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Epigenetics regenerative medicine

Monika Gasiūnienė, Anastasija Zubova, Algirdas Utkus, Rūta Navakauskienė
Human amniotic fluid-derived mesenchymal stem cells (AF-MSCs) may be a valuable source for cell therapy and regenerative medicine. In this study, the potential of DNA methyltransferases (DNMT) inhibitors Decitabine, Zebularine, RG108 alone or combined with Zebularine and p53 inhibitor Pifithrin-α to induce cardiomyogenic differentiation of AF-MSCs was investigated. Differentiation into cardiomyocyte-like cells initiation was indicated with all agents by changes in the cell phenotype, upregulation of the relative expression of the main cardiac genes (NKX2-5, TNNT2, MYH6, and DES) as well as of cardiac ion channels genes (sodium, calcium, and potassium) as determined by reverse-transcription quantitative polymerase chain reaction and the increase in Connexin43 levels as detected from Western blot and immunofluorescence data...
November 28, 2018: Journal of Cellular Biochemistry
E N Grigoryan
Modern achievements in the understanding of tissue regeneration, identification of endogenous cell sources for regeneration, and development of approaches for induction and differentiation of pluripotent stem cells have open broad prospects for regenerative medicine. However, application of the obtained information in medicine is hindered by insufficient knowledge on the molecular factors and their combinations capable of regulating the age and fate of cellular sources for eye tissue reparation as well as on the regenerative responses of these cells...
November 2018: Biochemistry. Biokhimii︠a︡
Veronica Astro, Antonio Adamo
The raising worldwide prevalence of Type 1 and Type 2 diabetes mellitus (T1DM and T2DM) solicits the derivation of in vitro methods yielding mature and fully functional β-cells to be used in regenerative medicine. Several protocols to differentiate human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) into human pancreatic β-like cells have recently been developed. These methods, coupled with a bioengineering approach using biocompatible encapsulating devices, have recently led to experimental clinical trials showing great promises to ultimately end the battle of diabetic patients for managing hyperglycemia...
2018: Frontiers in Cell and Developmental Biology
Abhisek Mitra, Jun Yan, Liangfang Zhang, Shulin Li
Liver is the second most transplanted organ according to United network for organ sharing. Due to shortage of compatible donors, surgical difficulties, immunological hindrance, and high postoperative cost, stem cell therapy is an attractive substitute of liver transplant for millions of patients suffering from hepatic failure. Due to several technical limitations such as viral integration, inefficient differentiation, and adult phenotypes and epigenetic memory of fibroblasts, induced pluripotent stem cells, mesenchymal stem cells, or induced hepatocyte may not present a great clinical substitute for liver transplant...
October 19, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
Anandika Dhaliwal, Sandra Pelka, David S Gray, Prabhas V Moghe
Stem cells are considered as a multipotent regenerative source for diseased and dysfunctional tissues. Despite the promise of stem cells, the inherent capacity of stem cells to convert to tissue-specific lineages can present a major challenge to the use of stem cells for regenerative medicine. We hypothesized that epigenetic regulating molecules can modulate the stem cell's developmental program, and thus potentially overcome the limited lineage differentiation that human stem cells exhibit based on the source and processing of stem cells...
November 2, 2018: Scientific Reports
Francesca Diomede, Nicoletta Zini, Jacopo Pizzicannella, Ilaria Merciaro, Giuseppe Pizzicannella, Monica D'Orazio, Adriano Piattelli, Oriana Trubiani
Embryoid bodies (EBs) are three-dimensional aggregates formed by pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells. They are used as an in vitro model to evaluate early extraembryonic tissue formation and differentiation process. In the adult organisms, cell differentiation is controlled and realized through the epigenetic regulation of gene expression, which consists of various mechanisms including DNA methylation. One demethylating agent is represented by 5-Azacytidine (5-Aza), considered able to induce epigenetic changes through gene derepression...
2018: Frontiers in Genetics
Nikhil Jain, Viola Vogel
Macrophages respond to chemical/metabolic and physical stimuli, but their effects cannot be readily decoupled in vivo during pro-inflammatory activation. Here, we show that preventing macrophage spreading by spatial confinement, as imposed by micropatterning, microporous substrates or cell crowding, suppresses late lipopolysaccharide (LPS)-activated transcriptional programs (biomarkers IL-6, CXCL9, IL-1β, and iNOS) by mechanomodulating chromatin compaction and epigenetic alterations (HDAC3 levels and H3K36-dimethylation)...
October 22, 2018: Nature Materials
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
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