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Epigenetics regenerative medicine

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https://www.readbyqxmd.com/read/30108462/ectopic-micrornas-used-to-preserve-human-mesenchymal-stem-cell-potency-and-epigenetics
#1
Navid Ghasemzadeh, Fatemeh Pourrajab, Ali Dehghani Firoozabadi, Seyedhossein Hekmatimoghaddam, Fatemeh Haghiralsadat
Human mesenchymal stem cells (hMSCs) have remarkable potential for use in regenerative medicine. However, one of the great challenges is preserving their potency for long time. This study investigated the effect of miRNA ectopic expression on their proliferation and also on the expression level of Parp1 as an epigenetic switch preserving pluripotency in hMSCs. A cationic liposome was prepared as an efficient carrier for miRNA delivery. The miRNA loading efficiency and physical stability of vesicles were measured, and their scanning electron microscopic shapes determined...
2018: EXCLI Journal
https://www.readbyqxmd.com/read/30077989/gene-editing-for-inflammatory-disorders
#2
REVIEW
David T Ewart, Erik J Peterson, Clifford J Steer
Technology for precise and efficient genetic editing is constantly evolving and is now capable of human clinical applications. Autoimmune and inflammatory diseases are chronic, disabling, sometimes life-threatening, conditions that feature heritable components. Both primary genetic lesions and the inflammatory pathobiology underlying these diseases represent fertile soil for new therapies based on the capabilities of gene editing. The ability to orchestrate precise targeted modifications to the genome will likely enable cell-based therapies for inflammatory diseases such as monogenic autoinflammatory disease, acquired autoimmune disease and for regenerative medicine in the setting of an inflammatory environment...
August 4, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/30077716/neural-stem-cell-differentiation-to-mature-neurons-mechanisms-of-regulation-and-biotechnological-applications
#3
REVIEW
Mariana S Vieira, Anderson K Santos, Rebecca Vasconcellos, Vânia A M Goulart, Ricardo C Parreira, Alexandre H Kihara, Henning Ulrich, Rodrigo R Resende
The abilities of stem cells to self-renew and form different mature cells expand the possibilities of applications in cell-based therapies such as tissue recomposition in regenerative medicine, drug screening, and treatment of neurodegenerative diseases. In addition to stem cells found in the embryo, various adult organs and tissues have niches of stem cells in an undifferentiated state. In the central nervous system of adult mammals, neurogenesis occurs in two regions: the subventricular zone and the dentate gyrus in the hippocampus...
August 2, 2018: Biotechnology Advances
https://www.readbyqxmd.com/read/29989289/unveiling-epigenetic-regulation-in-cancer-aging-and-rejuvenation-with-in-vivo-reprogramming-technology
#4
Yuko Sogabe, Hiroshi Seno, Takuya Yamamoto, Yasuhiro Yamada
Reprogramming technology has enabled the fate conversion of terminally differentiated somatic cells into pluripotent stem cells or into another differentiated state. A dynamic reorganization of epigenetic regulation takes place during cellular reprogramming. Given that reprogramming does not require changes in the underlying genome, the technology can be used to actively modify epigenetic regulation. Although reprogramming has been investigated mostly at the cellular level in vitro, studies have demonstrated that somatic cells are reprogrammable in multicellular organisms in vivo...
July 10, 2018: Cancer Science
https://www.readbyqxmd.com/read/29972931/-topographies-of-biomaterials-regulate-cell-functions-under-epigenetic-mechanisms
#5
Y S Zhou
Topographies of biomaterials can act as potent regulators of cell functions, including proliferation, migration, differentiation, and reprograming. The mechanisms involve not only signaling pathways, but also epigenetic regulations. A clearer picture of how topographies of biomaterials alter epigenetic states facilitates the design of highly-functionalized and individualized biomaterials, and provides novel insights into epigenetic manipulation in controlling cell fates in regenerative medicine and disease treatment...
October 9, 2017: Zhonghua Kou Qiang Yi Xue za Zhi, Zhonghua Kouqiang Yixue Zazhi, Chinese Journal of Stomatology
https://www.readbyqxmd.com/read/29967137/synthetic-far-red-light-mediated-crispr-dcas9-device-for-inducing-functional-neuronal-differentiation
#6
Jiawei Shao, Meiyan Wang, Guiling Yu, Sucheng Zhu, Yuanhuan Yu, Boon Chin Heng, Jiali Wu, Haifeng Ye
The ability to control the activity of CRISPR-dCas9 with precise spatiotemporal resolution will enable tight genome regulation of user-defined endogenous genes for studying the dynamics of transcriptional regulation. Optogenetic devices with minimal phototoxicity and the capacity for deep tissue penetration are extremely useful for precise spatiotemporal control of cellular behavior and for future clinic translational research. Therefore, capitalizing on synthetic biology and optogenetic design principles, we engineered a far-red light (FRL)-activated CRISPR-dCas9 effector (FACE) device that induces transcription of exogenous or endogenous genes in the presence of FRL stimulation...
July 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29939183/chemical-reversion-of-conventional-human-pluripotent-stem-cells-to-a-na%C3%A3-ve-like-state-with-improved-multilineage-differentiation-potency
#7
Tea Soon Park, Ludovic Zimmerlin, Rebecca Evans-Moses, Elias T Zambidis
Naïve human pluripotent stem cells (N-hPSC) with improved functionality may have a wide impact in regenerative medicine. The goal of this protocol is to efficiently revert lineage-primed, conventional human pluripotent stem cells (hPSC) maintained on either feeder-free or feeder-dependent conditions to a naïve-like pluripotency with improved functionality. This chemical naïve reversion method employs the classical leukemia inhibitory factor (LIF), GSK3β, and MEK/ERK inhibition cocktail (LIF-2i), supplemented with only a tankyrase inhibitor XAV939 (LIF-3i)...
June 10, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29852072/editing-the-epigenome-reshaping-the-genomic-landscape
#8
Liad Holtzman, Charles A Gersbach
The eukaryotic epigenome has an instrumental role in determining and maintaining cell identity and function. Epigenetic components such as DNA methylation, histone tail modifications, chromatin accessibility, and DNA architecture are tightly correlated with central cellular processes, while their dysregulation manifests in aberrant gene expression and disease. The ability to specifically edit the epigenome holds the promise of enhancing understanding of how epigenetic modifications function and enabling manipulation of cell phenotype for research or therapeutic purposes...
May 31, 2018: Annual Review of Genomics and Human Genetics
https://www.readbyqxmd.com/read/29845793/metabolic-signature-of-pluripotent-stem-cells
#9
Sara Taleahmad, Seyedeh Nafiseh Hassani, Ghasem Hosseini Salekdeh, Hossein Baharvand
Objective: Pluripotent stem cells (PSCs), with the capacity to self-renew and differentiate into all other cell types, are of benefit in regenerative medicine applications. Tightly controlled gene expression networks and epigenetic factors regulate these properties. In this study, we aim to evaluate the metabolic signature of pluripotency under 2i and R2i culture conditions versus serum condition. Materials and Methods: In this experimental study, we investigated bioinformatics analysis of the shotgun proteomics data for cells grown under 2i, R2i, and serum culture conditions...
October 2018: Cell Journal
https://www.readbyqxmd.com/read/29786549/pluripotent-stem-cells-induction-and-self-renewal
#10
REVIEW
R Abu-Dawud, N Graffmann, S Ferber, W Wruck, J Adjaye
Pluripotent stem cells (PSCs) lie at the heart of modern regenerative medicine due to their properties of unlimited self-renewal in vitro and their ability to differentiate into cell types representative of the three embryonic germ layers-mesoderm, ectoderm and endoderm. The derivation of induced PSCs bypasses ethical concerns associated with the use of human embryonic stem cells and also enables personalized cell-based therapies. To exploit their regenerative potential, it is essential to have a firm understanding of the molecular processes associated with their induction from somatic cells...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29669575/effects-of-senolytic-drugs-on-human-mesenchymal-stromal-cells
#11
Clara Grezella, Eduardo Fernandez-Rebollo, Julia Franzen, Mónica Sofia Ventura Ferreira, Fabian Beier, Wolfgang Wagner
BACKGROUND: Senolytic drugs are thought to target senescent cells and might thereby rejuvenate tissues. In fact, such compounds were suggested to increase health and lifespan in various murine aging models. So far, effects of senolytic drugs have not been analysed during replicative senescence of human mesenchymal stromal cells (MSCs). METHODS: In this study, we tested four potentially senolytic drugs: ABT-263 (navitoclax), quercetin, nicotinamide riboside, and danazol...
April 18, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29653249/directing-neuronal-cell-fate-in-vitro-achievements-and-challenges
#12
REVIEW
R J M Riemens, D L A van den Hove, M Esteller, R Delgado-Morales
Human pluripotent stem cell (PSC) technology and direct somatic cell reprogramming have opened up a promising new avenue in the field of neuroscience. These recent advances allow researchers to obtain virtually any cell type found in the human brain, making it possible to produce and study functional neurons in laboratory conditions for both scientific and medical purposes. Although distinct approaches have shown to be successful in directing neuronal cell fate in vitro, their refinement and optimization, as well as the search for alternative approaches, remains necessary to help realize the full potential of the eventually derived neuronal populations...
April 10, 2018: Progress in Neurobiology
https://www.readbyqxmd.com/read/29626316/comparative-in-silico-profiling-of-epigenetic-modifiers-in-human-tissues
#13
Mi-Young Son, Cho-Rok Jung, Dae-Soo Kim, Hyun-Soo Cho
The technology of tissue differentiation from human pluripotent stem cells has attracted attention as a useful resource for regenerative medicine, disease modeling and drug development. Recent studies have suggested various key factors and specific culture methods to improve the successful tissue differentiation and efficient generation of human induced pluripotent stem cells. Among these methods, epigenetic regulation and epigenetic signatures are regarded as an important hurdle to overcome during reprogramming and differentiation...
June 2018: Molecular Biology Reports
https://www.readbyqxmd.com/read/29576745/anti-inflamm-ageing-and-or-anti-age-related-disease-emerging-treatments-a-historical-alchemy-or-revolutionary-effective-procedures
#14
REVIEW
Carmela Rita Balistreri
The " long-life elixir " has long represented for humans a dream, a vanity's sin for remaining young and to long survive. Today, because of ageing population phenomenon , the research of antiageing interventions appears to be more important than ever, for preserving health in old age and retarding/or delaying the onset of age-related diseases. A hope is given by experimental data, which evidence the possibility of retarding ageing in animal models. In addition, it has been also demonstrated in animal life-extending studies not only the possibility of increasing longevity but also the ability to retard the onset of age-related diseases...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29564301/trans-differentiation-via-epigenetics-a-new-paradigm-in-the-bone-regeneration
#15
REVIEW
Young-Dan Cho, Hyun-Mo Ryoo
In regenerative medicine, growing cells or tissues in the laboratory is necessary when damaged cells can not heal by themselves. Acquisition of the required cells from the patient's own cells or tissues is an ideal option without additive side effects. In this context, cell reprogramming methods, including the use of induced pluripotent stem cells (iPSCs) and trans-differentiation, have been widely studied in regenerative research. Both approaches have advantages and disadvantages, and the possibility of de-differentiation because of the epigenetic memory of iPSCs has strengthened the need for controlling the epigenetic background for successful cell reprogramming...
February 2018: Journal of Bone Metabolism
https://www.readbyqxmd.com/read/29500792/safety-and-efficacy-of-epigenetically-converted-human-fibroblasts-into-insulin-secreting-cells-a-preclinical-study
#16
Tiziana A L Brevini, Georgia Pennarossa, Elena F M Manzoni, Fulvio Gandolfi
Type 1 Diabetes Mellitus (T1DM) is a chronic disease that leads to loss of insulin secreting β-cells, causing high levels of blood glucose. Exogenous insulin administration is not sufficient to mimic the normal function of β-cells and, consequently, diabetes mellitus often progresses and can lead to major chronic complications and morbidity. The physiological control of glucose levels can only be restored by replacing the β-cell mass.We recently developed a new strategy that allows for epigenetic conversion of dermal fibroblasts into insulin-secreting cells (EpiCC), using a brief exposure to the demethylating agent 5-aza-cytidine (5-aza-CR), followed by a pancreatic induction protocol...
March 3, 2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29464084/lysine-specific-demethylase-1-inhibitors-prevent-teratoma-development-from-human-induced-pluripotent-stem-cells
#17
Naoki Osada, Jiro Kikuchi, Takashi Umehara, Shin Sato, Masashi Urabe, Tomoyuki Abe, Nakanobu Hayashi, Masahiko Sugitani, Yutaka Hanazono, Yusuke Furukawa
Human induced pluripotent stem cells (hiPSCs) are creating great expectations for regenerative medicine. However, safety strategies must be put in place to guard against teratoma formation after transplantation of hiPSC-derived cells into patients. Recent studies indicate that epigenetic regulators act at the initial step of tumorigenesis. Using gain-of-function and loss-of-function approaches, we show here that the expression and function of lysine-specific demethylase 1 (LSD1) are tightly regulated in hiPSCs, and their deregulation underlies the development of teratomas...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29423397/age-is-relative-impact-of-donor-age-on-induced-pluripotent-stem-cell-derived-cell-functionality
#18
REVIEW
Elisabeth Tamara Strässler, Katriina Aalto-Setälä, Mostafa Kiamehr, Ulf Landmesser, Nicolle Kränkel
Induced pluripotent stem cells (iPSCs) avoid many of the restrictions that hamper the application of human embryonic stem cells: limited availability of source material due to legal restrictions in some countries, immunogenic rejection and ethical concerns. Also, the donor's clinical phenotype is often known when working with iPSCs. Therefore, iPSCs seem ideal to tackle the two biggest tasks of regenerative medicine: degenerative diseases with genetic cause (e.g., Duchenne's muscular dystrophy) and organ replacement in age-related diseases (e...
2018: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29356242/preferable-in-vitro-condition-for-maintaining-faithful-dna-methylation-imprinting-in-mouse-embryonic-stem-cells
#19
Jiyoung Lee, Ayumi Matsuzawa, Hirosuke Shiura, Akito Sutani, Fumitoshi Ishino
Epigenetic properties of cultured embryonic stem cells (ESCs), including DNA methylation imprinting, are important because they affect the developmental potential. Here, we tested a variety of culture media, including knockout serum replacement (KSR) and fetal bovine serum (FBS) with or without inhibitors of Gsk3β and Mek1/2 (2i) at various time points. In addition to the previously known passage-dependent global changes, unexpected dynamic DNA methylation changes occurred in both maternal and paternal differentially methylated regions: under the widely used condition of KSR with 2i, a highly hypomethylated state occurred at early passages (P1-7) as well as P10, but DNA methylation increased over further passages in most conditions, except under KSR with 2i at P25...
March 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/29353456/in-vivo-transient-and-partial-cell-reprogramming-to-pluripotency-as-a-therapeutic-tool-for-neurodegenerative-diseases
#20
REVIEW
S Tamanini, G P Comi, S Corti
In theory, human diseases in which a specific cell type degenerates, such as neurodegenerative diseases, can be therapeutically addressed by replacement of the lost cells. The classical strategy for cell replacement is exogenous cell transplantation, but now, cell replacement can also be achieved with in situ reprogramming. Indeed, many of these disorders are age-dependent, and "rejuvenating" strategies based on cell epigenetic modifications are a possible approach to counteract disease progression...
August 2018: Molecular Neurobiology
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