scholarly journals 3D bioprinting of hepatocytes: core–shell structured co-cultures with fibroblasts for enhanced functionality

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rania Taymour ◽  
David Kilian ◽  
Tilman Ahlfeld ◽  
Michael Gelinsky ◽  
Anja Lode
Keyword(s):  
Cell Types ◽  
In Vitro Models ◽  
Core Shell ◽  
Specific Cell ◽  
Cellular Interactions ◽  
Culture Models ◽  
Vitro Model ◽  
And Function ◽  
Different Cell Types

AbstractWith the aim of understanding and recapitulating cellular interactions of hepatocytes in their physiological microenvironment and to generate an artificial 3D in vitro model, a co-culture system using 3D extrusion bioprinting was developed. A bioink based on alginate and methylcellulose (algMC) was first shown to be suitable for bioprinting of hepatocytes; the addition of Matrigel to algMC enhanced proliferation and morphology of them in monophasic scaffolds. Towards a more complex system that allows studying cellular interactions, we applied core–shell bioprinting to establish tailored 3D co-culture models for hepatocytes. The bioinks were specifically functionalized with natural matrix components (based on human plasma, fibrin or Matrigel) and used to co-print fibroblasts and hepatocytes in a spatially defined, coaxial manner. Fibroblasts acted as supportive cells for co-cultured hepatocytes, stimulating the expression of certain biomarkers of hepatocytes like albumin. Furthermore, matrix functionalization positively influenced both cell types in their respective compartments by enhancing their adhesion, viability, proliferation and function. In conclusion, we established a functional co-culture model with independently tunable compartments for different cell types via core–shell bioprinting. This provides the basis for more complex in vitro models allowing co-cultivation of hepatocytes with other liver-specific cell types to closely resemble the liver microenvironment.

scholarly journals An iTSC-derived placental model of SARS-CoV-2 infection unveils ACE2-dependent susceptibility in syncytiotrophoblasts

2021 ◽  
Author(s):  
Joseph Chen ◽  
Jessica A Neil ◽  
Jia Ping Tan ◽  
Raj Rudraraju ◽  
Monika Mohenska ◽  
...  
Keyword(s):  
Viral Entry ◽  
Cell Types ◽  
Specific Cell ◽  
Placental Development ◽  
Health Crisis ◽  
Placental Cell ◽  
Trophoblast Stem Cells ◽  
Vitro Model ◽  
And Function

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) has caused a global health crisis. The primary site of infection is in the respiratory tract but the virus has been associated with a variety of complications involving the gastrointestinal and cardiovascular systems. Since the virus affects a variety of tissue types, there has been interest in understanding SARS-CoV-2 infection in early development and the placenta. The expression of ACE2 or TMPRSS2, both genes critical for viral entry, is present in placental-specific cell types such as extravillous trophoblasts (EVTs) and, especially, syncytiotrophoblasts (STs). The potential of SARS-CoV-2 to infect these placental cells and its effect on placental development and function is still unclear. Furthermore, it is crucial to understand the possible mechanism of vertical transmission of SARS-CoV-2 through the placenta. Here, we developed an in vitro model of SARS-CoV-2 infection of placental cell types using induced trophoblast stem cells (iTSCs). This model allowed us to show that STs but not EVTs are infected. Importantly, infected STs lack the expression of key differentiation genes, lack typically observed differentiated morphology and produce significantly lower human chorionic gonadotropin (HCG) compared to non-infected controls. We also show that an anti-ACE2 antibody prevents SARS-CoV-2 infection and restores normal ST differentiation and function. We highlight the establishment of a platform to study SARS-CoV-2 infection in early placental cell types, which will facilitate investigation of antiviral therapy to protect the placenta during early pregnancy and development.

scholarly journals Modelling the Human Placental Interface In Vitro—A Review

Micromachines ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 884
Author(s):  
Marta Cherubini ◽  
Scott Erickson ◽  
Kristina Haase
Keyword(s):  
Drug Testing ◽  
Cell Types ◽  
In Vitro Models ◽  
Placental Development ◽  
Scientific Challenge ◽  
Induced Pluripotent ◽  
And Function ◽  
And Control

Acting as the primary link between mother and fetus, the placenta is involved in regulating nutrient, oxygen, and waste exchange; thus, healthy placental development is crucial for a successful pregnancy. In line with the increasing demands of the fetus, the placenta evolves throughout pregnancy, making it a particularly difficult organ to study. Research into placental development and dysfunction poses a unique scientific challenge due to ethical constraints and the differences in morphology and function that exist between species. Recently, there have been increased efforts towards generating in vitro models of the human placenta. Advancements in the differentiation of human induced pluripotent stem cells (hiPSCs), microfluidics, and bioprinting have each contributed to the development of new models, which can be designed to closely match physiological in vivo conditions. By including relevant placental cell types and control over the microenvironment, these new in vitro models promise to reveal clues to the pathogenesis of placental dysfunction and facilitate drug testing across the maternal–fetal interface. In this minireview, we aim to highlight current in vitro placental models and their applications in the study of disease and discuss future avenues for these in vitro models.

Mesothelial Cells

2007 ◽  
Vol 27 (2_suppl) ◽  
pp. 110-115 ◽  
Author(s):  
Susan Yung ◽  
Chan Tak Mao
Keyword(s):  
Mesothelial Cell ◽  
In Vitro Models ◽  
Mesothelial Cells ◽  
Dynamic Membrane ◽  
Peritoneal Mesothelial Cells ◽  
Immunohistochemical Markers ◽  
Vitro Model ◽  
And Function

♦ Background The introduction of peritoneal dialysis (PD) as a modality of renal replacement therapy has provoked much interest in the biology of the peritoneal mesothelial cell. Mesothelial cells isolated from omental tissue have immunohistochemical markers that are identical to those of mesothelial stem cells, and omental mesothelial cells can be cultivated in vitro to study changes to their biologic functions in the setting of PD. ♦ Method The present article describes the structure and function of mesothelial cells in the normal peritoneum and details the morphologic changes that occur after the introduction of PD. Furthermore, this article reviews the literature of mesothelial cell culture and the limitations of in vitro studies. ♦ Results The mesothelium is now considered to be a dynamic membrane that plays a pivotal role in the homeostasis of the peritoneal cavity, contributing to the control of fluid and solute transport, inflammation, and wound healing. These functional properties of the mesothelium are compromised in the setting of PD. Cultures of peritoneal mesothelial cells from omental tissue provide a relevant in vitro model that allows researchers to assess specific molecular pathways of disease in a distinct population of cells. Structural and functional attributes of mesothelial cells are discussed in relation to long-term culture, proliferation potential, age of tissue donor, use of human or animal in vitro models, and how the foregoing factors may influence in vitro data. ♦ Conclusions The ability to propagate mesothelial cells in culture has resulted, over the past two decades, in an explosion of mesothelial cell research pertaining to PD and peritoneal disorders. Independent researchers have highlighted the potential use of mesothelial cells as targets for gene therapy or transplantation in the search to provide therapeutic strategies for the preservation of the mesothelium during chemical or bacterial injury.

scholarly journals Mesenchymal Stem Cells as a Promising Cell Source for Integration in Novel In Vitro Models

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1306
Author(s):  
Ann-Kristin Afflerbach ◽  
Mark D. Kiri ◽  
Tahir Detinis ◽  
Ben M. Maoz
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Types ◽  
In Vitro Models ◽  
Cell Source ◽  
Fundamental Research ◽  
Multiple Cell ◽  
Vitro Model

The human-relevance of an in vitro model is dependent on two main factors—(i) an appropriate human cell source and (ii) a modeling platform that recapitulates human in vivo conditions. Recent years have brought substantial advancements in both these aspects. In particular, mesenchymal stem cells (MSCs) have emerged as a promising cell source, as these cells can differentiate into multiple cell types, yet do not raise the ethical and practical concerns associated with other types of stem cells. In turn, advanced bioengineered in vitro models such as microfluidics, Organs-on-a-Chip, scaffolds, bioprinting and organoids are bringing researchers ever closer to mimicking complex in vivo environments, thereby overcoming some of the limitations of traditional 2D cell cultures. This review covers each of these advancements separately and discusses how the integration of MSCs into novel in vitro platforms may contribute enormously to clinical and fundamental research.

scholarly journals Regenerative Neurology and Regenerative Cardiology: Shared Hurdles and Achievements

2022 ◽  
Vol 23 (2) ◽  
pp. 855
Author(s):  
Dinko Mitrečić ◽  
Valentina Hribljan ◽  
Denis Jagečić ◽  
Jasmina Isaković ◽  
Federica Lamberto ◽  
...  
Keyword(s):  
Biomedical Research ◽  
Cell Types ◽  
In Vitro Models ◽  
Medical Systems ◽  
Heart Infarction ◽  
Affected Tissue ◽  
In Vitro Systems ◽  
Different Cell Types ◽  
The Brain

From the first success in cultivation of cells in vitro, it became clear that developing cell and/or tissue specific cultures would open a myriad of new opportunities for medical research. Expertise in various in vitro models has been developing over decades, so nowadays we benefit from highly specific in vitro systems imitating every organ of the human body. Moreover, obtaining sufficient number of standardized cells allows for cell transplantation approach with the goal of improving the regeneration of injured/disease affected tissue. However, different cell types bring different needs and place various types of hurdles on the path of regenerative neurology and regenerative cardiology. In this review, written by European experts gathered in Cost European action dedicated to neurology and cardiology-Bioneca, we present the experience acquired by working on two rather different organs: the brain and the heart. When taken into account that diseases of these two organs, mostly ischemic in their nature (stroke and heart infarction), bring by far the largest burden of the medical systems around Europe, it is not surprising that in vitro models of nervous and heart muscle tissue were in the focus of biomedical research in the last decades. In this review we describe and discuss hurdles which still impair further progress of regenerative neurology and cardiology and we detect those ones which are common to both fields and some, which are field-specific. With the goal to elucidate strategies which might be shared between regenerative neurology and cardiology we discuss methodological solutions which can help each of the fields to accelerate their development.

Transcytosis: Crossing Cellular Barriers

2003 ◽  
Vol 83 (3) ◽  
pp. 871-932 ◽  
Author(s):  
PAMELA L. TUMA ◽  
ANN L. HUBBARD
Keyword(s):  
Cell Types ◽  
In Vitro Models ◽  
Vesicle Traffic ◽  
Fundamental Process ◽  
A Cell ◽  
Multicellular Organisms ◽  
Different Cell Types ◽  
Transport Of Macromolecules

Tuma, Pamela L., and Ann L. Hubbard. Transcytosis: Crossing Cellular Barriers. Physiol Rev 83: 871–932, 2003; 10.1152/physrev.00001.2003.—Transcytosis, the vesicular transport of macromolecules from one side of a cell to the other, is a strategy used by multicellular organisms to selectively move material between two environments without altering the unique compositions of those environments. In this review, we summarize our knowledge of the different cell types using transcytosis in vivo, the variety of cargo moved, and the diverse pathways for delivering that cargo. We evaluate in vitro models that are currently being used to study transcytosis. Caveolae-mediated transcytosis by endothelial cells that line the microvasculature and carry circulating plasma proteins to the interstitium is explained in more detail, as is clathrin-mediated transcytosis of IgA by epithelial cells of the digestive tract. The molecular basis of vesicle traffic is discussed, with emphasis on the gaps and uncertainties in our understanding of the molecules and mechanisms that regulate transcytosis. In our view there is still much to be learned about this fundamental process.

scholarly journals Puumala and Tula Virus Differ in Replication Kinetics and Innate Immune Stimulation in Human Endothelial Cells and Macrophages

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 855 ◽  
Author(s):  
Bourquain ◽  
Bodenstein ◽  
Schürer ◽  
Schaade
Keyword(s):  
Endothelial Cells ◽  
A549 Cells ◽  
Hemorrhagic Fever ◽  
Cell Types ◽  
Innate Immune ◽  
Tula Virus ◽  
Lung Epithelial ◽  
Culture Models ◽  
Different Cell Types

Old world hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) upon zoonotic transmission to humans. In Europe, the Puumala virus (PUUV) is the main causative agent of HFRS. Tula virus (TULV) is also widely distributed in Europe, but there is little knowledge about the pathogenicity of TULV for humans, as reported cases are rare. We studied the replication of TULV in different cell types in comparison to the pathogenic PUUV and analyzed differences in stimulation of innate immunity. While both viruses replicated to a similar extent in interferon (IFN)-deficient Vero E6 cells, TULV replication in human lung epithelial (A549) cells was slower and less efficient when compared to PUUV. In contrast to PUUV, no replication of TULV could be detected in human microvascular endothelial cells and in macrophages. While a strong innate immune response towards PUUV infection was evident at 48 h post infection, TULV infection triggered only a weak IFN response late after infection of A549 cells. Using appropriate in vitro cell culture models for the orthohantavirus infection, we could demonstrate major differences in host cell tropism, replication kinetics, and innate immune induction between pathogenic PUUV and the presumably non- or low-pathogenic TULV that are not observed in Vero E6 cells and may contribute to differences in virulence.

scholarly journals Signaling roles of phosphoinositides in the retina

2020 ◽  
pp. jlr.TR120000806 ◽  
Author(s):  
Raju V. S. Rajala
Keyword(s):  
Cell Types ◽  
Cellular Functions ◽  
Parent Molecule ◽  
Phosphoinositide Signaling ◽  
Wide Range ◽  
The Many ◽  
And Function ◽  
Different Cell Types

The field of phosphoinositide signaling has expanded significantly in recent years. Phosphoinositides (PIs) are universal signaling molecules that directly interact with membrane proteins or with cytosolic proteins containing domains that directly bind phosphoinositides and are recruited to cell membranes. Through the activities of PI kinases and PI phosphatases, seven distinct phosphoinositide lipid molecules are formed from the parent molecule phosphatidylinositol. PI signals regulate a wide range of cellular functions, including cytoskeletal assembly, membrane binding and fusion, ciliogenesis, vesicular transport, and signal transduction. Given the many excellent reviews on phosphoinositide kinases, phosphoinositide phosphatases, and PIs in general, in this review, we discuss recent studies and advances in PI lipid signaling in the retina. We specifically focus on PI lipids from vertebrate (e.g. bovine, rat, mice, toad, and zebrafish) and invertebrate (e.g. drosophila, horseshoe crab, and squid) retinas. We also discuss the importance of PIs revealed from animal models and human diseases, and methods to study PI levels both in vitro and in vivo. We propose that future studies should investigate the function and mechanism of activation of PI-modifying enzymes/phosphatases and further unravel PI regulation and function in the different cell types of the retina.

scholarly journals Characterization of a Human In Vitro Intestinal Model for the Hazard Assessment of Nanomaterials Used in Cancer Immunotherapy

2021 ◽  
Vol 11 (5) ◽  
pp. 2113
Author(s):  
Matthew Gibb ◽  
Sahar H. Pradhan ◽  
Marina R. Mulenos ◽  
Henry Lujan ◽  
James Liu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Microscopic Analysis ◽  
Cell Types ◽  
Seeding Density ◽  
Animal Testing ◽  
Barrier Integrity ◽  
International Agencies ◽  
Culture Models ◽  
And Function

There is momentum in biomedical research to improve the structure and function of in vitro intestinal models that better represent human biology. To build a more comprehensive model, three human cell-types were co-cultured and characterized: i.e., HT29-MTX (intestinal mucous-producing goblet cells), Caco-2 (colon epithelial cells), and Raji B (lymphocytes). Raji B cells transformed a subpopulation of Caco-2 epithelial cells into phagocytic and transcytotic immune-supporting microfold cells (M-cells). A suite of bioassays was implemented to investigate steady-state barrier integrity and cellular communication. The model demonstrated a potentiating effect in metabolism and pro-inflammatory markers. Barrier integrity and cell seeding density seem to play a role in the reliability of endpoint readouts. Microscopic analysis elucidated the importance of multi-cell biomimicry. The data show that monocultures do not have the same characteristics inherent to triple cell culture models. Multiple cell types in an in vitro model produce a better representation of an intact organ and aid in the ability to assess immunomodulatory effects of nanomaterials designed for cancer theranostics after ingestion. As many national and international agencies have stressed, there is a critical need to improve alternative-to-animal strategies for pharmaceuticals in an effort to reduce animal testing.

scholarly journals Role of Lipopolysaccharide, Derived from Various Bacterial Species, in Pulpitis—A Systematic Review

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 138
Author(s):  
Aniela Brodzikowska ◽  
Monika Ciechanowska ◽  
Michał Kopka ◽  
Albert Stachura ◽  
Paweł K. Włodarski
Keyword(s):  
Dental Pulp ◽  
Bacterial Species ◽  
Cell Types ◽  
In Vitro Models ◽  
Pulp Inflammation ◽  
Pulp Cells ◽  
Specific Receptors ◽  
Meta Analyses ◽  
Different Cell Types

Lipopolysaccharide (LPS) is widely used for induction of inflammation in various human tissues, including dental pulp. The purpose of this study was to summarize current medical literature focusing on (1) cell types used by researchers to simulate dental pulp inflammation, (2) LPS variants utilized in experimental settings and how these choices affect the findings. Our study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched for studies reporting outcomes of lipopolysaccharide application on dental pulp cells in vitro using electronic databases: MEDLINE, Web of Science and Scopus. Having gathered data from 115 papers, we aimed to present all known effects LPS has on different cell types present in dental pulp. We focused on specific receptors and particles that are involved in molecular pathways. Our review provides an essential foundation for further research using in vitro models of pulpitis.

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