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Epigenetics regenerative medicine

Raheleh Farahzadi, Ezzatollah Fathi, Seyed Alireza Mesbah-Namin, Nosratollah Zarghami
The identification of factors that reduce the senescent tendency of the mesenchymal stem cells (MSCs) upon expansion has great potential for cellular therapies in regenerative medicine. Previous studies have shown the aging protective effect of L-carnitine (LC). On the other hand, reduction in proliferation potential and age-dependent decline in number and functions of MSCs were accompanied by telomere shortening, reduction in telomerase activity and epigenetic changes. The aim of this study was to evaluate the effects of LC on aging of MSCs through telomerase activity assessment and the investigation of methylation status of the hTERT gene promoter...
October 2018: Tissue & Cell
Mohamed I Gatie, Gregory M Kelly
Glucose metabolism has a crucial role for providing substrates required to generate ATP and regulate the epigenetic landscape. We reported that F9 embryonal carcinoma stem-like cells require cytosolic reactive oxygen species to differentiate into extraembryonic endoderm; however, mitochondrial sources were not examined. To extend these studies, we examined the metabolic profile of early and late-passage F9 cells, and show that their ability to differentiate is similar, even though each population has dramatically different metabolic profiles...
2018: Cell Death Discovery
Shigeo Saito, Ying-Chu Lin, Yukio Nakamura, Richard Eckner, Kenly Wuputra, Kung-Kai Kuo, Chang-Shen Lin, Kazunari K Yokoyama
The ability to control the transition from an undifferentiated stem cell to a specific cell fate is one of the key techniques that are required for the application of interventional technologies to regenerative medicine and the treatment of tumors and metastases and of neurodegenerative diseases. Reprogramming technologies, which include somatic cell nuclear transfer, induced pluripotent stem cells, and the direct reprogramming of specific cell lineages, have the potential to alter cell plasticity in translational medicine for cancer treatment...
October 3, 2018: Cellular and Molecular Life Sciences: CMLS
Yungang Xu, Weiling Zhao, Scott D Olson, Karthik S Prabhakara, Xiaobo Zhou
BACKGROUND: Understanding the embryonic stem cell (ESC) fate decision between self-renewal and proper differentiation is important for developmental biology and regenerative medicine. Attention has focused on mechanisms involving histone modifications, alternative pre-messenger RNA splicing, and cell-cycle progression. However, their intricate interrelations and joint contributions to ESC fate decision remain unclear. RESULTS: We analyze the transcriptomes and epigenomes of human ESC and five types of differentiated cells...
September 14, 2018: Genome Biology
Fan Zhou, Qingqing Yuan, Wenhui Zhang, Minghui Niu, Hongyong Fu, Qianqian Qiu, Guoping Mao, Hong Wang, Liping Wen, Hongxiang Wang, Mujun Lu, Zheng Li, Zuping He
Human spermatogonial stem cells (SSCs) could have significant applications in reproductive medicine and regenerative medicine because of their great plasticity. The fate determinations of human SSCs are mediated by epigenetic factors. However, nothing is known about the regulation of non-coding RNA on human SSCs. Here we have explored for the first time the expression, function, and target of miR-663a in human SSCs. MiR-663a was upregulated in human spermatogonia compared with pachytene spermatocytes, as indicated by microRNA microarray and real-time PCR...
September 7, 2018: Molecular Therapy. Nucleic Acids
Alessandra Ferrari, Raffaella Longo, Rui Silva, Nico Mitro, Donatella Caruso, Emma De Fabiani, Maurizio Crestani
In the last decade numerous publications highlighted the connection between metabolism and epigenetics in different physiological and pathological conditions. The availability of metabolites for cells represents indeed a crucial factor, which is able to condition cell fate and development, differentiation and proliferation partially trough epigenetic control. This tight link provides novel therapeutic possibilities to treat many pathological conditions induced by epigenetic alterations, by manipulating metabolic pathways producing metabolites that work also as epigenetic modifiers...
August 17, 2018: Pharmacology & Therapeutics
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
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
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...
November 15, 2018: Biotechnology Advances
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 reported that somatic cells are reprogrammable in multicellular organisms in vivo...
September 2018: Cancer Science
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
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
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
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...
August 31, 2018: Annual Review of Genomics and Human Genetics
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
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
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
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...
September 2018: Progress in Neurobiology
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
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
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