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Epigenetics regenerative medicine

Miaoying Yu, Yinghui Wei, Kui Xu, Shasha Liu, Lei Ma, Yangli Pei, Yanqing Hu, Zhiguo Liu, Xue Zhang, Bingyuan Wang, Yulian Mu, Kui Li
Background: Self-renewal and pluripotency are considered as unwavering features of embryonic stem cells (ESCs). How ESCs regulate the self-renewal and differentiation is a central question in development and regenerative medicine research. Epidermal growth factor receptor (EGFR) was identified as a critical regulator in embryonic development, but its role in the maintenance of ESCs is poorly understood. Methods: Here, EGFR was disrupted by its specific inhibitor AG1478 in mouse ESCs (mESCs), and its self-renewal and pluripotency were characterized according to their proliferation, expression of pluripotency markers, embryoid body (EB) formation, and mRNA expression patterns...
2019: PeerJ
Fabrizio Gallo, Gaetano Ninotta, Maurizio Schenone, Pierluigi Cortese, Claudio Giberti
Among the several options that have been proposed in recent years for the management of male stress urinary incontinence (SUI), stem cell therapy represents a new frontier in treatment. The aim of this paper is to update the current status of stem cell therapy in animal and human studies for the management of iatrogenic male SUI. Areas covered: A literature review was conducted based on MEDLINE/PubMed searches for English articles using a combination of the following keywords: stem cell therapy, urinary incontinence, prostatectomy, regenerative medicine, mesenchymal stem cells...
February 1, 2019: Expert Opinion on Biological Therapy
Luminita Labusca, Kaveh Mashayekhi
Cellular reprogramming and induced pluripotent stem cell (IPSC) technology demonstrated the plasticity of adult cell fate, opening a new era of cellular modelling and introducing a versatile therapeutic tool for regenerative medicine. While IPSCs are already involved in clinical trials for various regenerative purposes, critical questions concerning their medium- and long-term genetic and epigenetic stability still need to be answered. Pluripotent stem cells have been described in the last decades in various mammalian and human tissues (such as bone marrow, blood and adipose tissue)...
January 26, 2019: World Journal of Stem Cells
Monika Glemžaitė, Aistė Zentelytė, Bartosz Wojtas, Sandra Baronaitė, Natalija Krasovskaja, Jūratė Savickienė, Bartlomiej Gielniewski, Bozena Kaminska, Algirdas Utkus, Rūta Navakauskienė
Human amniotic fluid-derived mesenchymal stem cells (AF-MSCs) are a new potential stem cell source for cell therapy and regenerative medicine. These are fetal mesenchymal stem cells with multi-lineage differentiation potential found in amniotic fluid. The aim of the present study was to evaluate in vitro differentiation initiation of AF-MSCs into cardiac progenitors upon application of inhibitors of DNA methyltransferases (DNMT), such as Decitabine (5-aza-2'-deoxycytidine) and Zebularine. We assessed epigenetic changes and explored patterns of genes, enriched in association with hyperacetylated H4 after induced differentiation...
January 13, 2019: Journal of Tissue Engineering and Regenerative Medicine
Monika Gasiūnienė, Aistė Zentelytė, Gražina Treigytė, Sandra Baronaitė, Jūratė Savickienė, Algirdas Utkus, Rūta Navakauskienė
Amniotic fluid-derived mesenchymal stem cells (AF-MSCs) are autologous to the fetus and represent a potential alternative source for the regenerative medicine and treatment of perinatal disorders. To date, AF-MSCs differentiation capacity to non-mesodermal lineages and epigenetic regulation are still poorly characterized. The present study investigated the differentiation potential of AF-MSCs towards neural-like cells in comparison to the mesodermal myogenic lineage and assessed epigenetic factors involved in tissue-specific differentiation...
January 11, 2019: Cell Biology International
Stefano Giulitti, Marco Pellegrini, Irene Zorzan, Paolo Martini, Onelia Gagliano, Margherita Mutarelli, Michael Johannes Ziller, Davide Cacchiarelli, Chiara Romualdi, Nicola Elvassore, Graziano Martello
Induced pluripotent stem cells (iPSCs) are generated via the expression of the transcription factors OCT4 (also known as POU5F1), SOX2, KLF4 and cMYC (OSKM) in somatic cells. In contrast to murine naive iPSCs, conventional human iPSCs are in a more developmentally advanced state called primed pluripotency. Here, we report that human naive iPSCs (niPSCs) can be generated directly from fewer than 1,000 primary human somatic cells, without requiring stable genetic manipulation, via the delivery of modified messenger RNAs using microfluidics...
December 31, 2018: Nature Cell Biology
Yi Wang, Laura A Bannister, Soji Sebastian, Yevgeniya Le, Youssef Ismail, Candice Didychuk, Richard B Richardson, Farrah Flegal, Laura Paterson, Patrick Causey, Ali Fawaz, Heather Wyatt, Nicholas Priest, Dmitry Klokov
PURPOSE: Health risks associated with the exposure of humans to low-dose ionizing radiation are currently estimated using the Linear-No-Threshold model. Over the last few decades, however, this model has been widely criticized for inconsistency with a large body of experimental evidence. Substantial efforts have been made to delineate biological mechanisms and health related outcomes of low-dose radiation. These include a large DOE funded Low Dose program operated in the 2000s, as well as the EU funded programs, previously NOTE and DOREMI and currently MELODI...
December 24, 2018: International Journal of Radiation Biology
Prim B Singh, Andrew G Newman
Age reprogramming represents a novel method for generating patient-specific tissues for transplantation. It bypasses the de-differentiation/redifferentiation cycle that is characteristic of the induced pluripotent stem (iPS) and nuclear transfer-embryonic stem (NT-ES) cell technologies that drive current interest in regenerative medicine. Despite the obvious potential of iPS and NT-ES cell-based therapies, there are several problems that must be overcome before these therapies are safe and routine. As an alternative, age reprogramming aims to rejuvenate the specialized functions of an old cell without de-differentiation; age reprogramming does not require developmental reprogramming through an embryonic stage, unlike the iPS and NT-ES cell-based therapies...
December 20, 2018: Epigenetics & Chromatin
Xiaojun Zhu, Chenglu Xiao, Jing-Wei Xiong
The zebrafish is broadly used for investigating de novo organ regeneration, because of its strong regenerative potential. Over the past two decades of intense study, significant advances have been made in identifying both the regenerative cell sources and molecular signaling pathways in a variety of organs in adult zebrafish. Epigenetic regulation has gradually moved into the center-stage of this research area, aided by comprehensive work demonstrating that DNA methylation, histone modifications, chromatin remodeling complexes, and microRNAs are essential for organ regeneration...
December 14, 2018: Journal of Cardiovascular Development and Disease
Varun Bansal, Debojyoti De, Jieun An, Tong Mook Kang, Hyeon-Ju Jeong, Jong-Sun Kang, Kyeong Kyu Kim
Use of stem cells in regenerative medicine holds great promise in treating people suffering from various otherwise incurable ailments. Direct conversion of somatic cells to other lineages thereby bypassing the intermediate pluripotent state has enormous applicability with respect to time requirement for conversion as well as safety issues. Among various approaches, chemical induced cell conversion is safe yet effective, and the use of small molecules has thus increased greatly in recent years in regenerative fields due to easy applicability, efficient scalability, and consistent reproducibility...
December 6, 2018: Biomaterials
Miruna Mihaela Micheu, Alina Ioana Scarlatescu, Alexandru Scafa-Udriste, Maria Dorobantu
Despite significant progress in treating ischemic cardiac disease and succeeding heart failure, there is still an unmet need to develop effective therapeutic strategies given the persistent high-mortality rate. Advances in stem cell biology hold great promise for regenerative medicine, particularly for cardiac regeneration. Various cell types have been used both in preclinical and clinical studies to repair the injured heart, either directly or indirectly. Transplanted cells may act in an autocrine and/or paracrine manner to improve the myocyte survival and migration of remote and/or resident stem cells to the site of injury...
December 7, 2018: Cells
Hossein Nikzad, Hamed Sabzalipoor, Javad Amini Mahabadi, Elahe Seyedhosseini, Seyed Ehsan Enderami, Seyed Mohammad Gheibi Hayat, Amirhosein Sahebkar
New perspectives have been opened by advances in stem cell research for reproductive and regenerative medicine. Several different cell types can be differentiated from stem cells (SCs) under suitable in vitro and in vivo conditions. The differentiation of SCs into male germ cells has been reported by many groups. Due to their unlimited pluripotency and self-renewal, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can be used as valuable tools for drug delivery, disease modeling, developmental studies, and cell-based therapies in regenerative medicine...
December 10, 2018: Journal of Cellular Physiology
Koichiro Nishino, Yoshikazu Arai, Ken Takasawa, Masashi Toyoda, Mayu Yamazaki-Inoue, Tohru Sugawara, Hidenori Akutsu, Ken Nishimura, Manami Ohtaka, Mahito Nakanishi, Akihiro Umezawa
Human induced pluripotent stem cells (iPSCs) are established by introducing several reprogramming factors, such as OCT3/4, SOX2, KLF4, c-MYC. Because of their pluripotency and immortality, iPSCs are considered to be a powerful tool for regenerative medicine. To date, iPSCs have been established all over the world by various gene delivery methods. All methods induced high-quality iPSCs, but epigenetic analysis of abnormalities derived from differences in the gene delivery methods has not yet been performed. Here, we generated genetically matched human iPSCs from menstrual blood cells by using three kinds of vectors, i...
December 2018: Regenerative Therapy
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
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