scholarly journals Modeling Cardiomyopathies in a Dish: State-of-the-Art and Novel Perspectives on hiPSC-Derived Cardiomyocytes Maturation

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 730
Author(s):  
Francesco Lodola ◽  
Verónica Celeste De Giusti ◽  
Claudia Maniezzi ◽  
Daniele Martone ◽  
Ilaria Stadiotti ◽  
...  
Keyword(s):  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
State Of The Art ◽  
Heart Tissue ◽  
Primary Cells ◽  
Stem Cell Technology ◽  
Cells Of Origin ◽  
Human Ipscs ◽  
Induced Pluripotent

The stem cell technology and the induced pluripotent stem cells (iPSCs) production represent an excellent alternative tool to study cardiomyopathies, which overcome the limitations associated with primary cardiomyocytes (CMs) access and manipulation. CMs from human iPSCs (hiPSC–CMs) are genetically identical to patient primary cells of origin, with the main electrophysiological and mechanical features of CMs. The key issue to be solved is to achieve a degree of structural and functional maturity typical of adult CMs. In this perspective, we will focus on the main differences between fetal-like hiPSC-CMs and adult CMs. A viewpoint is given on the different approaches used to improve hiPSC-CMs maturity, spanning from long-term culture to complex engineered heart tissue. Further, we outline limitations and future developments needed in cardiomyopathy disease modeling.

Human Stem Cell–Derived Models: Lessons for Autoimmune Diseases of the Nervous System

2018 ◽  
Vol 25 (3) ◽  
pp. 199-207 ◽  
Author(s):  
Oliver Harschnitz
Keyword(s):  
Nervous System ◽  
Stem Cell ◽  
Disease Modeling ◽  
Induced Pluripotent Stem Cell ◽  
Human Stem Cell ◽  
Stem Cell Technology ◽  
Neuronal Autoantibodies ◽  
Induced Pluripotent ◽  
Underlying Pathogenesis

Autoimmunity of the peripheral and central nervous system is an important cause of disease and long-term neurological disability. Autoantibodies can target both intracellular and extracellular neuronal epitopes. Autoantibodies that target cell-surface epitopes infer pathogenicity through several distinct mechanisms, while patients often respond to immunotherapy. However, the underlying pathogenesis of these autoantibodies is yet to be fully understood. Human stem cell–based disease modeling, and the rise of induced pluripotent stem cell technology in particular, has revolutionized the fields of disease modeling and therapeutic screening for neurological disorders. These human disease models offer a unique platform in which to study autoimmunity of the nervous system. Here, we take an in-depth look at the possibilities that these models provide to study neuronal autoantibodies and their underlying pathogenesis.

scholarly journals The application of patient-derived induced pluripotent stem cells for modeling and treatment of Alzheimer’s disease

2019 ◽  
Vol 5 (1) ◽  
pp. 21-40 ◽  
Author(s):  
Fabin Han ◽  
Chuanguo Liu ◽  
Jin Huang ◽  
Juanli Chen ◽  
Chuanfei Wei ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Human Brain ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Autologous Transplantation ◽  
Human Ipscs ◽  
Induced Pluripotent

Alzheimer’s disease (AD) is the most prevalent age-related neurodegenerative disease which is mainly caused by aggregated protein plaques in degenerating neurons of the brain. These aggregated protein plaques are mainly consisting of amyloid β (Aβ) fibrils and neurofibrillary tangles (NFTs) of phosphorylated tau protein. Even though the transgenic murine models can recapitulate some of the AD phenotypes, they are not the human cell models of AD. Recent breakthrough in somatic cell reprogramming made it available to use induced pluripotent stem cells (iPSCs) for patientspecific disease modeling and autologous transplantation therapy. Human iPSCs provide alternative ways to obtain specific human brain cells of AD patients to study the molecular mechanisms and therapeutic approaches for familial and sporadic forms of AD. After differentiation into neuronal cells, iPSCs have enabled the investigation of the complex aetiology and timescale over which AD develops in human brain. Here, we first go over the pathological process of and transgenic models of AD. Then we discuss the application of iPSC for disease model and cell transplantation. At last the challenges and future applications of iPSCs for AD will be summarized to propose cell-based approaches for the treatment of this devastating disorder.

scholarly journals Human iPSC banking: barriers and opportunities

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Ching-Ying Huang ◽  
Chun-Lin Liu ◽  
Chien-Yu Ting ◽  
Yueh-Ting Chiu ◽  
Yu-Che Cheng ◽  
...  
Keyword(s):  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Toxicity Assessment ◽  
Cell Therapies ◽  
The Past ◽  
Human Ipscs ◽  
Ongoing Development ◽  
Barriers And Opportunities ◽  
Induced Pluripotent ◽  
Human Ipsc

Abstract The introduction of induced pluripotent stem cells (iPSCs) has opened up the potential for personalized cell therapies and ushered in new opportunities for regenerative medicine, disease modeling, iPSC-based drug discovery and toxicity assessment. Over the past 10 years, several initiatives have been established that aim to collect and generate a large amount of human iPSCs for scientific research purposes. In this review, we compare the construction and operation strategy of some iPSC banks as well as their ongoing development. We also introduce the technical challenges and offer future perspectives pertaining to the establishment and management of iPSC banks.

scholarly journals Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells

2016 ◽  
Vol 17 (2) ◽  
pp. 256 ◽  
Author(s):  
Mohammed Kawser Hossain ◽  
Ahmed Abdal Dayem ◽  
Jihae Han ◽  
Subbroto Kumar Saha ◽  
Gwang-Mo Yang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cells ◽  
Drug Discovery ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Recent Advances ◽  
Induced Pluripotent

scholarly journals Utilising Induced Pluripotent Stem Cells in Neurodegenerative Disease Research: Focus on Glia

2021 ◽  
Vol 22 (9) ◽  
pp. 4334
Author(s):  
Katrina Albert ◽  
Jonna Niskanen ◽  
Sara Kälvälä ◽  
Šárka Lehtonen
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Induced Pluripotent Stem Cells ◽  
Glial Cells ◽  
Pluripotent Stem Cells ◽  
Cell Types ◽  
Human Ipscs ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPSCs) are a self-renewable pool of cells derived from an organism’s somatic cells. These can then be programmed to other cell types, including neurons. Use of iPSCs in research has been two-fold as they have been used for human disease modelling as well as for the possibility to generate new therapies. Particularly in complex human diseases, such as neurodegenerative diseases, iPSCs can give advantages over traditional animal models in that they more accurately represent the human genome. Additionally, patient-derived cells can be modified using gene editing technology and further transplanted to the brain. Glial cells have recently become important avenues of research in the field of neurodegenerative diseases, for example, in Alzheimer’s disease and Parkinson’s disease. This review focuses on using glial cells (astrocytes, microglia, and oligodendrocytes) derived from human iPSCs in order to give a better understanding of how these cells contribute to neurodegenerative disease pathology. Using glia iPSCs in in vitro cell culture, cerebral organoids, and intracranial transplantation may give us future insight into both more accurate models and disease-modifying therapies.

scholarly journals A non-invasive method to generate induced pluripotent stem cells from primate urine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Johanna Geuder ◽  
Lucas E. Wange ◽  
Aleksandar Janjic ◽  
Jessica Radmer ◽  
Philipp Janssen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Sendai Virus ◽  
Cell Types ◽  
Urine Samples ◽  
Comparative Approach ◽  
Non Invasive ◽  
Human Ipscs ◽  
Induced Pluripotent

AbstractComparing the molecular and cellular properties among primates is crucial to better understand human evolution and biology. However, it is difficult or ethically impossible to collect matched tissues from many primates, especially during development. An alternative is to model different cell types and their development using induced pluripotent stem cells (iPSCs). These can be generated from many tissue sources, but non-invasive sampling would decisively broaden the spectrum of non-human primates that can be investigated. Here, we report the generation of primate iPSCs from urine samples. We first validate and optimize the procedure using human urine samples and show that suspension- Sendai Virus transduction of reprogramming factors into urinary cells efficiently generates integration-free iPSCs, which maintain their pluripotency under feeder-free culture conditions. We demonstrate that this method is also applicable to gorilla and orangutan urinary cells isolated from a non-sterile zoo floor. We characterize the urinary cells, iPSCs and derived neural progenitor cells using karyotyping, immunohistochemistry, differentiation assays and RNA-sequencing. We show that the urine-derived human iPSCs are indistinguishable from well characterized PBMC-derived human iPSCs and that the gorilla and orangutan iPSCs are well comparable to the human iPSCs. In summary, this study introduces a novel and efficient approach to non-invasively generate iPSCs from primate urine. This will extend the zoo of species available for a comparative approach to molecular and cellular phenotypes.

scholarly journals Chemically defined and xeno-free culture condition for human extended pluripotent stem cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bei Liu ◽  
Shi Chen ◽  
Yaxing Xu ◽  
Yulin Lyu ◽  
Jinlin Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Culture Condition ◽  
Human Fibroblast ◽  
Culture System ◽  
Disease Modeling ◽  
Directed Differentiation

AbstractExtended pluripotent stem (EPS) cells have shown great applicative potentials in generating synthetic embryos, directed differentiation and disease modeling. However, the lack of a xeno-free culture condition has significantly limited their applications. Here, we report a chemically defined and xeno-free culture system for culturing and deriving human EPS cells in vitro. Xeno-free human EPS cells can be long-term and genetically stably maintained in vitro, as well as preserve their embryonic and extraembryonic developmental potentials. Furthermore, the xeno-free culturing system also permits efficient derivation of human EPS cells from human fibroblast through reprogramming. Our study could have broad utility in future applications of human EPS cells in biomedicine.

scholarly journals Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic Acidemia

2021 ◽  
Vol 22 (3) ◽  
pp. 1161
Author(s):  
Esmeralda Alonso-Barroso ◽  
Belén Pérez ◽  
Lourdes Ruiz Desviat ◽  
Eva Richard
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Ex Vivo ◽  
Disease Model ◽  
Propionic Acidemia ◽  
Heart Tissue ◽  
Altered Expression ◽  
Cellular Models ◽  
Induced Pluripotent

Propionic acidemia (PA), one of the most frequent life-threatening organic acidemias, is caused by mutations in either the PCCA or PCCB genes encoding both subunits of the mitochondrial propionyl-CoA carboxylase (PCC) enzyme. Cardiac alterations (hypertrophy, dilated cardiomyopathy, long QT) are one of the major causes of mortality in patients surviving the neonatal period. To overcome limitations of current cellular models of PA, we generated induced pluripotent stem cells (iPSCs) from a PA patient with defects in the PCCA gene, and successfully differentiated them into cardiomyocytes. PCCA iPSC-derived cardiomyocytes exhibited reduced oxygen consumption, an accumulation of residual bodies and lipid droplets, and increased ribosomal biogenesis. Furthermore, we found increased protein levels of HERP, GRP78, GRP75, SIG-1R and MFN2, suggesting endoplasmic reticulum stress and calcium perturbations in these cells. We also analyzed a series of heart-enriched miRNAs previously found deregulated in the heart tissue of a PA murine model and confirmed their altered expression. Our novel results show that PA iPSC-cardiomyocytes represent a promising model for investigating the pathological mechanisms underlying PA cardiomyopathies, also serving as an ex vivo platform for therapeutic evaluation.

scholarly journals Development of Multilayer Mesenchymal Stem Cell Cell Sheets

2021 ◽  
Vol 1 (1) ◽  
pp. 4-24
Author(s):  
Jun Ochiai ◽  
Yutaka Niihara ◽  
Joan Oliva
Keyword(s):  
Stem Cells ◽  
Stromal Cells ◽  
Pluripotent Stem Cells ◽  
Cell Sheets ◽  
Gene Therapies ◽  
The Past ◽  
Long Term Effect ◽  
Induced Pluripotent ◽  
New Guidelines

Cell and gene therapies have been developing dramatically over the past decade. To face and adapt to the development of these new therapies, the Food and Drug Administration (FDA) wrote and updated new guidelines from 2016 and keep updating them. Mesenchymal stem cells (MSCs) are the most used cells for treatment, far ahead from the induced pluripotent stem cells (iPSCs), based on registered clinical trials at clinicaltrials.gov. They are widely used because of their differentiation capacity and their anti-inflammatory properties, but some controversies still require clear answers. Additional studies are needed to determine the dosage, the number, and the route of injections (location and transplantation method), and if allogenic MSCs are safe compared to autologous MSC injection, including their long-term effect. In this review, we summarize the research our company is conducting with the adipose stromal cells in engineering cell sheets and their potential application.

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