scholarly journals Neuromuscular disease modeling on a chip

2020 ◽  
Vol 13 (7) ◽  
pp. dmm044867
Author(s):  
Jeffrey W. Santoso ◽  
Megan L. McCain
Keyword(s):  
Animal Models ◽  
Drug Development ◽  
Neuromuscular Disease ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Neuromuscular Diseases ◽  
Patient Specific ◽  
New Paradigm ◽  
Cell Sources ◽  
On Chip

ABSTRACTOrgans-on-chips are broadly defined as microfabricated surfaces or devices designed to engineer cells into microscale tissues with native-like features and then extract physiologically relevant readouts at scale. Because they are generally compatible with patient-derived cells, these technologies can address many of the human relevance limitations of animal models. As a result, organs-on-chips have emerged as a promising new paradigm for patient-specific disease modeling and drug development. Because neuromuscular diseases span a broad range of rare conditions with diverse etiology and complex pathophysiology, they have been especially challenging to model in animals and thus are well suited for organ-on-chip approaches. In this Review, we first briefly summarize the challenges in neuromuscular disease modeling with animal models. Next, we describe a variety of existing organ-on-chip approaches for neuromuscular tissues, including a survey of cell sources for both muscle and nerve, and two- and three-dimensional neuromuscular tissue-engineering techniques. Although researchers have made tremendous advances in modeling neuromuscular diseases on a chip, the remaining challenges in cell sourcing, cell maturity, tissue assembly and readout capabilities limit their integration into the drug development pipeline today. However, as the field advances, models of healthy and diseased neuromuscular tissues on a chip, coupled with animal models, have vast potential as complementary tools for modeling multiple aspects of neuromuscular diseases and identifying new therapeutic strategies.

scholarly journals Trends in the global organoid technology and industry: from organogenesis in a dish to the commercialization of organoids

Organoid ◽  
2021 ◽  
Vol 1 ◽  
pp. e11
Author(s):  
Hanbyeol Lee ◽  
Jeong Suk Im ◽  
Da Bin Choi ◽  
Dong-Hun Woo
Keyword(s):  
Animal Models ◽  
Drug Development ◽  
Disease Modeling ◽  
Drug Evaluation ◽  
Clinical Stage ◽  
Testing Methods ◽  
Global Trends ◽  
Global Trend ◽  
Animal Data ◽  
The World

Animal models have been standard methods for non-clinical research in drug development for decades. However, many drugs that have shown satisfactory results in non-clinical studies have failed in the clinical stage, presumably because animal data are not fully convertible to human data. Human organoid technology has recently been considered as an alternative to existing non-clinical testing methods, and it could potentially serve a role as a bridge from non-clinical to clinical trials, compensating for the current limitations arising from non-clinical animal models. For this reason, organoid technology is being utilized in various fields of research including academic studies, disease modeling, drug screening, biobanks, and regenerative medicine. In addition, as organoid technology progressively develops, it has been combined with bioengineering to develop applications from manufacturing to drug evaluation platforms, which is leading to a demand for commercialization of organoids for researchers. In accordance with this global trend, the organoid industry continues to grow throughout the world, and organoid research and the market for organoids have been boosted by the demand for efficient and rapid drug development in response to the coronavirus disease 2019 pandemic. In this review, we discuss recent global trends in organoid research, based on tissue types and applications, as well as the organoid market and its prospects.

scholarly journals Kidney Organoid and Microphysiological Kidney Chip Models to Accelerate Drug Development and Reduce Animal Testing

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei-Yang Chen ◽  
Eric A Evangelista ◽  
Jade Yang ◽  
Edward J Kelly ◽  
Catherine K Yeung
Keyword(s):  
Cell Culture ◽  
Kidney Disease ◽  
Drug Development ◽  
Disease Modeling ◽  
Kidney Diseases ◽  
Three Dimensional ◽  
New Drugs ◽  
Electrolyte Balance ◽  
Animal Testing ◽  
Drug Induced

Kidneys are critical for the elimination of many drugs and metabolites via the urine, filtering waste and maintaining proper fluid and electrolyte balance. Emerging technologies incorporating engineered three-dimensional (3D) in vitro cell culture models, such as organoids and microphysiological systems (MPS) culture platforms, have been developed to replicate nephron function, leading to enhanced efficacy, safety, and toxicity evaluation of new drugs and environmental exposures. Organoids are tiny, self-organized three-dimensional tissue cultures derived from stem cells that can include dozens of cell types to replicate the complexity of an organ. In contrast, MPS are highly controlled fluidic culture systems consisting of isolated cell type(s) that can be used to deconvolute mechanism and pathophysiology. Both systems, having their own unique benefits and disadvantages, have exciting applications in the field of kidney disease modeling and therapeutic discovery and toxicology. In this review, we discuss current uses of both hPSC-derived organoids and MPS as pre-clinical models for studying kidney diseases and drug induced nephrotoxicity. Examples such as the use of organoids to model autosomal dominant polycystic kidney disease, and the use of MPS to predict renal clearance and nephrotoxic concentrations of novel drugs are briefly discussed. Taken together, these novel platforms allow investigators to elaborate critical scientific questions. While much work needs to be done, utility of these 3D cell culture technologies has an optimistic outlook and the potential to accelerate drug development while reducing the use of animal testing.

scholarly journals Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip

Micromachines ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 663 ◽  
Author(s):  
Yong Cheol Shin ◽  
Woojung Shin ◽  
Domin Koh ◽  
Alexander Wu ◽  
Yoko M. Ambrosini ◽  
...  
Keyword(s):  
Disease Modeling ◽  
Computational Simulation ◽  
Three Dimensional ◽  
Gastrointestinal Diseases ◽  
Patient Specific ◽  
Epithelial Barrier Function ◽  
Fecal Microbiome ◽  
Particle Mixing ◽  
Dynamic Cell ◽  
Epithelial Layers

The regeneration of the mucosal interface of the human intestine is critical in the host–gut microbiome crosstalk associated with gastrointestinal diseases. The biopsy-derived intestinal organoids provide genetic information of patients with physiological cytodifferentiation. However, the enclosed lumen and static culture condition substantially limit the utility of patient-derived organoids for microbiome-associated disease modeling. Here, we report a patient-specific three-dimensional (3D) physiodynamic mucosal interface-on-a-chip (PMI Chip) that provides a microphysiological intestinal milieu under defined biomechanics. The real-time imaging and computational simulation of the PMI Chip verified the recapitulation of non-linear luminal and microvascular flow that simulates the hydrodynamics in a living human gut. The multiaxial deformations in a convoluted microchannel not only induced dynamic cell strains but also enhanced particle mixing in the lumen microchannel. Under this physiodynamic condition, an organoid-derived epithelium obtained from the patients diagnosed with Crohn’s disease, ulcerative colitis, or colorectal cancer independently formed 3D epithelial layers with disease-specific differentiations. Moreover, co-culture with the human fecal microbiome in an anoxic–oxic interface resulted in the formation of stochastic microcolonies without a loss of epithelial barrier function. We envision that the patient-specific PMI Chip that conveys genetic, epigenetic, and environmental factors of individual patients will potentially demonstrate the pathophysiological dynamics and complex host–microbiome crosstalk to target a patient-specific disease modeling.

scholarly journals Applications of 3D Bioprinted-Induced Pluripotent Stem Cells in Healthcare

2020 ◽  
Vol 6 (4) ◽  
Author(s):  
Soja Saghar Soman ◽  
Sanjairaj Vijayavenkataraman
Keyword(s):  
Disease Modeling ◽  
Three Dimensional ◽  
Induced Pluripotent Stem Cell ◽  
Drug Efficacy ◽  
Patient Specific ◽  
Precision Oncology ◽  
Human Tissues ◽  
3D Bioprinting ◽  
3D Print ◽  
Induced Pluripotent

Induced pluripotent stem cell (iPSC) technology and advancements in three-dimensional (3D) bioprinting technology enable scientists to reprogram somatic cells to iPSCs and 3D print iPSC-derived organ constructs with native tissue architecture and function. iPSCs and iPSC-derived cells suspended in hydrogels (bioinks) allow to print tissues and organs for downstream medical applications. The bioprinted human tissues and organs are extremely valuable in regenerative medicine as bioprinting of autologous iPSC-derived organs eliminates the risk of immune rejection with organ transplants. Disease modeling and drug screening in bioprinted human tissues will give more precise information on disease mechanisms, drug efficacy, and drug toxicity than experimenting on animal models. Bioprinted iPSC-derived cancer tissues will aid in the study of early cancer development and precision oncology to discover patient-specific drugs. In this review, we present a brief summary of the combined use of two powerful technologies, iPSC technology, and 3D bioprinting in health-care applications.

scholarly journals Compliant 3D frameworks instrumented with strain sensors for characterization of millimeter-scale engineered muscle tissues

2021 ◽  
Vol 118 (19) ◽  
pp. e2100077118
Author(s):  
Hangbo Zhao ◽  
Yongdeok Kim ◽  
Heling Wang ◽  
Xin Ning ◽  
Chenkai Xu ◽  
...  
Keyword(s):  
Disease Modeling ◽  
Three Dimensional ◽  
High Sensitivity ◽  
Strain Sensors ◽  
High Temporal Resolution ◽  
On Chip ◽  
Contractile Forces ◽  
Traditional Approaches ◽  
And Control

Tissue-on-chip systems represent promising platforms for monitoring and controlling tissue functions in vitro for various purposes in biomedical research. The two-dimensional (2D) layouts of these constructs constrain the types of interactions that can be studied and limit their relevance to three-dimensional (3D) tissues. The development of 3D electronic scaffolds and microphysiological devices with geometries and functions tailored to realistic 3D tissues has the potential to create important possibilities in advanced sensing and control. This study presents classes of compliant 3D frameworks that incorporate microscale strain sensors for high-sensitivity measurements of contractile forces of engineered optogenetic muscle tissue rings, supported by quantitative simulations. Compared with traditional approaches based on optical microscopy, these 3D mechanical frameworks and sensing systems can measure not only motions but also contractile forces with high accuracy and high temporal resolution. Results of active tension force measurements of engineered muscle rings under different stimulation conditions in long-term monitoring settings for over 5 wk and in response to various chemical and drug doses demonstrate the utility of such platforms in sensing and modulation of muscle and other tissues. Possibilities for applications range from drug screening and disease modeling to biohybrid robotic engineering.

scholarly journals Human Three-Dimensional Hepatic Models: Cell Type Variety and Corresponding Applications

2021 ◽  
Vol 9 ◽  
Author(s):  
Qianqian Xu
Keyword(s):  
Stem Cell ◽  
Drug Development ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Cell Types ◽  
Hepatic Cell ◽  
Human Hepatocytes ◽  
Hepatic Cancer ◽  
Cell Type ◽  
Different Cell Types

Owing to retained hepatic phenotypes and functions, human three-dimensional (3D) hepatic models established with diverse hepatic cell types are thought to recoup the gaps in drug development and disease modeling limited by a conventional two-dimensional (2D) cell culture system and species-specific variability in drug metabolizing enzymes and transporters. Primary human hepatocytes, human hepatic cancer cell lines, and human stem cell–derived hepatocyte-like cells are three main hepatic cell types used in current models and exhibit divergent hepatic phenotypes. Primary human hepatocytes derived from healthy hepatic parenchyma resemble in vivo–like genetic and metabolic profiling. Human hepatic cancer cell lines are unlimitedly reproducible and tumorigenic. Stem cell–derived hepatocyte-like cells derived from patients are promising to retain the donor’s genetic background. It has been suggested in some studies that unique properties of cell types endue them with benefits in different research fields of in vitro 3D modeling paradigm. For instance, the primary human hepatocyte was thought to be the gold standard for hepatotoxicity study, and stem cell–derived hepatocyte-like cells have taken a main role in personalized medicine and regenerative medicine. However, the comprehensive review focuses on the hepatic cell type variety, and corresponding applications in 3D models are sparse. Therefore, this review summarizes the characteristics of different cell types and discusses opportunities of different cell types in drug development, liver disease modeling, and liver transplantation.

scholarly journals Peristaltic on-chip pump for tunable media circulation and whole blood perfusion in PDMS-free organ-on-chip and organ-disc systems

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Stefan Schneider ◽  
Marvin Bubeck ◽  
Julia Rogal ◽  
Huub Weener ◽  
Cristhian Rojas ◽  
...  
Keyword(s):  
Animal Models ◽  
Personalized Medicine ◽  
Drug Development ◽  
Whole Blood ◽  
Blood Perfusion ◽  
Promising Tool ◽  
Cell Assays ◽  
Conventional Animal ◽  
On Chip

Organ-on-Chip (OoC) systems have become a promising tool for personalized medicine and drug development with advantages over conventional animal models and cell assays. However, the utility of OoCs in industrial...

Transplantation of Adipose-derived Cells for Periodontal Regeneration: A Systematic Review

2019 ◽  
Vol 14 (6) ◽  
pp. 504-518 ◽  
Author(s):  
Dilcele Silva Moreira Dziedzic ◽  
Bassam Felipe Mogharbel ◽  
Priscila Elias Ferreira ◽  
Ana Carolina Irioda ◽  
Katherine Athayde Teixeira de Carvalho
Keyword(s):  
Systematic Review ◽  
Animal Models ◽  
Platelet Rich Plasma ◽  
Periodontal Regeneration ◽  
In Vitro Studies ◽  
In Vivo Studies ◽  
Cell Sources ◽  
Study Designs

This systematic review evaluated the transplantation of cells derived from adipose tissue for applications in dentistry. SCOPUS, PUBMED and LILACS databases were searched for in vitro studies and pre-clinical animal model studies using the keywords “ADIPOSE”, “CELLS”, and “PERIODONTAL”, with the Boolean operator “AND”. A total of 160 titles and abstracts were identified, and 29 publications met the inclusion criteria, 14 in vitro and 15 in vivo studies. In vitro studies demonstrated that adipose- derived cells stimulate neovascularization, have osteogenic and odontogenic potential; besides adhesion, proliferation and differentiation on probable cell carriers. Preclinical studies described improvement of bone and periodontal healing with the association of adipose-derived cells and the carrier materials tested: Platelet Rich Plasma, Fibrin, Collagen and Synthetic polymer. There is evidence from the current in vitro and in vivo data indicating that adipose-derived cells may contribute to bone and periodontal regeneration. The small quantity of studies and the large variation on study designs, from animal models, cell sources and defect morphology, did not favor a meta-analysis. Additional studies need to be conducted to investigate the regeneration variability and the mechanisms of cell participation in the processes. An overview of animal models, cell sources, and scaffolds, as well as new perspectives are provided for future bone and periodontal regeneration study designs.

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.

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