Modeling of Artificial 3D Human Placenta

2021 ◽  
pp. 1-10
Author(s):  
Rumeysa Tutar ◽  
Betül Çelebi-Saltik
Keyword(s):  
Human Placenta ◽  
Placental Transfer ◽  
Complex Structure ◽  
Cell Types ◽  
Structure And Function ◽  
Technological Advances ◽  
And Function ◽  
Different Cell Types ◽  
Pregnancy And Birth

The placenta is the main organ that allows the fertilized oocyte to develop and mature. It allows the fetus to grow in the prenatal period by transferring oxygen and nutrients between the mother and the fetus. It acts as a basic endocrine organ which creates the physiological changes related to pregnancy and birth in the mother. Removal of wastes and carbon dioxide from the fetus is also achieved by the placenta. It prevents the rejection of the fetus and protects the fetus from harmful effects. Research on the human placenta focuses on understanding the placental structure and function to illuminate the complex structure of this important organ with technological advances. The structure and function of the placental barrier have been investigated with in vitro studies in 2D/3D, and various results have been published comparatively. In this review, we introduce the nature of the placenta with its 3D composition which has been called niche. Different cell types and placental structures are presented. We describe the systems and approaches used in the creation of current 3D placenta, placental transfer models as 3D placental barriers, and micro-engineered 3D placenta on-a-chip to explore complicated placental responses to nanoparticle exposure.

scholarly journals Quantitative assessment of successive carbohydrate additions to the clustered O-glycosylation sites of IgA1 by glycosyltransferases

Glycobiology ◽  
2020 ◽  
Author(s):  
Tyler J Stewart ◽  
Kazuo Takahashi ◽  
Nuo Xu ◽  
Amol Prakash ◽  
Rhubell Brown ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Structure And Function ◽  
Reaction Products ◽  
Technological Advances ◽  
Glycosylation Sites ◽  
Relative Quantitation ◽  
And Function ◽  
Insight Into ◽  
Subsequent Activity

Abstract Mucin-type O-glycosylation occurs on many proteins that transit the Golgi apparatus. These glycans impact structure and function of many proteins and have important roles in cellular biosynthetic processes, signaling, and differentiation. Although recent technological advances have enhanced our ability to profile glycosylation of glycoproteins, limitations in the understanding of the biosynthesis of these glycan structures remain. Some of these limitations stem from the difficulty to track the biosynthetic process of mucin-type O-glycosylation, especially when glycans occur in dense clusters in repeat regions of proteins, such as the mucins or IgA1. Here we describe a series of nanoLC–MS analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1. By utilizing nanoLC–MS relative quantitation of in vitro reaction products, our results provide unique insights into the biosynthesis of clustered IgA1 O-glycans. We have developed a workflow to determine glycoform-specific apparent rates of a polypeptide GalNAc-transferase and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans. In the context of IgA1, these results have potential to provide insight into the molecular mechanisms implicated in the pathogenesis of IgA nephropathy, an autoimmune renal disease involving aberrant IgA1 O-glycosylation. In a broader sense, these methods and workflows are applicable to the studies of the concerted and competing functions of other glycosyltransferases that initiate and extend mucin-type core 1 clustered O-glycosylation.

scholarly journals Understanding the Relevance of DNA Methylation Changes in Immune Differentiation and Disease

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 110 ◽  
Author(s):  
Carlos de la Calle-Fabregat ◽  
Octavio Morante-Palacios ◽  
Esteban Ballestar
Keyword(s):  
Dna Methylation ◽  
Cell Types ◽  
Epigenetic Modifications ◽  
Human Organism ◽  
Cell Phenotype ◽  
Effector Cells ◽  
Technological Advances ◽  
And Function ◽  
Different Cell Types ◽  
External Stimuli

Immune cells are one of the most complex and diverse systems in the human organism. Such diversity implies an intricate network of different cell types and interactions that are dependently interconnected. The processes by which different cell types differentiate from progenitors, mature, and finally exert their function requires an orchestrated succession of molecular processes that determine cell phenotype and function. The acquisition of these phenotypes is highly dependent on the establishment of unique epigenetic profiles that confer identity and function on the various types of effector cells. These epigenetic mechanisms integrate microenvironmental cues into the genome to establish specific transcriptional programs. Epigenetic modifications bridge environment and genome regulation and play a role in human diseases by their ability to modulate physiological programs through external stimuli. DNA methylation is one of the most ubiquitous, stable, and widely studied epigenetic modifications. Recent technological advances have facilitated the generation of a vast amount of genome-wide DNA methylation data, providing profound insights into the roles of DNA methylation in health and disease. This review considers the relevance of DNA methylation to immune system cellular development and function, as well as the participation of DNA methylation defects in immune-mediated pathologies, illustrated by selected paradigmatic diseases.

Spatial epigenetics: linking nuclear structure and function in higher eukaryotes

2010 ◽  
Vol 48 ◽  
pp. 25-43 ◽  
Author(s):  
Dean A. Jackson
Keyword(s):  
Nuclear Structure ◽  
Genetic Information ◽  
Nuclear Architecture ◽  
Cell Types ◽  
Structure And Function ◽  
Chromatin Dynamics ◽  
Functional Product ◽  
Higher Eukaryotes ◽  
And Function ◽  
Different Cell Types

Eukaryotic cells are defined by the genetic information that is stored in their DNA. To function, this genetic information must be decoded. In doing this, the information encoded in DNA is copied first into RNA, during RNA transcription. Primary RNA transcripts are generated within transcription factories, where they are also processed into mature mRNAs, which then pass to the cytoplasm. In the cytoplasm these mRNAs can finally be translated into protein in order to express the genetic information as a functional product. With only rare exceptions, the cells of an individual multicellular eukaryote contain identical genetic information. However, as different genes must be expressed in different cell types to define the structure and function of individual tissues, it is clear that mechanisms must have evolved to regulate gene expression. In higher eukaryotes, mechanisms that regulate the interaction of DNA with the sites where nuclear functions are performed provide one such layer of regulation. In this chapter, I evaluate how a detailed understanding of nuclear structure and chromatin dynamics are beginning to reveal how spatial mechanisms link chromatin structure and function. As these mechanisms operate to modulate the genetic information in DNA, the regulation of chromatin function by nuclear architecture defines the concept of ‘spatial epigenetics’.

Identification of a 40 × 10(3) Mr centromere-associated protein in cultured mammalian cells

1990 ◽  
Vol 97 (4) ◽  
pp. 705-713
Author(s):  
R. Balczon ◽  
M.A. Accavitti ◽  
B.R. Brinkley
Keyword(s):  
Mammalian Cells ◽  
Cell Types ◽  
Immunoblot Analysis ◽  
Structure And Function ◽  
Interphase Nuclei ◽  
Microtubule Associated Proteins ◽  
Associated Proteins ◽  
Cytoplasmic Microtubules ◽  
And Function

Monoclonal antibodies were raised against a complex of proteins that was purified following the crosslinking of tubulin to the centromeres of CHO chromosomes using Lomant's reagent. One of the clones, hybridoma 32–9, produced antibodies that reacted with a 40 × 10(3) Mr protein present in the crosslinked complex. Furthermore, immunoblot analysis demonstrated that the 40 × 10(3) Mr antigen was present in various mammalian cell types from several different species. Indirect immunofluorescence using the antibody produced by clone 32–9 demonstrated that the 40 × 10(3) Mr antigen was associated with both spindle and cytoplasmic microtubules. In addition, centromere/kinetochore staining was detected in metaphase-arrested cells, while staining of prekinetochores in interphase nuclei was not observed. Unlike microtubule-associated proteins and microtubule-dependent ATPases, the 40 × 10(3) Mr protein did not copurify with microtubules when tubules were assembled from cellular homogenates using taxol and either GTP or GTP and AMP-PNP. Instead, the 40 × 10(3) Mr protein remained associated with the insoluble cellular material. The 40 × 10(3) Mr antigen could be released from the insoluble pelleted material by extraction with 1 M NaCl. Once solubilized, the 40 × 10(3) Mr protein was able to copurify with microtubules in assembly assays in vitro. This monoclonal antibody should serve as a valuable probe for studies of centromere/kinetochore structure and function.

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 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 Ultrastructural localization of CMPase, TPPase, and NADPase activity in neurons, satellite cells, and Schwann cells in frog dorsal root ganglia.

1989 ◽  
Vol 37 (2) ◽  
pp. 165-172 ◽  
Author(s):  
G Bennett ◽  
R Hemming
Keyword(s):  
Schwann Cells ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Ultrastructural Localization ◽  
Cell Types ◽  
Structure And Function ◽  
Similar Distribution ◽  
Thiamine Pyrophosphatase ◽  
And Function ◽  
Different Cell Types

Sections of bullfrog dorsal root ganglia were analyzed for cytidine monophosphatase (CMPase), thiamine pyrophosphatase (TPPase), and nicotinamide adenine dinucleotide phosphatase (NADPase) activity, and the distributions of these enzymatic activities were compared with those traditionally found in other cell types (e.g., CMPase: Golgi trans-sacculotubular network; TPPase: trans-Golgi saccule(s); NADPase: intermediate Golgi saccules). In the present study, CMPase activity in neurons was localized mainly to the Golgi trans-sacculotubular network and lysosomes, but sometimes also occurred at the ends of the trans and most distal intermediate Golgi saccules. A similar distribution was found in satellite and Schwann cells. TPPase activity in neurons occurred not only in the trans-Golgi saccule but also in the trans-sacculotubular network, lysosomes, and scattered tubular elements. In satellite and Schwann cells, activity was found in both the trans saccule and trans-sacculotubular network, and substantial activity often appeared in the more distal of the intermediate saccules. NADPase activity in neurons was usually absent from the intermediate Golgi saccules and was confined to the trans-sacculotubular network and lysosomes; however, activity was sometimes also found in the intermediate and/or trans-Golgi saccules. In satellite and Schwann cells, activity appeared consistently in both the trans-sacculotubular network and intermediate saccules, as well as in lysosomes. These distributions, especially in the case of TPPase and NADPase, differ substantially from the most frequently reported localizations of the above enzymes, indicating that the Golgi complex may exhibit considerable plasticity of structure and function in different cell types.

Survival and Function of Islets during Culture

1996 ◽  
Vol 5 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Heather A. Clayton ◽  
Nick J.M. London
Keyword(s):  
Culture Media ◽  
Cell Types ◽  
Continuous Cell Lines ◽  
Culture Techniques ◽  
The Media ◽  
Definition Of ◽  
And Function ◽  
Different Cell Types ◽  
Tissue Culture Techniques

Cell and tissue culture techniques have improved considerably since the first attempts to maintain explants of animal tissue in vitro. The two major developments that have allowed these improvements are the ability to produce continuous cell lines, thus allowing reproducible results to be obtained, and the definition of media for different cell types, thereby reducing the need for supplements of serum and other extraneous extracts. The requirements of islets in culture have been more difficult to define, largely because islets do not proliferate in culture and proliferation rate cannot therefore be used to measure the suitability of the medium. Further difficulties arise because islets are highly metabolically active “mini-organelles.” Although many studies have been undertaken to try and optimize media for the culture islets of Langerhans, the media most commonly used are commercially available media developed for other cell types. There remains ample scope for further refinement of the composition of islet culture media, with the possibility of different media for islets from different species.

scholarly journals Tumors of the Central Nervous System: An Update

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2507
Author(s):  
Carla Mucignat-Caretta
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Structure ◽  
Cell Types ◽  
Structure And Function ◽  
Brain Structure And Function ◽  
The Central Nervous System ◽  
And Function ◽  
Different Cell Types ◽  
The Brain

The brain may be affected by a variety of tumors of different grade, which originate from different cell types at distinct locations, thus impacting on the brain structure and function [...]

scholarly journals The Role of the 3Rs for Understanding and Modeling the Human Placenta

2021 ◽  
Vol 10 (15) ◽  
pp. 3444
Author(s):  
Joana Costa ◽  
Ruth Mackay ◽  
Sophie-Christine de Aguiar Greca ◽  
Alessandro Corti ◽  
Elisabete Silva ◽  
...  
Keyword(s):  
Human Placenta ◽  
Ex Vivo ◽  
Structure And Function ◽  
Collective Impact ◽  
And Function ◽  
Animal Welfare Legislation ◽  
Made In

Modeling the physiology of the human placenta is still a challenge, despite the great number of scientific advancements made in the field. Animal models cannot fully replicate the structure and function of the human placenta and pose ethical and financial hurdles. In addition, increasingly stricter animal welfare legislation worldwide is incentivizing the use of 3R (reduction, refinement, replacement) practices. What efforts have been made to develop alternative models for the placenta so far? How effective are they? How can we improve them to make them more predictive of human pathophysiology? To address these questions, this review aims at presenting and discussing the current models used to study phenomena at the placenta level: in vivo, ex vivo, in vitro and in silico. We describe the main achievements and opportunities for improvement of each type of model and critically assess their individual and collective impact on the pursuit of predictive studies of the placenta in line with the 3Rs and European legislation.

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