-grafts-with-new-macroporous-calcium-phosphate-cement-scaffolds
#11
Martina Sladkova, Michael Palmer, Caroline Öhman, Jiayi Cheng, Shoug Al-Ansari, Munerah Saad, Håkan Engqvist, Giuseppe Maria de Peppo
Bone engineering opens the possibility to grow large amounts of tissue products by combining patient-specific cells with compliant biomaterials. Decellularized tissue matrices represent suitable biomaterials but availability, long processing time, excessive cost, and concerns on pathogen transmission have led to the development of biomimetic synthetic alternatives. We recently fabricated calcium phosphate cement (CPC) scaffolds with variable macroporosity using a facile synthesis method with minimal manufacturing steps, and demonstrated long-term biocompatibility in vitro...
June 21, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28634935/generation-of-induced-pluripotent-stem-cells-in-defined-three-dimensional-hydrogels
#12
Massimiliano Caiazzo, Yoji Tabata, Matthias Lutolf
Since the groundbreaking discovery of induced pluripotent stem cells (iPSCs) many research groups have attempted to improve the efficiency of the classical cell reprogramming process. Surprisingly, the contribution of the three-dimensional (3D) microenvironment to iPSC generation has been largely overlooked. Here we describe a protocol for the generation of iPSCs in defined poly(ethylene glycol) (PEG)-based hydrogels that, besides allowing higher reprogramming efficiency, are also a powerful tool to study the influence of biophysical parameters on iPSC generation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28628273/exposure-of-induced-pluripotent-stem-cell-derived-vascular-endothelial-and-smooth-muscle-cells-in-coculture-to-hemodynamics-induces-primary-vascular-cell-like-phenotypes
#13
Maria S Collado, Banumathi K Cole, Robert A Figler, Mark Lawson, David Manka, Michael B Simmers, Steve Hoang, Felipe Serrano, Brett R Blackman, Sanjay Sinha, Brian R Wamhoff
Human induced pluripotent stem cells (iPSCs) can be differentiated into vascular endothelial (iEC) and smooth muscle (iSMC) cells. However, because iECs and iSMCs are not derived from an intact blood vessel, they represent an immature phenotype. Hemodynamics and heterotypic cell:cell communication play important roles in vascular cell phenotypic modulation. Here we tested the hypothesis that hemodynamic exposure of iECs in coculture with iSMCs induces an in vivo-like phenotype. iECs and iSMCs were cocultured under vascular region-specific blood flow hemodynamics, and compared to hemodynamic cocultures of blood vessel-derived endothelial (pEC) and smooth muscle (pSMC) cells...
June 19, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28628110/colonic-organoids-derived-from-human-induced-pluripotent-stem-cells-for-modeling-colorectal-cancer-and-drug-testing
#14
Miguel Crespo, Eduardo Vilar, Su-Yi Tsai, Kyle Chang, Sadaf Amin, Tara Srinivasan, Tuo Zhang, Nina H Pipalia, Huanhuan Joyce Chen, Mavee Witherspoon, Miriam Gordillo, Jenny Zhaoying Xiang, Frederick R Maxfield, Steven Lipkin, Todd Evans, Shuibing Chen
With the goal of modeling human disease of the large intestine, we sought to develop an effective protocol for deriving colonic organoids (COs) from differentiated human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Extensive gene and immunohistochemical profiling confirmed that the derived COs represent colon rather than small intestine, containing stem cells, transit-amplifying cells, and the expected spectrum of differentiated cells, including goblet and endocrine cells. We applied this strategy to iPSCs derived from patients with familial adenomatous polyposis (FAP-iPSCs) harboring germline mutations in the WNT-signaling-pathway-regulator gene encoding APC, and we generated COs that exhibit enhanced WNT activity and increased epithelial cell proliferation, which we used as a platform for drug testing...
June 19, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28627367/nrf2-pathway-activation-upon-rotenone-treatment-in-human-ipsc-derived-neural-stem-cells-undergoing-differentiation-towards-neurons-and-astrocytes
#15
Francesca Pistollato, David Canovas-Jorda, Dimitra Zagoura, Anna Bal-Price
Activation of Nrf2/ARE signaling pathway occurs ubiquitously in most cell types upon induction of oxidative stress. Rotenone, an inhibitor of mitochondrial complex I, can be used to trigger oxidative stress, stimulate the activation of Nrf2 pathway in neuronal and astrocytic cells and assess neurotoxicity. We have previously demonstrated that an acute treatment with rotenone can induce Nrf2 activation, which leads to astrocyte activation and dopaminergic (DA) neuronal cell death in a mixed neuronal/astrocytic cell model derived from human induced pluripotent stem cells (hiPSCs)...
June 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28627365/mitochondria-metabolic-reprogramming-in-the-formation-of-neurons-from-peripheral-cells-cause-or-consequence-and-the-implications-to-their-utility
#16
REVIEW
Gary E Gibson, Ankita Thakkar
The induction of pluripotent stem cells (iPSC) from differentiated cells such as fibroblasts and their subsequent conversion to neural progenitor cells (NPC) and finally to neurons is intriguing scientifically, and its potential to medicine nearly infinite, but unrealized. A better understanding of the changes at each step of the transformation will enable investigators to use them better to model neurological disease. Each step of conversion from a differentiated cell to an iPSC to a NPC to neurons requires large changes in glycolysis including aerobic glycolysis, the pentose shunt, the tricarboxylic acid cycle, the electron transport chain and in the production of reactive oxygen species (ROS)...
June 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28626459/the-immunogenicity-and-immune-tolerance-of-pluripotent-stem-cell-derivatives
#17
REVIEW
Xin Liu, Wenjuan Li, Xuemei Fu, Yang Xu
Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and differentiate into all cell types in human body, and therefore hold great potential for cell therapy of currently incurable diseases including neural degenerative diseases, heart failure, and macular degeneration. This potential is further underscored by the promising safety and efficacy data from the ongoing clinical trials of hESC-based therapy of macular degeneration. However, one main challenge for the clinical application of hESC-based therapy is the allogeneic immune rejection of hESC-derived cells by the recipient...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28626364/ex-vivo-generation-of-genetically-modified-macrophages-from-human-induced-pluripotent-stem-cells
#18
Mania Ackermann, Alexandra Kuhn, Jessica Kunkiel, Sylvia Merkert, Ulrich Martin, Thomas Moritz, Nico Lachmann
BACKGROUND: Pluripotent stem cells, including induced pluripotent stem cells (iPSCs), have the capacity to differentiate towards all three germ layers and have been highlighted as an attractive cell source for the field of regenerative medicine. Thus, stable expression of therapeutic transgenes in iPSCs, as well as thereof derived progeny of hematopoietic lineage, may lay the foundation for innovative cell replacement therapies. METHODS: We have utilized human iPSC lines genetically modified by lentiviral vector technology or targeted integration of reporter genes to evaluate transgene expression during hematopoietic specification and differentiation towards macrophages...
June 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28626363/hoxb4-increases-runx1-expression-to-promote-the-de-novo-formation-of-multipotent-hematopoietic-cells
#19
Nadine Teichweyde, Peter A Horn, Hannes Klump
BACKGROUND: The de novo generation of patient-specific hematopoietic stem and progenitor cells from induced pluripotent stem cells (iPSCs) has become a promising approach for cell replacement therapies in the future. However, efficient differentiation protocols for producing fully functional human hematopoietic stem cells are still missing. In the mouse model, ectopic expression of the human homeotic selector protein HOXB4 has been shown to enforce the development of hematopoietic stem cells (HSCs) in differentiating pluripotent stem cell cultures...
June 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28625609/oxidative-stress-induced-by-cumene-hydroperoxide-produces-synaptic-depression-and-transient-hyperexcitability-in-rat-primary-motor-cortex-neurons
#20
R Pardillo-Diaz, L Carrascal, G Barrionuevo, P Nunez-Abades
Pyramidal neurons of the motor cortex are selectively degenerated in Amyotrophic Lateral Sclerosis (ALS). The mechanisms underlying neuronal death in ALS are not well established. In the absence of useful biomarkers, the early increased neuronal excitability seems to be the unique characteristic of ALS. Lipid peroxidation caused by oxidative stress has been postulated as one of the possible mechanisms involved in degeneration motor cortex pyramidal neurons. This paper examines the effect of lipid peroxidation on layer V pyramidal neurons induced by cumene hydroperoxide (CH) in brain slices from wild type rats...
June 15, 2017: Molecular and Cellular Neurosciences
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