Search results for "pluripotent"
showing 10 items of 96 documents
Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery
2020
Spinocerebellar ataxia type-1 (SCA1) is caused by an abnormally expanded polyglutamine (polyQ) tract in ataxin-1. These expansions are responsible for protein misfolding and self-assembly into intranuclear inclusion bodies (IIBs) that are somehow linked to neuronal death. However, owing to lack of a suitable cellular model, the downstream consequences of IIB formation are yet to be resolved. Here, we describe a nuclear protein aggregation model of pathogenic human ataxin-1 and characterize IIB effects. Using an inducible Sleeping Beauty transposon system, we overexpressed the ATXN1(Q82) gene in human mesenchymal stem cells that are resistant to the early cytotoxic effects caused by the expr…
Immunomodulatory effects of stem cells: Therapeutic option for neurodegenerative disorders.
2017
Stem cells have the capability of self-renewal and can differentiate into different cell types that might be used in regenerative medicine. Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) currently lack effective treatments. Although stem cell therapy is still on the way from bench to bedside, we consider that it might provide new hope for patients suffering with neurodegenerative diseases. In this article, we will give an overview of recent studies on the potential therapeutic use of mesenchymal stem cells (MSCs), neural stem cells (NSCs), embryonic stem cells (ESCs), induced pluripotent…
Use of Stem Cell Extracellular Vesicles as a “Holistic” Approach to CNS Repair
2020
Neurodegeneration is a hallmark of many diseases and disorders of the central nervous system (CNS). High levels of neuroinflammation are often associated with irreparable damage to CNS cells due to the dysregulation of signaling cascades that are unable to restore a homeostatic balance. Due to the inherent complexity of the CNS, development of CNS-related therapeutics has met limited success. While stem cell therapy has been evaluated in the context of CNS repair, the mechanisms responsible for their functional properties have not been clearly defined. In recent years, there has been growing interest in the use of stem cell extracellular vesicles (EVs) for the treatment of various CNS patho…
Mitochondrial Dynamics: In Cell Reprogramming as It Is in Cancer
2017
Somatic cells can be reprogrammed into a pluripotent cellular state similar to that of embryonic stem cells. Given the significant physiological differences between the somatic and pluripotent cells, cell reprogramming is associated with a profound reorganization of the somatic phenotype at all levels. The remodeling of mitochondrial morphology is one of these dramatic changes that somatic cells have to undertake during cell reprogramming. Somatic cells transform their tubular and interconnected mitochondrial network to the fragmented and isolated organelles found in pluripotent stem cells early during cell reprogramming. Accordingly, mitochondrial fission, the process whereby the mitochond…
Evaluating Cell Identity from Transcription Profiles
2018
SummaryInduced pluripotent stem cells (iPS) and direct lineage programming offer promising autologous and patient-specific sources of cells for personalized drug-testing and cell-based therapy. Before these engineered cells can be widely used, it is important to evaluate how well the engineered cell types resemble their intended target cell types. We have developed a method to generate CellScore, a cell identity score that can be used to evaluate the success of an engineered cell type in relation to both its initial and desired target cell type, which are used as references. Of 20 cell transitions tested, the most successful transitions were the iPS cells (CellScore > 0.9), while other t…
Human Pluripotent Stem Cell-Derived Neuronal Networks:Their Electrical Functionality and Usability for Modelling and Toxicology
2011
Micro electrode array (MEA)-based platforms have been used to study neuronal networks for decades. The used cells have, for the most part, been rodent primary neurons. The gained knowledge has indeed increased the understanding of neuronal network development and maturation both in vitro and in vivo. If aiming to understand the development of human brain, however, the used cell type should preferably be of human origin due to difficult interpolation from the rodent cell data. In addition, the development of functional human neuronal networks would open up a new era for, e.g., toxicology testing, drug screening and disease modelling. The use of MEA with bioelectrically active cells was first…
Human POMC processing in vitro and in vivo revealed by quantitative peptidomics
2018
ABSTRACTHuman obesity can result from the aberrant production or processing of proopiomelanocortin (POMC) in hypothalamic neurons, but it is unclear which human POMC-derived peptides are most relevant to body weight regulation. To address this question, we analysed both hypothalamic neurons derived from human pluripotent stem cells (hPSCs) and primary human hypothalamic tissue using quantitative liquid chromatography tandem mass spectroscopy (LC-MS/MS). In both in vitro- and in vivo-derived samples, we found that POMC was processed into β-melanocyte stimulating hormone (β-MSH), whose existence in the human brain has been controversial. β-MSH and desacetyl α-MSH (d-α-MSH) were produced at ro…
Modulação gênica em embriões humanos
2018
O recente implemento de moderna tecnologia -CRISPR/Cas9- possibilitou o avanço inquestionável da edição gênica em linhagem germinativa humana, seja por meio da manipulação de células precursoras de gametas, células tronco pluripotentes, gametas ou, até mesmo, de embriões. Mesmo levando em conta os benefícios terapêuticos preventivos demonstrados nas pesquisas básicas e préclínicas em embriões humanos, tais investigações encontram barreiras de aceitação em todo o mundo. Tal situação exige mudança de atitude no sentido de incrementar o debate em torno da aplicabilidade dessas novas tecnologias. Assim, a adequação das atuais regulamentações faz-se necessária e deve incluir a superação dos desa…
Identification and expansion of human osteosarcoma-cancer-stem cells by long-term 3-aminobenzamide treatment
2009
A novel cancer stem-like cell line (3AB-OS), expressing a number of pluripotent stem cell markers, was irreversibly selected from human osteosarcoma MG-63 cells by long-term treatment (100 days) with 3-aminobenzamide (3AB). 3AB-OS cells are a heterogeneous and stable cell population composed by three types of fibroblastoid cells, spindle-shaped, polygonal-shaped, and rounded-shaped. With respect to MG-63 cells, 3AB-OS cells are extremely smaller, possess a much greater capacity to form spheres, a stronger self-renewal ability and much higher levels of cell cycle markers which account for G1-S/G2-M phases progression. Differently from MG-63 cells, 3AB-OS cells can be reseeded unlimitedly wit…
The Disease-Specific Phenotype in Cardiomyocytes Derived from Induced Pluripotent Stem Cells of Two Long QT Syndrome Type 3 Patients
2013
Long QT syndromes (LQTS) are heritable diseases characterized by prolongation of the QT interval on an electrocardiogram, which often leads to syncope and sudden cardiac death. Here we report the generation of induced pluripotent stems (iPS) cells from two patients with LQTS type 3 carrying a different point mutation in a sodium channel Nav1.5 (p.V240M and p.R535Q) and functional characterization of cardiomyocytes (CM) derived from them. The iPS cells exhibited all characteristic properties of pluripotent stem cells, maintained the disease-specific mutation and readily differentiated to CM. The duration of action potentials at 50% and 90% repolarization was longer in LQTS-3 CM as compared t…