scholarly journals Blood and Lymphatic Vasculatures On-Chip Platforms and Their Applications for Organ-Specific In Vitro Modeling

Micromachines ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 147 ◽  
Author(s):  
Aria R. Henderson ◽  
Hyoann Choi ◽  
Esak Lee
Keyword(s):  
Cardiovascular System ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
In Vitro Models ◽  
The Body ◽  
Interstitial Tissue ◽  
Organ Specific ◽  
On Chip

The human circulatory system is divided into two complementary and different systems, the cardiovascular and the lymphatic system. The cardiovascular system is mainly concerned with providing nutrients to the body via blood and transporting wastes away from the tissues to be released from the body. The lymphatic system focuses on the transport of fluid, cells, and lipid from interstitial tissue spaces to lymph nodes and, ultimately, to the cardiovascular system, as well as helps coordinate interstitial fluid and lipid homeostasis and immune responses. In addition to having distinct structures from each other, each system also has organ-specific variations throughout the body and both systems play important roles in maintaining homeostasis. Dysfunction of either system leads to devastating and potentially fatal diseases, warranting accurate models of both blood and lymphatic vessels for better studies. As these models also require physiological flow (luminal and interstitial), extracellular matrix conditions, dimensionality, chemotactic biochemical gradient, and stiffness, to better reflect in vivo, three dimensional (3D) microfluidic (on-a-chip) devices are promising platforms to model human physiology and pathology. In this review, we discuss the heterogeneity of both blood and lymphatic vessels, as well as current in vitro models. We, then, explore the organ-specific features of each system with examples in the gut and the brain and the implications of dysfunction of either vasculature in these organs. We close the review with discussions on current in vitro models for specific diseases with an emphasis on on-chip techniques.

Bioengineered in vitro models of leukocyte–vascular interactions

2021 ◽  
Author(s):  
Jaehyun Lee ◽  
Cort B. Breuer ◽  
Esak Lee
Keyword(s):  
Lymphatic Vessels ◽  
In Vitro Models ◽  
Model Systems ◽  
Future Research ◽  
Interstitial Tissue ◽  
Leukocyte Trafficking ◽  
Tissue Space ◽  
Spatiotemporal Analyses

Leukocytes continuously circulate our body through the blood and lymphatic vessels. To survey invaders or abnormalities and defend our body against them, blood-circulating leukocytes migrate from the blood vessels into the interstitial tissue space (leukocyte extravasation) and exit the interstitial tissue space through draining lymphatic vessels (leukocyte intravasation). In the process of leukocyte trafficking, leukocytes recognize and respond to multiple biophysical and biochemical cues in these vascular microenvironments to determine adequate migration and adhesion pathways. As leukocyte trafficking is an essential part of the immune system and is involved in numerous immune diseases and related immunotherapies, researchers have attempted to identify the key biophysical and biochemical factors that might be responsible for leukocyte migration, adhesion, and trafficking. Although intravital live imaging of in vivo animal models has been remarkably advanced and utilized, bioengineered in vitro models that recapitulate complicated in vivo vascular structure and microenvironments are needed to better understand leukocyte trafficking since these in vitro models better allow for spatiotemporal analyses of leukocyte behaviors, decoupling of interdependent biological factors, better controlling of experimental parameters, reproducible experiments, and quantitative cellular analyses. This review discusses bioengineered in vitro model systems that are developed to study leukocyte interactions with complex microenvironments of blood and lymphatic vessels. This review focuses on the emerging concepts and methods in generating relevant biophysical and biochemical cues. Finally, the review concludes with expert perspectives on the future research directions for investigating leukocyte and vascular biology using the in vitro models.

scholarly journals Health Concerns of Various Nanoparticles: A Review of Their in Vitro and in Vivo Toxicity

Nanomaterials ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 634 ◽  
Author(s):  
Marziyeh Ajdary ◽  
Mohammad Moosavi ◽  
Marveh Rahmati ◽  
Mojtaba Falahati ◽  
Mohammad Mahboubi ◽  
...  
Keyword(s):  
Chemical Properties ◽  
Protein Corona ◽  
In Vitro Models ◽  
The Body ◽  
Limiting Factor ◽  
Key Factors ◽  
Cytotoxic Effects ◽  
Physico Chemical

Nanoparticles (NPs) are currently used in diagnosis and treatment of many human diseases, including autoimmune diseases and cancer. However, cytotoxic effects of NPs on normal cells and living organs is a severe limiting factor that hinders their use in clinic. In addition, diversity of NPs and their physico-chemical properties, including particle size, shape, surface area, dispersity and protein corona effects are considered as key factors that have a crucial impact on their safe or toxicological behaviors. Current studies on toxic effects of NPs are aimed to identify the targets and mechanisms of their side effects, with a focus on elucidating the patterns of NP transport, accumulation, degradation, and elimination, in both in vitro and in vitro models. NPs can enter the body through inhalation, skin and digestive routes. Consequently, there is a need for reliable information about effects of NPs on various organs in order to reveal their efficacy and impact on health. This review covers the existing knowledge base on the subject that hopefully prepares us better to address these challenges.

scholarly journals Current Advances in 3D Tissue and Organ Reconstruction

2021 ◽  
Vol 22 (2) ◽  
pp. 830
Author(s):  
Georgia Pennarossa ◽  
Sharon Arcuri ◽  
Teresina De Iorio ◽  
Fulvio Gandolfi ◽  
Tiziana A. L. Brevini
Keyword(s):  
Cell Biology ◽  
Drug Testing ◽  
Three Dimensional ◽  
3D Culture ◽  
In Vitro Models ◽  
The Body ◽  
Cellular Functions ◽  
Culture Systems

Bi-dimensional culture systems have represented the most used method to study cell biology outside the body for over a century. Although they convey useful information, such systems may lose tissue-specific architecture, biomechanical effectors, and biochemical cues deriving from the native extracellular matrix, with significant alterations in several cellular functions and processes. Notably, the introduction of three-dimensional (3D) platforms that are able to re-create in vitro the structures of the native tissue, have overcome some of these issues, since they better mimic the in vivo milieu and reduce the gap between the cell culture ambient and the tissue environment. 3D culture systems are currently used in a broad range of studies, from cancer and stem cell biology, to drug testing and discovery. Here, we describe the mechanisms used by cells to perceive and respond to biomechanical cues and the main signaling pathways involved. We provide an overall perspective of the most recent 3D technologies. Given the breadth of the subject, we concentrate on the use of hydrogels, bioreactors, 3D printing and bioprinting, nanofiber-based scaffolds, and preparation of a decellularized bio-matrix. In addition, we report the possibility to combine the use of 3D cultures with functionalized nanoparticles to obtain highly predictive in vitro models for use in the nanomedicine field.

scholarly journals Iodine-124 PET quantification of organ-specific delivery and expression of NIS-encoding RNA

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthias Miederer ◽  
Stefanie Pektor ◽  
Isabelle Miederer ◽  
Nicole Bausbacher ◽  
Isabell Sofia Keil ◽  
...  
Keyword(s):  
Cell Lines ◽  
Ex Vivo ◽  
Small Animal ◽  
Protein Translation ◽  
The Body ◽  
Small Animal Pet ◽  
Animal Pet ◽  
Organ Specific

Abstract Background RNA-based vaccination strategies tailoring immune response to specific reactions have become an important pillar for a broad range of applications. Recently, the use of lipid-based nanoparticles opened the possibility to deliver RNA to specific sites within the body, overcoming the limitation of rapid degradation in the bloodstream. Here, we have investigated whether small animal PET/MRI can be employed to image the biodistribution of RNA-encoded protein. For this purpose, a reporter RNA coding for the sodium-iodide-symporter (NIS) was in vitro transcribed in cell lines and evaluated for expression. RNA-lipoplex nanoparticles were then assembled by complexing RNA with liposomes at different charge ratios, and functional NIS protein translation was imaged and quantified in vivo and ex vivo by Iodine-124 PET upon intravenous administration in mice. Results NIS expression was detected on the membrane of two cell lines as early as 6 h after transfection and gradually decreased over 48 h. In vivo and ex vivo PET/MRI of anionic spleen-targeting or cationic lung-targeting NIS-RNA lipoplexes revealed a visually detectable rapid increase of Iodine-124 uptake in the spleen or lung compared to control-RNA-lipoplexes, respectively, with minimal background in other organs except from thyroid, stomach and salivary gland. Conclusions The strong organ selectivity and high target-to-background acquisition of NIS-RNA lipoplexes indicate the feasibility of small animal PET/MRI to quantify organ-specific delivery of RNA.

scholarly journals Development and Physiological Functions of the Lymphatic System - Insights from Genetic Studies of Lymphedema

2021 ◽  
Author(s):  
Silvia Martin-Almedina ◽  
Peter Mortimer ◽  
Pia Ostergaard
Keyword(s):  
Lymphatic System ◽  
Imaging Techniques ◽  
The Body ◽  
Genetic Studies ◽  
Disease Mechanisms ◽  
Primary Lymphedema ◽  
And Function ◽  
The Impact

Primary lymphedema is a long-term (chronic) condition characterized by tissue lymph retention and swelling that can affect any part of the body, although it usually develops in the arms or legs. Due to the relevant contribution of the lymphatic system to human physiology, while this review mainly focusses on the clinical and physiological aspects related to the regulation of fluid homeostasis and edema, clinicians need to know that the impact of lymphatic dysfunction with a genetic origin can be wide ranging. Lymphatic gene dysfunction can affect immune function so leading to infection; it can influence cancer development and spread; and it can determine fat transport so impacting on nutrition and obesity. Genetic studies and the development of imaging techniques for the assessment of lymphatic function have enabled the recognition of primary lymphedema as a heterogenic condition in terms of genetic causes and disease mechanisms. In this review, the known biological function of several genes crucial to the development and function of the lymphatic system are used as a basis for understanding normal lymphatic biology. The disease conditions originating from mutations in these genes are discussed together with a detailed clinical description of the phenotype and the up-to-date knowledge in terms of disease mechanisms acquired from in vitro and in vivo research models.

scholarly journals Predicting the In Vivo Performance of Cardiovascular Biomaterials: Current Approaches In Vitro Evaluation of Blood-Biomaterial Interactions

2021 ◽  
Vol 22 (21) ◽  
pp. 11390
Author(s):  
Anne Strohbach ◽  
Raila Busch
Keyword(s):  
Complement Activation ◽  
Clinical Success ◽  
In Vitro Models ◽  
The Body ◽  
Coagulation Cascade ◽  
Biological Processes ◽  
Testing Strategies ◽  
Cardiovascular Implants

The therapeutic efficacy of a cardiovascular device after implantation is highly dependent on the host-initiated complement and coagulation cascade. Both can eventually trigger thrombosis and inflammation. Therefore, understanding these initial responses of the body is of great importance for newly developed biomaterials. Subtle modulation of the associated biological processes could optimize clinical outcomes. However, our failure to produce truly blood compatible materials may reflect our inability to properly understand the mechanisms of thrombosis and inflammation associated with biomaterials. In vitro models mimicking these processes provide valuable insights into the mechanisms of biomaterial-induced complement activation and coagulation. Here, we review (i) the influence of biomaterials on complement and coagulation cascades, (ii) the significance of complement-coagulation interactions for the clinical success of cardiovascular implants, (iii) the modulation of complement activation by surface modifications, and (iv) in vitro testing strategies.

scholarly journals In vitro infection models to study fungal-host interactions

2021 ◽  
Author(s):  
Antonia Last ◽  
Michelle Maurer ◽  
Alexander S Mosig ◽  
Mark S Gresnigt ◽  
Bernhard Hube
Keyword(s):  
Fungal Infections ◽  
In Vitro Models ◽  
Fungal Host ◽  
Host Interactions ◽  
Mucosal Surfaces ◽  
Life Threatening ◽  
On Chip ◽  
Fungal Interactions

Abstract Fungal infections (mycoses) affect over a billion people per year. Approximately two million of these infections are life-threatening, especially for patients with a compromised immune system. Fungi of the genera Aspergillus, Candida, Histoplasma, and Cryptococcus are opportunistic pathogens that contribute to a substantial number of mycoses. To optimize the diagnosis and treatment of mycoses, we need to understand the complex fungal-host interplay during pathogenesis, the fungal attributes causing virulence, and how the host resists infection via immunological defenses. In vitro models can be used to mimic fungal infections of various tissues and organs and the corresponding immune responses at near-physiological conditions. Furthermore, models can include fungal interactions with the host-microbiota to mimic the in vivo situation on skin and mucosal surfaces. This article reviews currently used in vitro models of fungal infections ranging from cell monolayers to microfluidic 3D organ-on-chip (OOC) platforms. We also discuss how OOC models can expand the toolbox for investigating interactions of fungi and their human hosts in the future.

scholarly journals The role of the angiotensins in the pathogenesis of inflammatory joint disease

2021 ◽  
Vol 93 (5) ◽  
pp. 635-639
Author(s):  
Andrei V. Gordeev ◽  
Elena A. Galushko ◽  
Natalia M. Savushkina
Keyword(s):  
Cardiovascular System ◽  
The Body ◽  
Joint Disease ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
In Vivo Experiments ◽  
Anti Inflammatory

The significant humoral effect of the renin-angiotensin-aldosterone system on the regulation of the cardiovascular system and blood pressure has long been widely known. However, the identification and interpretation of new components of renin-angiotensin-aldosterone system in recent years can significantly expand the range of its potential effects on the body. The anti-inflammatory effect of drugs that block angiotensin II and its receptors, including in rheumatic diseases, can become practically significant for General therapists by their effect on reducing the concentration of inflammatory mediators and angiogenesis processes. The organoprotective and anti-inflammatory potentials of drugs that reduce the production of at demonstrated in vitro and in vivo experiments allow us to consider them as first-line angiotropic agents in patients with rheumatoid arthritis, especially in the presence of pathology of the cardiovascular system and kidneys.

Engineering Tools for Studying the Interplay Between Mechanics and Biology in Lymphatic Lipid Transport

2010 ◽  
Author(s):  
J. Brandon Dixon
Keyword(s):  
Immune Cell ◽  
Mechanical Load ◽  
Contractile Function ◽  
Lymphatic Vessels ◽  
Dietary Lipid ◽  
The Body ◽  
Lipid Transport ◽  
Cell Trafficking

The lymphatic vasculature extends through most tissues of the body and plays an essential role in maintaining fluid balance, immune cell trafficking, and lipid transport. Nearly all dietary lipid is transported from the intestine to the circulation via the lymphatic system in the form of triglyceride-rich lipoproteins called chylomicrons. This process can be described through two different mechanisms: 1) entry of the chylomicron into the initial lymphatic vessels of the small intestine, known as lacteals, and 2) the transport of these chylomicrons through the larger collecting lymphatics by a complex and coordinated system of individual contracting vessel units (lymphangions) and valve leaflets. We describe here a set of in vitro and in vivo tools we have developed to study the mechanisms that modulate lipid transport under these two different paradigms and show how these tools are uncovering important biological features involved in these mechanisms. Lymphatic pump function is known to be sensitive to the mechanical load on the vessel as the contractility of isolated vessels has been shown to be both shear and stretch sensitive [1], yet whether these mechanisms are important in regulating contractile function in vivo remains uncertain.

Clinically Relevant Tissue Scale Responses as New Readouts from Organs-on-a-Chip for Precision Medicine

2020 ◽  
Vol 13 (1) ◽  
pp. 111-133 ◽  
Author(s):  
Olivier T. Guenat ◽  
Thomas Geiser ◽  
François Berthiaume
Keyword(s):  
Morphological Changes ◽  
Tissue Level ◽  
In Vitro Models ◽  
Tissue Properties ◽  
Metabolic Functions ◽  
Level Information ◽  
On Chip ◽  
And Function

Organs-on-chips (OOC) are widely seen as being the next generation in vitro models able to accurately recreate the biochemical-physical cues of the cellular microenvironment found in vivo. In addition, they make it possible to examine tissue-scale functional properties of multicellular systems dynamically and in a highly controlled manner. Here we summarize some of the most remarkable examples of OOC technology's ability to extract clinically relevant tissue-level information. The review is organized around the types of OOC outputs that can be measured from the cultured tissues and transferred to clinically meaningful information. First, the creation of functional tissues-on-chip is discussed, followed by the presentation of tissue-level readouts specific to OOC, such as morphological changes, vessel formation and function, tissue properties, and metabolic functions. In each case, the clinical relevance of the extracted information is highlighted.

Sign in / Sign up

Export Citation Format

Share Document