Boosting the Cellular Potency of Embryonic Stem Cells by Spliceosome Targeting ✉ Wilfried A
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Biopolymeric Materials for Tissue Regeneration, Cell Manufacturing, and Drug Delivery
University of Arkansas, Fayetteville ScholarWorks@UARK Theses and Dissertations 5-2021 Biopolymeric Materials for Tissue Regeneration, Cell Manufacturing, and Drug Delivery David Alfonso Castilla-Casadiego University of Arkansas, Fayetteville Follow this and additional works at: https://scholarworks.uark.edu/etd Part of the Polymer and Organic Materials Commons, and the Polymer Science Commons Citation Castilla-Casadiego, D. A. (2021). Biopolymeric Materials for Tissue Regeneration, Cell Manufacturing, and Drug Delivery. Theses and Dissertations Retrieved from https://scholarworks.uark.edu/etd/3964 This Dissertation is brought to you for free and open access by ScholarWorks@UARK. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of ScholarWorks@UARK. For more information, please contact [email protected]. Biopolymeric Materials for Tissue Regeneration, Cell Manufacturing, and Drug Delivery A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Engineering with a concentration in Chemical Engineering by David Alfonso Castilla-Casadiego Atlantic University Bachelor of Science in Chemical Engineering, 2011 University of Puerto Rico – Mayagüez Campus Master of Science in Chemical Engineering, 2016 May 2021 University of Arkansas This dissertation is approved for recommendation to the Graduate Council. ____________________________________ Jorge L. Almodóvar-Montañez, Ph.D. Dissertation Director ____________________________________ _________________________________ -
Reinforcement of STAT3 Activity Reprogrammes Human Embryonic Stem Cells to Naive-Like Pluripotency
ARTICLE Received 17 Apr 2014 | Accepted 2 Apr 2015 | Published 13 May 2015 DOI: 10.1038/ncomms8095 OPEN Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive-like pluripotency Hongwei Chen1,2, Ire`ne Aksoy1,2,3, Fabrice Gonnot1,2, Pierre Osteil1,2, Maxime Aubry1,2, Claire Hamela1,2, Cloe´ Rognard1,2, Arnaud Hochard1,2, Sophie Voisin1,2,4, Emeline Fontaine1,2, Magali Mure1,2, Marielle Afanassieff1,2,4, Elouan Cleroux5, Sylvain Guibert5, Jiaxuan Chen3,Ce´line Vallot6, Herve´ Acloque7, Cle´mence Genthon7,Ce´cile Donnadieu7, John De Vos8,9, Damien Sanlaville10, Jean- Franc¸ois Gue´rin1,2, Michael Weber5, Lawrence W. Stanton3, Claire Rougeulle6, Bertrand Pain1,2,4, Pierre-Yves Bourillot1,2 & Pierre Savatier1,2 Leukemia inhibitory factor (LIF)/STAT3 signalling is a hallmark of naive pluripotency in rodent pluripotent stem cells (PSCs), whereas fibroblast growth factor (FGF)-2 and activin/nodal signalling is required to sustain self-renewal of human PSCs in a condition referred to as the primed state. It is unknown why LIF/STAT3 signalling alone fails to sustain pluripotency in human PSCs. Here we show that the forced expression of the hormone-dependent STAT3-ER (ER, ligand-binding domain of the human oestrogen receptor) in combination with 2i/LIF and tamoxifen allows human PSCs to escape from the primed state and enter a state char- acterized by the activation of STAT3 target genes and long-term self-renewal in FGF2- and feeder-free conditions. These cells acquire growth properties, a gene expression profile and an epigenetic landscape closer to those described in mouse naive PSCs. -
Characterization of Embryonic Stem Cell-Differentiated Cells As Mesenchymal Stem Cells
The University of Southern Mississippi The Aquila Digital Community Honors Theses Honors College Fall 12-2015 Characterization of Embryonic Stem Cell-Differentiated Cells as Mesenchymal Stem Cells Rachael N. Kuehn University of Southern Mississippi Follow this and additional works at: https://aquila.usm.edu/honors_theses Part of the Cell Biology Commons Recommended Citation Kuehn, Rachael N., "Characterization of Embryonic Stem Cell-Differentiated Cells as Mesenchymal Stem Cells" (2015). Honors Theses. 349. https://aquila.usm.edu/honors_theses/349 This Honors College Thesis is brought to you for free and open access by the Honors College at The Aquila Digital Community. It has been accepted for inclusion in Honors Theses by an authorized administrator of The Aquila Digital Community. For more information, please contact [email protected]. The University of Southern Mississippi Characterization of Embryonic Stem Cell-Differentiated Cells as Mesenchymal Stem Cells by Rachael Nicole Kuehn A Thesis Submitted to the Honors College of The University of Southern Mississippi in Partial Fulfillment of the Requirements for the Degree of Bachelor of Science in the Department of Biological Sciences December 2015 ii Approved by ______________________________ Yanlin Guo, Ph.D., Thesis Adviser Professor of Biological Sciences ______________________________ Shiao Y. Wang, Ph.D., Chair Department of Biological Sciences ______________________________ Ellen Weinauer, Ph.D., Dean Honors College iii ABSTRACT Embryonic stem cells (ESCs), due to their ability to differentiate into different cell types while still maintaining a high proliferation capacity, have been considered as a potential cell source in regenerative medicine. However, current ESC differentiation methods are low yielding and create heterogeneous cell populations. -
Selecting Antagonistic Antibodies That Control Differentiation Through Inducible Expression in Embryonic Stem Cells
Selecting antagonistic antibodies that control differentiation through inducible expression in embryonic stem cells Anna N. Melidonia,1, Michael R. Dysonb, Sam Wormaldc,2, and John McCaffertya,b,3 aDepartment of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom; bIONTAS Ltd., Cambridge CB2 1QW, United Kingdom; and cThe Wellcome Trust Sanger Institute, Hinxton Cambs CB10 1SA, United Kingdom Edited* by Richard A. Lerner, The Scripps Research Institute, La Jolla, CA, and approved August 27, 2013 (received for review June 26, 2013) Antibodies that modulate receptor function have great untapped (5). In an alternative approach, antibodies were retained at the cell potential in the control of stem cell differentiation. In contrast to surface of BaF3 reporter cells, leading to the identification of an many natural ligands, antibodies are stable, exquisitely specific, agonistic antibody to the granulocyte colony-stimulating receptor (6). and are unaffected by the regulatory mechanisms that act on Pluripotent embryonic stem cells (ES cells) represent an ideal natural ligands. Here we describe an innovative system for reporter cell system for identifying functional antibodies because identifying such antibodies by introducing and expressing anti- they are poised to differentiate into many different cell types in body gene populations in ES cells. Following induced antibody vitro (7). ES cell fate decisions are influenced by a wide range of expression and secretion, changes in differentiation outcomes of cell-surface receptors (7–9), creating the potential to target many individual antibody-expressing ES clones are monitored using lin- different classes of ligands and receptors (e.g., receptor tyrosine fi eage-speci c gene expression to identify clones that encode and kinases, G protein-coupled receptors, ion channels, integrins, and express signal-modifying antibodies. -
A Concise Review on the Classification and Nomenclature of Stem Cells Kök Hücrelerinin S›N›Fland›R›Lmas› Ve Isimlendirilmesine Iliflkin K›Sa Bir Derleme
Review 57 A concise review on the classification and nomenclature of stem cells Kök hücrelerinin s›n›fland›r›lmas› ve isimlendirilmesine iliflkin k›sa bir derleme Alp Can Ankara University Medical School, Department of Histology and Embryology, Ankara, Turkey Abstract Stem cell biology and regenerative medicine is a relatively young field. However, in recent years there has been a tremen- dous interest in stem cells possibly due to their therapeutic potential in disease states. As a classical definition, a stem cell is an undifferentiated cell that can produce daughter cells that can either remain a stem cell in a process called self-renew- al, or commit to a specific cell type via the initiation of a differentiation pathway leading to the production of mature progeny cells. Despite this acknowledged definition, the classification of stem cells has been a perplexing notion that may often raise misconception even among stem cell biologists. Therefore, the aim of this brief review is to give a conceptual approach to classifying the stem cells beginning from the early morula stage totipotent embryonic stem cells to the unipotent tissue-resident adult stem cells, also called tissue-specific stem cells. (Turk J Hematol 2008; 25: 57-9) Key words: Stem cells, embryonic stem cells, tissue-specific stem cells, classification, progeny. Özet Kök hücresi biyolojisi ve onar›msal t›p görece yeni alanlard›r. Buna karfl›n, son y›llarda çeflitli hastal›klarda tedavi amac›yla kullan›labilme potansiyelleri nedeniyle kök hücrelerine ola¤anüstü bir ilgi art›fl› vard›r. Klasik tan›m›yla kök hücresi, kendini yenileme ad› verilen mekanizmayla farkl›laflmadan kendini ço¤altan veya bir dizi farkl›laflma aflamas›ndan geçerek olgun hücrelere dönüflebilen hücrelerdir. -
Engineering Lineage Potency and Plasticity of Stem Cells Using Epigenetic Molecules Received: 13 December 2017 Anandika Dhaliwal1, Sandra Pelka1, David S
www.nature.com/scientificreports OPEN Engineering Lineage Potency and Plasticity of Stem Cells using Epigenetic Molecules Received: 13 December 2017 Anandika Dhaliwal1, Sandra Pelka1, David S. Gray1 & Prabhas V. Moghe 1,2 Accepted: 11 October 2018 Stem cells are considered as a multipotent regenerative source for diseased and dysfunctional Published: xx xx xxxx tissues. Despite the promise of stem cells, the inherent capacity of stem cells to convert to tissue- specifc 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 diferentiation that human stem cells exhibit based on the source and processing of stem cells. In this study, we screened a library of 84 small molecule pharmacological agents indicated in nucleosomal modifcation and identifed a sub-set of specifc molecules that infuenced osteogenesis in human mesenchymal stem cells (hMSCs) while maintaining cell viability in-vitro. Pre-treatment with fve candidate hits, Gemcitabine, Decitabine, I-CBP112, Chidamide, and SIRT1/2 inhibitor IV, maximally enhanced osteogenesis in-vitro. In contrast, fve distinct molecules, 4-Iodo-SAHA, Scriptaid, AGK2, CI-amidine and Delphidine Chloride maximally inhibited osteogenesis. We then tested the role of these molecules on hMSCs derived from aged human donors and report that small epigenetic molecules, namely Gemcitabine and Chidamide, can signifcantly promote osteogenic diferentiation by 5.9- and 2.3-fold, respectively. Taken together, this study demonstrates new applications of identifed small molecule drugs for sensitively regulating the lineage plasticity fates of bone-marrow derived mesenchymal stem cells through modulating the epigenetic profle of the cells. -
REX1 Promotes EMT-Induced Cell Metastasis by Activating the JAK2/ STAT3-Signaling Pathway by Targeting SOCS1 in Cervical Cancer
Oncogene (2019) 38:6940–6957 https://doi.org/10.1038/s41388-019-0906-3 ARTICLE REX1 promotes EMT-induced cell metastasis by activating the JAK2/ STAT3-signaling pathway by targeting SOCS1 in cervical cancer 1 2 1 1,2 Yu-Ting Zeng ● Xiao-Fang Liu ● Wen-Ting Yang ● Peng-Sheng Zheng Received: 15 November 2018 / Revised: 3 July 2019 / Accepted: 5 July 2019 / Published online: 13 August 2019 © The Author(s) 2019. This article is published with open access Abstract ZFP42 zinc finger protein (REX1), a pluripotency marker in mouse pluripotent stem cells, has been identified as a tumor suppressor in several human cancers. However, the function of REX1 in cervical cancer remains unknown. Both IHC and western blot assays demonstrated that the expression of REX1 protein in cervical cancer tissue was much higher than that in normal cervical tissue. A xenograft assay showed that REX1 overexpression in SiHa and HeLa cells facilitated distant metastasis but did not significantly affect tumor formation in vivo. In addition, in vitro cell migration and invasion capabilities were also promoted by REX1. Mechanistically, REX1 overexpression induced epithelial-to-mesenchymal transition (EMT) by upregulating VIMENTIN and downregulating E-CADHERIN. Furthermore, the JAK2/STAT3- 1234567890();,: 1234567890();,: signaling pathway was activated in REX1-overexpressing cells, which also exhibited increased levels of p-STAT3 and p- JAK2, as well as downregulated expression of SOCS1, which is an inhibitor of the JAK2/STAT3-signaling pathway, at both the transcriptional and translational levels. A dual-luciferase reporter assay and qChIP assays confirmed that REX1 trans- suppressed the expression of SOCS1 by binding to two specific regions of the SOCS1 promoter. -
Ethical Challenges in Organoid Use
Article Ethical Challenges in Organoid Use Vasiliki Mollaki Hellenic National Bioethics Commission, PC 10674 Athens, Greece; [email protected] Abstract: Organoids hold great promises for numerous applications in biomedicine and biotech- nology. Despite its potential in science, organoid technology poses complex ethical challenges that may hinder any future benefits for patients and society. This study aims to analyze the multifaceted ethical issues raised by organoids and recommend measures that must be taken at various levels to ensure the ethical use and application of this technology. Organoid technology raises several serious ethics issues related to the source of stem cells for organoid creation, informed consent and privacy of cell donors, the moral and legal status of organoids, the potential acquisition of human “characteristics or qualities”, use of gene editing, creation of chimeras, organoid transplantation, commercialization and patentability, issues of equity in the resulting treatments, potential misuse and dual use issues and long-term storage in biobanks. Existing guidelines and regulatory frameworks that are applicable to organoids are also discussed. It is concluded that despite the serious ethical challenges posed by organoid use and biobanking, we have a moral obligation to support organoid research and ensure that we do not lose any of the potential benefits that organoids offer. In this direction, a four-step approach is recommended, which includes existing regulations and guidelines, special regulatory provisions that may be needed, public engagement and continuous monitoring of the rapid advancements in the field. This approach may help maximize the biomedical and social benefits of organoid technology and contribute to future governance models in organoid technology. -
Effect of Long-Term 3D Spheroid Culture on WJ-MSC
cells Article Effect of Long-Term 3D Spheroid Culture on WJ-MSC Agnieszka Kaminska 1, Aleksandra Wedzinska 1 , Marta Kot 2 and Anna Sarnowska 1,2,* 1 Mossakowski Medical Research Centre, Translational Platform for Regenerative Medicine, Polish Academy of Science, 02-106 Warsaw, Poland; [email protected] (A.K.); [email protected] (A.W.) 2 Mossakowski Medical Research Centre, Department of Stem Cell Bioengineering, Polish Academy of Sciences, 02-106 Warsaw, Poland; [email protected] * Correspondence: [email protected]; Tel.: +48-22-6086598 Abstract: The aim of our work was to develop a protocol enabling a derivation of mesenchymal stem/stromal cell (MSC) subpopulation with increased expression of pluripotent and neural genes. For this purpose we used a 3D spheroid culture system optimal for neural stem cells propagation. Although 2D culture conditions are typical and characteristic for MSC, under special treatment these cells can be cultured for a short time in 3D conditions. We examined the effects of prolonged 3D spheroid culture on MSC in hope to select cells with primitive features. Wharton Jelly derived MSC (WJ-MSC) were cultured in 3D neurosphere induction medium for about 20 days in vitro. Then, cells were transported to 2D conditions and confront to the initial population and population constantly cultured in 2D. 3D spheroids culture of WJ-MSC resulted in increased senescence, de- creased stemness and proliferation. However long-termed 3D spheroid culture allowed for selection of cells exhibiting increased expression of early neural and SSEA4 markers what might indicate the survival of cell subpopulation with unique features. -
Stem Cell Therapy and Gene Transfer for Regeneration
Gene Therapy (2000) 7, 451–457 2000 Macmillan Publishers Ltd All rights reserved 0969-7128/00 $15.00 www.nature.com/gt MILLENNIUM REVIEW Stem cell therapy and gene transfer for regeneration T Asahara, C Kalka and JM Isner Cardiovascular Research and Medicine, St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, MA, USA The committed stem and progenitor cells have been recently In this review, we discuss the promising gene therapy appli- isolated from various adult tissues, including hematopoietic cation of adult stem and progenitor cells in terms of mod- stem cell, neural stem cell, mesenchymal stem cell and ifying stem cell potency, altering organ property, accelerating endothelial progenitor cell. These adult stem cells have sev- regeneration and forming expressional organization. Gene eral advantages as compared with embryonic stem cells as Therapy (2000) 7, 451–457. their practical therapeutic application for tissue regeneration. Keywords: stem cell; gene therapy; regeneration; progenitor cell; differentiation Introduction poietic stem cells to blood cells. The determined stem cells differentiate into ‘committed progenitor cells’, which The availability of embryonic stem (ES) cell lines in mam- retain a limited capacity to replicate and phenotypic fate. malian species has greatly advanced the field of biologi- In the past decade, researchers have defined such com- cal research by enhancing our ability to manipulate the mitted stem or progenitor cells from various tissues, genome and by providing model systems to examine including bone marrow, peripheral blood, brain, liver cellular differentiation. ES cells, which are derived from and reproductive organs, in both adult animals and the inner mass of blastocysts or primordial germ cells, humans (Figure 1). -
Electrophysiology Read-Out Tools for Brain-On-Chip Biotechnology
micromachines Review Electrophysiology Read-Out Tools for Brain-on-Chip Biotechnology Csaba Forro 1,2,†, Davide Caron 3,† , Gian Nicola Angotzi 4,†, Vincenzo Gallo 3, Luca Berdondini 4 , Francesca Santoro 1 , Gemma Palazzolo 3,* and Gabriella Panuccio 3,* 1 Tissue Electronics, Fondazione Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci, 53-80125 Naples, Italy; [email protected] (C.F.); [email protected] (F.S.) 2 Department of Chemistry, Stanford University, Stanford, CA 94305, USA 3 Enhanced Regenerative Medicine, Fondazione Istituto Italiano di Tecnologia, Via Morego, 30-16163 Genova, Italy; [email protected] (D.C.); [email protected] (V.G.) 4 Microtechnology for Neuroelectronics, Fondazione Istituto Italiano di Tecnologia, Via Morego, 30-16163 Genova, Italy; [email protected] (G.N.A.); [email protected] (L.B.) * Correspondence: [email protected] (G.P.); [email protected] (G.P.); Tel.: +39-010-2896-884 (G.P.); +39-010-2896-493 (G.P.) † These authors contributed equally to this paper. Abstract: Brain-on-Chip (BoC) biotechnology is emerging as a promising tool for biomedical and pharmaceutical research applied to the neurosciences. At the convergence between lab-on-chip and cell biology, BoC couples in vitro three-dimensional brain-like systems to an engineered microfluidics platform designed to provide an in vivo-like extrinsic microenvironment with the aim of replicating tissue- or organ-level physiological functions. BoC therefore offers the advantage of an in vitro repro- duction of brain structures that is more faithful to the native correlate than what is obtained with conventional cell culture techniques. -
Measurement of Hematopoietic Stem Cell Potency Prior to Transplantation
WHITE PAPER Measurement of Hematopoietic Stem Cell Potency Prior to Transplantation February, 2009 This White Paper is a forward-looking statement. It represents the present state of the art and future technology in the field of stem cell potency testing. The views expressed in this White Paper are those of HemoGenix®, Inc. Changing the Paradigm Introduction The increased number of potential cellular therapies over recent years has necessitated stricter regulations to improve efficacy of the treatment and reduce risk to the patient. One of the regulations that was implemented by the European Medicines Agency (EMEA), Committee for Medicinal Products for Human Use (CHMP) on 15 May 2008 and the publication of a Draft Guidance by the United States Food and Drug Administration (FDA) in October 2008, was the requirement to measure the potency of a cellular product prior to administration to the patient. There have been two primary difficulties with these regulations. One of the difficulties encountered by the cellular therapy field is the understanding of what potency of a cellular product means. In the United States (U.S.), potency is actually defined in the Code of Federal Regulations (CFR) in Section 21, 600.3 “to mean the specific ability or capacity of the product, as indicated by appropriate laboratory tests or by adequately controlled clinical data obtained through the administration of the product in the manner intended, to effect a given result”. In the implemented EMEA “Guideline on potency testing of cell based immunotherapy medicinal products for the treatment of cancer”, potency is simply indicated as a “quantitative measure of biological activity” of the cell based immunotherapy product.