scholarly journals Cell Transdifferentiation and Reprogramming in Disease Modeling: Insights into the Neuronal and Cardiac Disease Models and Current Translational Strategies

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2558
Author(s):  
Rajkumar Singh Kalra ◽  
Jaspreet Kaur Dhanjal ◽  
Mriganko Das ◽  
Birbal Singh ◽  
Rajesh Naithani
Keyword(s):  
Drug Discovery ◽  
Cell Fate ◽  
Cardiac Disease ◽  
Disease Modeling ◽  
Present Report ◽  
Special Focus ◽  
Comprehensive Understanding ◽  
Cell Transdifferentiation ◽  
Translational Strategies ◽  
Original Concept

Cell transdifferentiation and reprogramming approaches in recent times have enabled the manipulation of cell fate by enrolling exogenous/artificial controls. The chemical/small molecule and regulatory components of transcription machinery serve as potential tools to execute cell transdifferentiation and have thereby uncovered new avenues for disease modeling and drug discovery. At the advanced stage, one can believe these methods can pave the way to develop efficient and sensitive gene therapy and regenerative medicine approaches. As we are beginning to learn about the utility of cell transdifferentiation and reprogramming, speculations about its applications in translational therapeutics are being largely anticipated. Although clinicians and researchers are endeavoring to scale these processes, we lack a comprehensive understanding of their mechanism(s), and the promises these offer for targeted and personalized therapeutics are scarce. In the present report, we endeavored to provide a detailed review of the original concept, methods and modalities enrolled in the field of cellular transdifferentiation and reprogramming. A special focus is given to the neuronal and cardiac systems/diseases towards scaling their utility in disease modeling and drug discovery.

scholarly journals Emerging hiPSC Models for Drug Discovery in Neurodegenerative Diseases

2021 ◽  
Vol 22 (15) ◽  
pp. 8196
Author(s):  
Dorit Trudler ◽  
Swagata Ghatak ◽  
Stuart A. Lipton
Keyword(s):  
Drug Discovery ◽  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Disease Modeling ◽  
Induced Pluripotent Stem Cell ◽  
Neural Function ◽  
Neural Cells ◽  
Human Samples ◽  
Healthy Donors ◽  
Induced Pluripotent

Neurodegenerative diseases affect millions of people worldwide and are characterized by the chronic and progressive deterioration of neural function. Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), represent a huge social and economic burden due to increasing prevalence in our aging society, severity of symptoms, and lack of effective disease-modifying therapies. This lack of effective treatments is partly due to a lack of reliable models. Modeling neurodegenerative diseases is difficult because of poor access to human samples (restricted in general to postmortem tissue) and limited knowledge of disease mechanisms in a human context. Animal models play an instrumental role in understanding these diseases but fail to comprehensively represent the full extent of disease due to critical differences between humans and other mammals. The advent of human-induced pluripotent stem cell (hiPSC) technology presents an advantageous system that complements animal models of neurodegenerative diseases. Coupled with advances in gene-editing technologies, hiPSC-derived neural cells from patients and healthy donors now allow disease modeling using human samples that can be used for drug discovery.

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 Human iPSC-Based Modeling of Central Nerve System Disorders for Drug Discovery

2021 ◽  
Vol 22 (3) ◽  
pp. 1203
Author(s):  
Lu Qian ◽  
Julia TCW
Keyword(s):  
Drug Discovery ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Structural Complexity ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Central Nerve System ◽  
Human Ipscs ◽  
Nerve System

A high-throughput drug screen identifies potentially promising therapeutics for clinical trials. However, limitations that persist in current disease modeling with limited physiological relevancy of human patients skew drug responses, hamper translation of clinical efficacy, and contribute to high clinical attritions. The emergence of induced pluripotent stem cell (iPSC) technology revolutionizes the paradigm of drug discovery. In particular, iPSC-based three-dimensional (3D) tissue engineering that appears as a promising vehicle of in vitro disease modeling provides more sophisticated tissue architectures and micro-environmental cues than a traditional two-dimensional (2D) culture. Here we discuss 3D based organoids/spheroids that construct the advanced modeling with evolved structural complexity, which propels drug discovery by exhibiting more human specific and diverse pathologies that are not perceived in 2D or animal models. We will then focus on various central nerve system (CNS) disease modeling using human iPSCs, leading to uncovering disease pathogenesis that guides the development of therapeutic strategies. Finally, we will address new opportunities of iPSC-assisted drug discovery with multi-disciplinary approaches from bioengineering to Omics technology. Despite technological challenges, iPSC-derived cytoarchitectures through interactions of diverse cell types mimic patients’ CNS and serve as a platform for therapeutic development and personalized precision medicine.

scholarly journals Matrigel Mattress

2015 ◽  
Vol 117 (12) ◽  
pp. 995-1000 ◽  
Author(s):  
Tromondae K. Feaster ◽  
Adrian G. Cadar ◽  
Lili Wang ◽  
Charles H. Williams ◽  
Young Wook Chun ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Single Cell ◽  
Troponin I ◽  
Disease Modeling ◽  
Sodium Current ◽  
Culture Method ◽  
Adult Rabbit ◽  
Standard Equipment ◽  
Cell Contractility ◽  
Contractile Performance

Rationale: The lack of measurable single-cell contractility of human-induced pluripotent stem cell–derived cardiac myocytes (hiPSC-CMs) currently limits the utility of hiPSC-CMs for evaluating contractile performance for both basic research and drug discovery. Objective: To develop a culture method that rapidly generates contracting single hiPSC-CMs and allows quantification of cell shortening with standard equipment used for studying adult CMs. Methods and Results: Single hiPSC-CMs were cultured for 5 to 7 days on a 0.4- to 0.8-mm thick mattress of undiluted Matrigel (mattress hiPSC-CMs) and compared with hiPSC-CMs maintained on a control substrate (<0.1-mm thick 1:60 diluted Matrigel, control hiPSC-CMs). Compared with control hiPSC-CMs, mattress hiPSC-CMs had more rod-shape morphology and significantly increased sarcomere length. Contractile parameters of mattress hiPSC-CMs measured with video-based edge detection were comparable with those of freshly isolated adult rabbit ventricular CMs. Morphological and contractile properties of mattress hiPSC-CMs were consistent across cryopreserved hiPSC-CMs generated independently at another institution. Unlike control hiPSC-CMs, mattress hiPSC-CMs display robust contractile responses to positive inotropic agents, such as myofilament calcium sensitizers. Mattress hiPSC-CMs exhibit molecular changes that include increased expression of the maturation marker cardiac troponin I and significantly increased action potential upstroke velocity because of a 2-fold increase in sodium current ( I Na ). Conclusions: The Matrigel mattress method enables the rapid generation of robustly contracting hiPSC-CMs and enhances maturation. This new method allows quantification of contractile performance at the single-cell level, which should be valuable to disease modeling, drug discovery, and preclinical cardiotoxicity testing.

The role of stem cells in cystic fibrosis disease modeling and drug discovery

2018 ◽  
Vol 6 (12) ◽  
pp. 707-717
Author(s):  
Massimo Conese ◽  
Elisa Beccia ◽  
Annalucia Carbone ◽  
Stefano Castellani ◽  
Sante Di Gioia ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Stem Cells ◽  
Drug Discovery ◽  
Disease Modeling

scholarly journals Advanced Technologies to Target Cardiac Cell Fate Plasticity for Heart Regeneration

2021 ◽  
Vol 22 (17) ◽  
pp. 9517
Author(s):  
Gianluca Testa ◽  
Giorgia Di Benedetto ◽  
Fabiana Passaro
Keyword(s):  
Cell Fate ◽  
Disease Modeling ◽  
Heart Diseases ◽  
Cellular Reprogramming ◽  
Cardiac Cell ◽  
New Paradigm ◽  
Cardiovascular Research ◽  
Injured Myocardium

The adult human heart can only adapt to heart diseases by starting a myocardial remodeling process to compensate for the loss of functional cardiomyocytes, which ultimately develop into heart failure. In recent decades, the evolution of new strategies to regenerate the injured myocardium based on cellular reprogramming represents a revolutionary new paradigm for cardiac repair by targeting some key signaling molecules governing cardiac cell fate plasticity. While the indirect reprogramming routes require an in vitro engineered 3D tissue to be transplanted in vivo, the direct cardiac reprogramming would allow the administration of reprogramming factors directly in situ, thus holding great potential as in vivo treatment for clinical applications. In this framework, cellular reprogramming in partnership with nanotechnologies and bioengineering will offer new perspectives in the field of cardiovascular research for disease modeling, drug screening, and tissue engineering applications. In this review, we will summarize the recent progress in developing innovative therapeutic strategies based on manipulating cardiac cell fate plasticity in combination with bioengineering and nanotechnology-based approaches for targeting the failing heart.

scholarly journals Human iPS Cell-Derived Patient Tissues and 3D Cell Culture Part 2: Spheroids, Organoids, and Disease Modeling

2019 ◽  
Vol 24 (1) ◽  
pp. 18-27 ◽  
Author(s):  
Richard M. Eglen ◽  
Terry Reisine
Keyword(s):  
Cell Culture ◽  
Drug Discovery ◽  
Disease Modeling ◽  
Cortical Cell ◽  
Neuronal Cell ◽  
3D Cell Culture ◽  
Retinal Cell ◽  
Major Advance ◽  
Ips Cell ◽  
Culture Systems

Human induced pluripotent stem cells (HiPSCs) provide several advantages for drug discovery, but principally they provide a source of clinically relevant tissue. Furthermore, the use of HiPSCs cultured in three-dimensional (3D) systems, as opposed to traditional two-dimensional (2D) culture approaches, better represents the complex tissue architecture in vivo. The use of HiPSCs in 3D spheroid and organoid culture is now growing, but particularly when using myocardial, intestinal enteric nervous system, and retinal cell lines. However, organoid cell culture is perhaps making the most notable impact in research and drug discovery, in which 3D neuronal cell cultures allow direct modeling of cortical cell layering and neuronal circuit activity. Given the specific degeneration seen in discrete neuronal circuitry in Alzheimer’s disease (AD) and Parkinson’s disease (PD), HiPSC culture systems are proving to be a major advance. In the present review, the second part of a two-part review, we discuss novel methods in which 3D cell culture systems (principally organoids) are now being used to provide insights into disease mechanisms. (The use of HiPSCs in target identification was reviewed in detail in Part 1.)

Self-filling microwell arrays (SFMAs) for tumor spheroid formation

Lab on a Chip ◽  
2018 ◽  
Vol 18 (22) ◽  
pp. 3516-3528 ◽  
Author(s):  
Amir Seyfoori ◽  
Ehsan Samiei ◽  
Neda Jalili ◽  
Brent Godau ◽  
Mehdi Rahmanian ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Disease Modeling ◽  
Great Promise ◽  
Tumor Spheroid ◽  
Spheroid Formation ◽  
Tumor Spheroids

Self-filling microwell arrays hold great promise for the production of 3D tumor spheroids and organoids for disease modeling and drug discovery.

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