scholarly journals Modeling Immunity In Vitro: Slices, Chips, and Engineered Tissues

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Jennifer H. Hammel ◽  
Sophie R. Cook ◽  
Maura C. Belanger ◽  
Jennifer M. Munson ◽  
Rebecca R. Pompano
Keyword(s):  
Disease Modeling ◽  
Environmental Control ◽  
Emerging Diseases ◽  
Patient Specific ◽  
Annual Review ◽  
Publication Date ◽  
Peripheral Tissues ◽  
Engineered Tissues ◽  
3D Microenvironment

Modeling immunity in vitro has the potential to be a powerful tool for investigating fundamental biological questions, informing therapeutics and vaccines, and providing new insight into disease progression. There are two major elements to immunity that are necessary to model: primary immune tissues and peripheral tissues with immune components. Here, we systematically review progress made along three strategies to modeling immunity: ex vivo cultures, which preserve native tissue structure; microfluidic devices, which constitute a versatile approach to providing physiologically relevant fluid flow and environmental control; and engineered tissues, which provide precise control of the 3D microenvironment and biophysical cues. While many models focus on disease modeling, more primary immune tissue models are necessary to advance the field. Moving forward, we anticipate that the expansion of patient-specific models may inform why immunity varies from patient to patient and allow for the rapid comprehension and treatment of emerging diseases, such as coronavirus disease 2019. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 23 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Phenotyping Neurodegeneration in Human iPSCs

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jonathan Li ◽  
Ernest Fraenkel
Keyword(s):  
Neurodegenerative Diseases ◽  
High Throughput Screening ◽  
Data Science ◽  
Disease Modeling ◽  
Patient Specific ◽  
Annual Review ◽  
Publication Date ◽  
Biomedical Data ◽  
Cellular Models ◽  
Human Ipscs

Induced pluripotent stem cell (iPSC) technology holds promise for modeling neurodegenerative diseases. Traditional approaches for disease modeling using animal and cellular models require knowledge of disease mutations. However, many patients with neurodegenerative diseases do not have a known genetic cause. iPSCs offer a way to generate patient-specific models and study pathways of dysfunction in an in vitro setting in order to understand the causes and subtypes of neurodegeneration. Furthermore, iPSC-based models can be used to search for candidate therapeutics using high-throughput screening. Here we review how iPSC-based models are currently being used to further our understanding of neurodegenerative diseases, as well as discuss their challenges and future directions. Expected final online publication date for the Annual Review of Biomedical Data Science, Volume 4 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals The Promise of Human Induced Pluripotent Stem Cells in Dental Research

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Thekkeparambil Chandrabose Srijaya ◽  
Padmaja Jayaprasad Pradeep ◽  
Rosnah Binti Zain ◽  
Sabri Musa ◽  
Noor Hayaty Abu Kasim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Patient Specific ◽  
Dental Research ◽  
Cell Based Therapy ◽  
Induced Pluripotent ◽  
Disease Specific

Induced pluripotent stem cell-based therapy for treating genetic disorders has become an interesting field of research in recent years. However, there is a paucity of information regarding the applicability of induced pluripotent stem cells in dental research. Recent advances in the use of induced pluripotent stem cells have the potential for developing disease-specific iPSC linesin vitrofrom patients. Indeed, this has provided a perfect cell source for disease modeling and a better understanding of genetic aberrations, pathogenicity, and drug screening. In this paper, we will summarize the recent progress of the disease-specific iPSC development for various human diseases and try to evaluate the possibility of application of iPS technology in dentistry, including its capacity for reprogramming some genetic orodental diseases. In addition to the easy availability and suitability of dental stem cells, the approach of generating patient-specific pluripotent stem cells will undoubtedly benefit patients suffering from orodental disorders.

Abstract 518: In Vitro and in vivo Disease Modeling Using Patient Derived iPSCs to Characterize the Calcification Phenotype in Arterial Calcification Due to Deficiency of CD73

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Cynthia St. Hilaire ◽  
Hui Jin ◽  
Yuting Huang ◽  
Dan Yang ◽  
Alejandra Negro ◽  
...  
Keyword(s):  
Vascular Calcification ◽  
Disease Modeling ◽  
Induced Pluripotent Stem Cell ◽  
Dermal Fibroblasts ◽  
In Vivo Studies ◽  
Arterial Calcification ◽  
Patient Specific ◽  
And Control

Objective: The objective of this study was to develop a patient-specific induced pluripotent stem cell (iPSC)-based disease model to understand the process by which CD73-deficiency leads to vascular calcification in the disease, Arterial Calcification due to Deficiency of CD73 (ACDC). Approach & Results: ACDC is an autosomal recessive disease resulting from mutations in the gene encoding for CD73, which converts extracellular AMP to adenosine. CD73-deficiency manifests with tortuosity and vascular calcification of the medial layer of lower-extremity arteries, a pathology associated with diabetes and chronic kidney disease. We previously identified that dermal fibroblasts isolated from ACDC patients calcify in vitro, however in vivo studies of the vasculature are limited, as murine models of CD73 deficiency do not recapitulate the human disease phenotype. Thus, we created iPSCs from ACDC patients and control fibroblasts. ACDC and Control iPSCs form teratomas when injected in immune-compromised mice, however ACDC iPSC teratomas exhibit extensive calcifications. Control and ACDC iPSCs were differentiated down the mesenchymal lineage (MSC) and while there was no difference in chondrogenesis and adipogenesis, ACDC iMSCs underwent osteogenesis sooner than control iPSC, have higher activity of tissue-nonspecific alkaline phosphatase (TNAP), and lower levels of extracellular adenosine. During osteogenic simulation, TNAP activity in ACDC cells significantly increased adenosine levels, however, not to levels needed for functional compensatory stimulation of the adenosine receptors. Inhibition of TNAP with levimisole ablates this increase in adenosine. Treatment with an A2b adenosine receptor (AR) agonist drastically reduced TNAP activity in vitro, and calcification in ACDC teratomas, as did treatment with etidronate, which is currently being tested in a clinical trial on ACDC patients. Conclusions: These results illustrate a pro-osteogenic phenotype in CD73-deficient cells whereby TNAP activity attempts to compensate for CD73 deficiency, but subsequently induces calcification that can be reversed by activation of the A2bAR. The iPSC teratoma model may be used to screen other potential therapeutics for calcification disorders.

Compositional, Structural, and Kinetic Aspects of Lipid Digestion and Bioavailability: In Vitro, In Vivo, and Modeling Approaches

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Sébastien Marze
Keyword(s):  
Annual Review ◽  
Publication Date ◽  
Lipid Digestion ◽  
Modeling Approaches ◽  
Digestion Kinetics ◽  
Food Design ◽  
Structural Aspects ◽  
Development And Evolution

Lipid digestion and bioavailability are usually investigated separately, using different approaches (in vitro, modeling, in vivo). However, a few inclusive studies show that their kinetics are closely linked. Lipid bioavailability kinetics is likely involved in the development and evolution of several diseases, so lipid digestion kinetics could be involved as well and can be modulated by food design or combination. To illustrate this possibility, the compositional and structural aspects of lipid digestion kinetics, as investigated using in vitro and modeling approaches, are presented first. Then, in vivo and mixed approaches enabling the study of both kinetics are reviewed and discussed. Finally, disparate modeling approaches are introduced, and a unifying modeling scheme is proposed, opening new perspectives for understanding the role and interactions of various factors (chemical, physical, and biological) involved in lipid metabolism. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 13 is March 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Abstract 427: A Patient-Specific 3D Bioprinted Platform for in vitro Disease Modeling and Treatment Planning in Pulmonary Vein Stenosis

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Vahid Serpooshan ◽  
Martin L Tomov ◽  
Akaash Kumar ◽  
Bowen Jing ◽  
Sai Raviteja Bhamidipati ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Pulmonary Vein ◽  
Disease Modeling ◽  
Unmet Need ◽  
Cfd Modeling ◽  
Pulmonary Vein Stenosis ◽  
Patient Specific ◽  
Clinical Interventions ◽  
Vein Stenosis

Pulmonary vein stenosis (PVS) is an acute pediatric cardiovascular disease that is always lethal if not treated early. While current clinical interventions (stenting and angioplasties) have shown promising results in treating PVS, they require multiple re-interventions that can lead to re-stenosis and diminished long-term efficacy. Thus, there is an unmet need to develop functional in vitro models of PVS that can serve as a platform to study clinical interventions. Patient-inspired 3D bioprinted tissue models provide a unique model to recapitulate and analyze the complex tissue microenvironment impacted by PVS. Here, we developed perfusable in vitro models of healthy and stenotic pulmonary vein by 3D reconstruction and bioprinting inspired by patient CT data ( Figure 1 ). Models were seeded with human endothelial (ECs) and smooth muscle cells (SMCs) to form a bilayer structure and perfused using a bioreactor to study cell response to stenotic geometry, and to the stent-based treatment. Flow hemodynamics through printed veins were quantified via Computational Fluid Dynamics (CFD) modeling, 4D MRI and 3D Ultrasound Particle Imaging Velocimetry (echo PIV). Cell growth and endothelialization were analyzed. Our work demonstrates the feasibility of bioprinting various cardiovascular cells, to create perfusable, patient-specific vascular constructs that mimic complex in vivo geometries. Deeper understanding of EC-SMC crosstalk mechanisms in in vitro biomimetic models that incorporate tissue-like geometrical, chemical, and biomechanical ques could offer substantial insights for prevention and treatment of PVS, as well as other cardiovascular disease.

Advances in Microbiome Research for Animal Health

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Raquel S. Peixoto ◽  
Derek M. Harkins ◽  
Karen E. Nelson
Keyword(s):  
Current Knowledge ◽  
Animal Health ◽  
Biodiversity Loss ◽  
Emerging Diseases ◽  
Annual Review ◽  
Publication Date ◽  
Toxic Compounds ◽  
Symbiotic Interactions ◽  
Microbiome Research ◽  
And Behavior

Host-associated microbiomes contribute in many ways to the homeostasis of the metaorganism. The microbiome's contributions range from helping to provide nutrition and aiding growth, development, and behavior to protecting against pathogens and toxic compounds. Here we summarize the current knowledge of the diversity and importance of the microbiome to animals, using representative examples of wild and domesticated species. We demonstrate how the beneficial ecological roles of animal-associated microbiomes can be generally grouped into well-defined main categories and how microbe-based alternative treatments can be applied to mitigate problems for both economic and conservation purposes and to provide crucial knowledge about host–microbiota symbiotic interactions. We suggest a Customized Combination of Microbial-Based Therapies to promote animal health and contribute to the practice of sustainable husbandry. We also discuss the ecological connections and threats associated with animal biodiversity loss, microorganism extinction, and emerging diseases, such as the COVID-19 pandemic. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 9 is February 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Translating Basic Research to Animal Agriculture

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
George E. Seidel
Keyword(s):  
Embryo Transfer ◽  
Artificial Insemination ◽  
Companion Animals ◽  
Basic Research ◽  
Annual Review ◽  
Publication Date ◽  
Animal Agriculture ◽  
Vitro Fertilization ◽  
Recent Developments

Procedures to maintain viability of mammalian gametes and embryos in vitro, including cryopreservation, have been exceedingly valuable for my research over the past 55 years. Keeping sperm viable in vitro enables artificial insemination, which, when combined with selective breeding, often is the most effective approach to making rapid genetic change in a population. Superovulation and embryo transfer constitute a parallel approach for amplifying reproduction of female mammals. More recent developments include sexing of semen, in vitro fertilization, cloning by nuclear transfer, and genetic modification of germline cells, tools that are enabled by artificial insemination and/or embryo transfer for implementation. I have been fortunate in being able to contribute to the development of many of the above techniques, and to use them for research and applications for improving animal agriculture. Others have built on this work to circumvent human infertility, assist reproduction of companion animals, and rescue endangered species. It also has been a privilege to teach, mentor, and be mentored in this area. Resulting worldwide friendships have enriched me personally and professionally. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 10 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Phospholipid Scrambling by G Protein–Coupled Receptors

2021 ◽  
Vol 51 (1) ◽  
Author(s):  
George Khelashvili ◽  
Anant K. Menon
Keyword(s):  
G Protein ◽  
Conformational Changes ◽  
Credit Card ◽  
Lipid Membrane ◽  
G Protein Coupled Receptors ◽  
Annual Review ◽  
Publication Date ◽  
Flip Flop ◽  
G Protein Coupled

Rapid flip-flop of phospholipids across the two leaflets of biological membranes is crucial for many aspects of cellular life. The transport proteins that facilitate this process are classified as pump-like flippases and floppases and channel-like scramblases. Unexpectedly, Class A G protein–coupled receptors (GPCRs), a large class of signaling proteins exemplified by the visual receptor rhodopsin and its apoprotein opsin, are constitutively active as scramblases in vitro. In liposomes, opsin scrambles lipids at a unitary rate of >100,000 per second. Atomistic molecular dynamics simulations of opsin in a lipid membrane reveal conformational transitions that expose a polar groove between transmembrane helices 6 and 7. This groove enables transbilayer lipid movement, conceptualized as the swiping of a credit card (lipid) through a card reader (GPCR). Conformational changes that facilitate scrambling are distinct from those associated with GPCR signaling. In this review, we discuss the physiological significance of GPCR scramblase activity and the modes of its regulation in cells. Expected final online publication date for the Annual Review of Biophysics, Volume 51 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Food Matrix and Macronutrient Digestion

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Edoardo Capuano ◽  
Anja E.M. Janssen
Keyword(s):  
Bioactive Compounds ◽  
Annual Review ◽  
Publication Date ◽  
Detailed Knowledge ◽  
Food Matrix ◽  
Peripheral Tissues ◽  
Biochemical Processes ◽  
In Silico Modeling ◽  
Effect Of Food ◽  
Mechanistic Basis

Food digestion may be regarded as a physiological interface between food and health. During digestion, the food matrix is broken down and the component nutrients and bioactive compounds are absorbed through a synergy of mechanical, chemical, and biochemical processes. The food matrix modulates the extent and kinetics to which nutrients and bioactive compounds make themselves available for absorption, hence regulating their concentration profile in the blood and their utilization in peripheral tissues. In this review, we discuss the structural and compositional aspects of food that modulate macronutrient digestibility in each step of digestion. We also discuss in silico modeling approaches to describe the effect of the food matrix on macronutrient digestion. The detailed knowledge of how the food matrix is digested can provide a mechanistic basis to elucidate the complex effect of food on human health and design food with improved functionality. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 12 is March 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Real-Time Infectious Disease Modeling to Inform Emergency Public Health Decision Making

2022 ◽  
Vol 43 (1) ◽  
Author(s):  
Anna Bershteyn ◽  
Hae-Young Kim ◽  
R. Scott Braithwaite
Keyword(s):  
Public Health ◽  
Infectious Disease ◽  
Real Time ◽  
Disease Modeling ◽  
Disease Process ◽  
Annual Review ◽  
Publication Date ◽  
Public Health Response ◽  
Response Options ◽  
Infectious Disease Modeling

Infectious disease transmission is a nonlinear process with complex, sometimes unintuitive dynamics. Modeling can transform information about a disease process and its parameters into quantitative projections that help decision makers compare public health response options. However, modelers face methodologic challenges, data challenges, and communication challenges, which are exacerbated under the time constraints of a public health emergency. We review methods, applications, challenges and opportunities for real-time infectious disease modeling during public health emergencies, with examples drawn from the two deadliest pandemics in recent history: HIV/AIDS and coronavirus disease 2019 (COVID-19). Expected final online publication date for the Annual Review of Public Health, Volume 43 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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