scholarly journals Adenoviral Vectors Meet Gene Editing: A Rising Partnership for the Genomic Engineering of Human Stem Cells and Their Progeny

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 953 ◽  
Author(s):  
Francesca Tasca ◽  
Qian Wang ◽  
Manuel A.F.V. Gonçalves
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Dna Sequences ◽  
Adenoviral Vector ◽  
Gene Editing ◽  
Adenoviral Vectors ◽  
Human Cells ◽  
Human Stem Cells ◽  
Cell Technologies ◽  
The Impact

Gene editing permits changing specific DNA sequences within the vast genomes of human cells. Stem cells are particularly attractive targets for gene editing interventions as their self-renewal and differentiation capabilities consent studying cellular differentiation processes, screening small-molecule drugs, modeling human disorders, and testing regenerative medicines. To integrate gene editing and stem cell technologies, there is a critical need for achieving efficient delivery of the necessary molecular tools in the form of programmable DNA-targeting enzymes and/or exogenous nucleic acid templates. Moreover, the impact that the delivery agents themselves have on the performance and precision of gene editing procedures is yet another critical parameter to consider. Viral vectors consisting of recombinant replication-defective viruses are under intense investigation for bringing about efficient gene-editing tool delivery and precise gene-editing in human cells. In this review, we focus on the growing role that adenoviral vectors are playing in the targeted genetic manipulation of human stem cells, progenitor cells, and their differentiated progenies in the context of in vitro and ex vivo protocols. As preamble, we provide an overview on the main gene editing principles and adenoviral vector platforms and end by discussing the possibilities ahead resulting from leveraging adenoviral vector, gene editing, and stem cell technologies.

Concise Review; Effects of Antibiotics and Antimycotics on the Biological Properties of Human Pluripotent and Multipotent Stem Cells

2020 ◽  
Vol 16 ◽  
Author(s):  
Maryam Farzaneh
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Culture Media ◽  
Embryonic Stem ◽  
Great Promise ◽  
Human Stem Cells ◽  
Multipotent Stem Cells ◽  
The Impact

Abstract:: Human pluripotent stem cells (PSCs) including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the remarkable potential to self-renew and develop into various cell lineages. Human mesenchymal stem cells (MSCs) or multipotent stem cells that are present in various organs can self-renew and differentiate into multiple mesenchymal lineages. Both human PSCs and MSCs hold great promise in cell-based therapies, disease modeling, drug discovery, and regenerative medicine. Human stem cells must be cultured under the optimal conditions to use them in transplantology. Therefore, researchers must ensure the sterility of human stem cell lines. Bacterial contamination is a common problem in laboratories and major precautions are required to detect the types of microorganisms, eliminate, and prevent contamination in cell cultures. Stem cell culture media usually contains antibiotics and antimycotics such as penicillin-streptomycin (pen-strep), gentamicin, and amphotericin B (AmB) to avoid bacterial, fungal, and yeast contaminants. Numerous publications recognized the serious effect of antibiotics and antimycotics on in vitro properties of human stem cells, including proliferation, differentiation, survival, and genetic instability. This review study aimed to understand the impact of routinely used antibiotics and antimycotics such as pen-strep, gentamicin, and AmB on viability, proliferation, and functional properties (differentiation and pluripotency) of human PSCs and MSCs.

scholarly journals Reprogramming of human cells to pluripotency induces CENP-A chromatin depletion

Open Biology ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 200227
Author(s):  
Inês Milagre ◽  
Carolina Pereira ◽  
Raquel A. Oliveira ◽  
Lars E. T. Jansen
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Physiological Role ◽  
Cell Types ◽  
Human Cells ◽  
Early Event ◽  
Human Stem Cells ◽  
Centromere Function ◽  
Underlying Causes

Pluripotent stem cells (PSCs) are central to development as they are the precursors of all cell types in the embryo. Therefore, maintaining a stable karyotype is essential, both for their physiological role as well as for their use in regenerative medicine. Karyotype abnormalities in PSCs in culture are common but the underlying causes remain unknown. To gain insight, we explore the composition of the centromere and kinetochore in human embryonic and induced PSCs. Centromere function depends on CENP-A nucleosome-defined chromatin. We show that while PSCs maintain abundant pools of CENP-A, CENP-C and CENP-T, these essential centromere components are strongly reduced at stem cell centromeres. Outer kinetochore recruitment is also impaired to a lesser extent, indicating an overall weaker kinetochore while the inner centromere protein Aurora B remains unaffected. We further show that, similar to differentiated human cells, CENP-A chromatin assembly in PSCs requires transition into G1 phase. Finally, reprogramming experiments indicate that reduction of centromeric CENP-A levels is an early event during dedifferentiation, coinciding with global chromatin remodelling. Our characterization of centromeres in human stem cells suggests a possible link between impaired centromere function and stem cell aneuploidies.

scholarly journals Reprogramming of Human Cells to Pluripotency Induces CENP-A Chromatin Depletion

2020 ◽  
Author(s):  
Inês Milagre ◽  
Carolina Pereira ◽  
Raquel Oliveira ◽  
Lars E.T. Jansen
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Physiological Role ◽  
Cell Types ◽  
Human Cells ◽  
Early Event ◽  
Human Stem Cells ◽  
Centromere Function

SummaryPluripotent stem cells (PSCs) are central to development as they are the precursors of all cell types in the embryo. Therefore, maintaining a stable karyotype is essential, both for their physiological role as well as for use in regenerative medicine. In culture, an estimated 10-30% of PSC lines present karyotypic abnormalities, but the underlying causes remain unknown. To gain insight into the mitotic capacity of human embryonic stem cells and induced pluripotent stem cells, we explore the structure of the centromere and kinetochore. Centromere function depends on CENP-A nucleosome-defined chromatin. We show that while PSCs maintain abundant pools of CENP-A, CENP-C and CENP-T, these essential centromere components are strongly reduced at stem cell centromeres. Outer kinetochore recruitment is also impaired to a lesser extent, indicating an overall weaker kinetochore. This impairment is specific for the kinetochore forming centromere complex while the inner centromere protein Aurora B remains unaffected. We further show that, similar to differentiated human cells, CENP-A chromatin assembly in PSCs requires transition into G1 phase. Finally, reprogramming experiments indicate that reduction of centromeric CENP-A levels is an early event during dedifferentiation, coinciding with global chromatin remodelling. Our characterisation of centromeres in human stem cells drives new hypotheses including a possible link between impaired centromere function and stem cell aneuploidies.

scholarly journals Telomere length set point regulation in human pluripotent stem cells critically depends on the shelterin protein TPP1

2020 ◽  
Vol 31 (23) ◽  
pp. 2583-2596
Author(s):  
John M. Boyle ◽  
Kelsey M. Hennick ◽  
Samuel G. Regalado ◽  
Jacob M. Vogan ◽  
Xiaozhu Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Telomere Length ◽  
Pluripotent Stem Cells ◽  
Human Stem Cells ◽  
Set Point ◽  
Hypomorphic Allele ◽  
Point Control ◽  
Set Point Control ◽  
Stem Cell Lines

To better understand telomere length set point control in human stem cells, we generated knockout stem cell lines for TPP1 and contrasted their phenotypes with those of homozygous TPP1 L104A mutant stem cells. This comparison reveals that TPP1 L104A is not a hypomorphic allele but formally establishes TPP1 L104 as a dissociation of function mutant.

Research and Findings

2009 ◽  
Vol 13 (04) ◽  
pp. 76-79
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Disease Management ◽  
Cancer Risk ◽  
Cancer Patients ◽  
Drug Dosage ◽  
Human Stem Cells ◽  
New Materials ◽  
East Asians ◽  
Lower Drug

Australian Scientists Reach Breakthrough in Stem Cell Research. Breakthrough in Disease Management of Chikungunya Fever by Singapore Researchers. MicroRNAs Lead to Formation or Suppression of Tumors? Singapore and US Scientists Share Results. Singapore and South Korea to Invent More New Materials. Asian Blood Cancer Patients Respond Better with a Lower Drug Dosage. Safer Ethical Way to Make Human Stem Cells. "Blushing" Response from Alcohol Drinking Signals Increased Cancer Risk Among East Asians.

scholarly journals Effects of Co-Culture of Graphene Oxide Scaffolds with Different Concentrations and Umbilical Mesenchymal Stem Cells on the Proliferation and Differentiation of Stem Cells

2021 ◽  
Author(s):  
Aifeng Liu ◽  
Jixin Chen ◽  
Shuwei Gong ◽  
Qiang Wei ◽  
Ye Yuan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Graphene Oxide ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Umbilical Cord ◽  
High Porosity ◽  
Proliferation And Differentiation ◽  
Scaffold Materials ◽  
The Impact

Abstract The main role of the scaffold materials is to enable cells to survive in the scaffold binding as while as to further promote their proliferation and differentiation ability. For mesenchymal stem cell, the scaffold could provide an environment for them to maintain their phenotype, and synthesize all necessary molecules and proteins. Generally, scaffold materials for stem cell need to possess basic characteristics such as high porosity, large surface area, surface rigidity and biodegradability. Thus, the two-dimensional graphene oxide (GO) with oxygen-containing functional groups may be suitable scaffold materials for mesenchymal stem cell culture.MethodsIn this study, the effect of GO on the value-added differentiation activity of mesenchymal stem cell was systematically investigated. ResultsIt was found that low concentration of GO and sufficient concentration of umbilical cord mesenchymal stem cells are suitable for the second Co-culture. Furthermore, the addition of hyaluronic acid will make this culture more evenly distributed. ConclusionsThe adsorption of GO on umbilical cord mesenchymal stem cells can also make the two closely linked, which avoids the impact of animal joint activities on cells.

scholarly journals The impact of transposable element activity on therapeutically relevant human stem cells

Mobile DNA ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Gerald G. Schumann ◽  
Nina V. Fuchs ◽  
Pablo Tristán-Ramos ◽  
Attila Sebe ◽  
Zoltán Ivics ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transposable Element ◽  
Human Stem Cells ◽  
Element Activity ◽  
The Impact

scholarly journals The Role of Tryptophan Metabolites in Musculoskeletal Stem Cell Aging

2020 ◽  
Vol 21 (18) ◽  
pp. 6670
Author(s):  
Jordan Marcano Anaya ◽  
Wendy B. Bollag ◽  
Mark W. Hamrick ◽  
Carlos M. Isales
Keyword(s):  
Bone Mineral Density ◽  
Stem Cells ◽  
Stem Cell ◽  
Fracture Risk ◽  
Bone Mineral ◽  
Stem Cell Differentiation ◽  
Tryptophan Metabolism ◽  
Mineral Density ◽  
Tryptophan Metabolites ◽  
The Impact

Although aging is considered a normal process, there are cellular and molecular changes that occur with aging that may be detrimental to health. Osteoporosis is one of the most common age-related degenerative diseases, and its progression correlates with aging and decreased capacity for stem cell differentiation and proliferation in both men and women. Tryptophan metabolism through the kynurenine pathway appears to be a key factor in promoting bone-aging phenotypes, promoting bone breakdown and interfering with stem cell function and osteogenesis; however, little data is available on the impact of tryptophan metabolites downstream of kynurenine. Here we review available data on the impact of these tryptophan breakdown products on the body in general and, when available, the existing evidence of their impact on bone. A number of tryptophan metabolites (e.g., 3-hydroxykynurenine (3HKYN), kynurenic acid (KYNA) and anthranilic acid (AA)) have a detrimental effect on bone, decreasing bone mineral density (BMD) and increasing fracture risk. Other metabolites (e.g., 3-hydroxyAA, xanthurenic acid (XA), picolinic acid (PIA), quinolinic acid (QA), and NAD+) promote an increase in bone mineral density and are associated with lower fracture risk. Furthermore, the effects of other tryptophan breakdown products (e.g., serotonin) are complex, with either anabolic or catabolic actions on bone depending on their source. The mechanisms involved in the cellular actions of these tryptophan metabolites on bone are not yet fully known and will require further research as they are potential therapeutic targets. The current review is meant as a brief overview of existing English language literature on tryptophan and its metabolites and their effects on stem cells and musculoskeletal systems. The search terms used for a Medline database search were: kynurenine, mesenchymal stem cells, bone loss, tryptophan metabolism, aging, and oxidative stress.

scholarly journals Isolation and Culture of Human Stem Cells from Apical Papilla under Low Oxygen Concentration Highlight Original Properties

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1485 ◽  
Author(s):  
Murielle Rémy ◽  
Francesca Ferraro ◽  
Pierre Le Salver ◽  
Sylvie Rey ◽  
Elisabeth Genot ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Oxygen Concentration ◽  
Ambient Air ◽  
Stem Cell Marker ◽  
Autophagic Flux ◽  
Integrin Subunit ◽  
Differentiation Potential ◽  
Apical Papilla ◽  
The Impact

Stem cells isolated from the apical papilla of wisdom teeth (SCAPs) are an attractive model for tissue repair due to their availability, high proliferation rate and potential to differentiate in vitro towards mesodermal and neurogenic lineages. Adult stem cells, such as SCAPs, develop in stem cell niches in which the oxygen concentration [O2] is low (3–8% compared with 21% of ambient air). In this work, we evaluate the impact of low [O2] on the physiology of SCAPs isolated and processed in parallel at 21% or 3% O2 without any hyperoxic shock in ambient air during the experiment performed at 3% O2. We demonstrate that SCAPs display a higher proliferation capacity at 3% O2 than in ambient air with elevated expression levels of two cell surface antigens: the alpha-6 integrin subunit (CD49f) and the embryonic stem cell marker (SSEA4). We show that the mesodermal differentiation potential of SCAPs is conserved at early passage in both [O2], but is partly lost at late passage and low [O2], conditions in which SCAPs proliferate efficiently without any sign of apoptosis. Unexpectedly, we show that autophagic flux is active in SCAPs irrespective of [O2] and that this process remains high in cells even after prolonged exposure to 3% O2.

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