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 Cardiac Tissues From Stem Cells

2021 ◽  
Vol 128 (6) ◽  
pp. 775-801
Author(s):  
Giulia Campostrini ◽  
Laura M. Windt ◽  
Berend J. van Meer ◽  
Milena Bellin ◽  
Christine L. Mummery
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Cell Types ◽  
The Body ◽  
Current Status ◽  
Human Pluripotent Stem Cell ◽  
3 Dimensional

The ability of human pluripotent stem cells to form all cells of the body has provided many opportunities to study disease and produce cells that can be used for therapy in regenerative medicine. Even though beating cardiomyocytes were among the first cell types to be differentiated from human pluripotent stem cell, cardiac applications have advanced more slowly than those, for example, for the brain, eye, and pancreas. This is, in part, because simple 2-dimensional human pluripotent stem cell cardiomyocyte cultures appear to need crucial functional cues normally present in the 3-dimensional heart structure. Recent tissue engineering approaches combined with new insights into the dialogue between noncardiomyocytes and cardiomyocytes have addressed and provided solutions to issues such as cardiomyocyte immaturity and inability to recapitulate adult heart values for features like contraction force, electrophysiology, or metabolism. Three-dimensional bioengineered heart tissues are thus poised to contribute significantly to disease modeling, drug discovery, and safety pharmacology, as well as provide new modalities for heart repair. Here, we review the current status of 3-dimensional engineered heart tissues.

scholarly journals The Use of Stem Cell-Derived Organoids in Disease Modeling: An Update

2021 ◽  
Vol 22 (14) ◽  
pp. 7667
Author(s):  
Joseph Azar ◽  
Hisham F. Bahmad ◽  
Darine Daher ◽  
Maya M. Moubarak ◽  
Ola Hadadeh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Disease Modeling ◽  
New Technology ◽  
Three Dimensional ◽  
Cell Types ◽  
Clinical Applications ◽  
In Vitro Drug Screening

Organoids represent one of the most important advancements in the field of stem cells during the past decade. They are three-dimensional in vitro culturing models that originate from self-organizing stem cells and can mimic the in vivo structural and functional specificities of body organs. Organoids have been established from multiple adult tissues as well as pluripotent stem cells and have recently become a powerful tool for studying development and diseases in vitro, drug screening, and host–microbe interaction. The use of stem cells—that have self-renewal capacity to proliferate and differentiate into specialized cell types—for organoids culturing represents a major advancement in biomedical research. Indeed, this new technology has a great potential to be used in a multitude of fields, including cancer research, hereditary and infectious diseases. Nevertheless, organoid culturing is still rife with many challenges, not limited to being costly and time consuming, having variable rates of efficiency in generation and maintenance, genetic stability, and clinical applications. In this review, we aim to provide a synopsis of pluripotent stem cell-derived organoids and their use for disease modeling and other clinical applications.

scholarly journals Brain Organoids: Studying Human Brain Development and Diseases in a Dish

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Jie Xu ◽  
Zhexing Wen
Keyword(s):  
Stem Cell ◽  
High Throughput Screening ◽  
Disease Modeling ◽  
Rapid Development ◽  
Three Dimensional ◽  
Cell Types ◽  
Future Directions ◽  
Human Brain Development ◽  
Basic Biology ◽  
Brain Organoid

With the rapid development of stem cell technology, the advent of three-dimensional (3D) cultured brain organoids has opened a new avenue for studying human neurodevelopment and neurological disorders. Brain organoids are stem-cell-derived 3D suspension cultures that self-assemble into an organized structure with cell types and cytoarchitectures recapitulating the developing brain. In recent years, brain organoids have been utilized in various aspects, ranging from basic biology studies, to disease modeling, and high-throughput screening of pharmaceutical compounds. In this review, we overview the establishment and development of brain organoid technology, its recent progress, and translational applications, as well as existing limitations and future directions.

scholarly journals Mechanical compartmentalization of the intestinal organoid enables crypt folding and collective cell migration

2020 ◽  
Author(s):  
Carlos Pérez-González ◽  
Gerardo Ceada ◽  
Francesco Greco ◽  
Marija Matejcic ◽  
Manuel Gómez-González ◽  
...  
Keyword(s):  
Stem Cell ◽  
Three Dimensional ◽  
Cell Types ◽  
Collective Cell Migration ◽  
Cell Compartment ◽  
Apical Constriction ◽  
Stem Cell Compartment ◽  
Intestinal Organoids ◽  
Physical Forces ◽  
Different Cell Types

Intestinal organoids capture essential features of the intestinal epithelium such as folding of the crypt, spatial compartmentalization of different cell types, and cellular movements from crypt to villus-like domains. Each of these processes and their coordination in time and space requires patterned physical forces that are currently unknown. Here we map the three-dimensional cell-ECM and cell-cell forces in mouse intestinal organoids grown on soft hydrogels. We show that these organoids exhibit a non-monotonic stress distribution that defines mechanical and functional compartments. The stem cell compartment pushes the ECM and folds through apical constriction, whereas the transit amplifying zone pulls the ECM and elongates through basal constriction. Tension measurements establish that the transit amplifying zone isolates mechanically the stem cell compartment and the villus-like domain. A 3D vertex model shows that the shape and force distribution of the crypt can be largely explained by cell surface tensions following the measured apical and basal actomyosin density. Finally, we show that cells are pulled out of the crypt along a gradient of increasing tension, rather than pushed by a compressive stress downstream of mitotic pressure as previously assumed. Our study unveils how patterned forces enable folding and collective migration in the intestinal crypt.

Human neurospheres: From stained sections to three-dimensional assembly

2011 ◽  
Vol 2 (1) ◽  
Author(s):  
Emanuela Monni ◽  
Terenzio Congiu ◽  
Denise Massa ◽  
Roxana Nat ◽  
Andrea Diana
Keyword(s):  
Stem Cell ◽  
Neural Stem Cell ◽  
Inner Core ◽  
Three Dimensional ◽  
Cell Types ◽  
Shape Pattern ◽  
Maturation Stages ◽  
Different Cell Types ◽  
Immunocytochemical Approach

AbstractHuman neurospheres are free-floating spherical clusters generated from a single neural stem cell and comprising cells at different stages of maturation in the neuronal and glial lineages. Although recent findings have disproved the original idea of clonally derived neurospheres according to the paradigm of one stem cell — one neurosphere, they still represent a valid model for growing neural stem cell cultures in vitro. While the immunocytochemical approach to the identification of stem cells, progenitor cells, and mature cells has been extensively used, scant data are available about the ultrastructural arrangement of different cell types within the neurosphere. This paper provides, by means of scanning electron microscopy, some new insights into the three-dimensional assembly of human neurospheres, trying to correlate some parameters such as cell density, shape and growing strategies with the immunolocalization of some antigens such as nestin, GFAP, α-internexin and βIII-tubulin. The major findings from this study are: a) regardless of the stage of in vitro maturation, the growth of the spheres is the result of mitotic divisions producing the aspect of an irregular budding mechanism in the outermost layer look like; b) analysis of the volumetric composition of the inner core has revealed the presence of two alternative shape pattern (pyramidal vs rounded cells) possibly related to both the ongoing maturation stages and GFAP and internexin expression.

scholarly journals Human iPSC-Based Modeling of Central Nerve System Disorders for Drug Discovery

2021 ◽  
Vol 22 (3) ◽  
pp. 1203
Author(s):  
Lu Qian ◽  
Julia TCW
Keyword(s):  
Drug Discovery ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Structural Complexity ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Central Nerve System ◽  
Human Ipscs ◽  
Nerve System

A high-throughput drug screen identifies potentially promising therapeutics for clinical trials. However, limitations that persist in current disease modeling with limited physiological relevancy of human patients skew drug responses, hamper translation of clinical efficacy, and contribute to high clinical attritions. The emergence of induced pluripotent stem cell (iPSC) technology revolutionizes the paradigm of drug discovery. In particular, iPSC-based three-dimensional (3D) tissue engineering that appears as a promising vehicle of in vitro disease modeling provides more sophisticated tissue architectures and micro-environmental cues than a traditional two-dimensional (2D) culture. Here we discuss 3D based organoids/spheroids that construct the advanced modeling with evolved structural complexity, which propels drug discovery by exhibiting more human specific and diverse pathologies that are not perceived in 2D or animal models. We will then focus on various central nerve system (CNS) disease modeling using human iPSCs, leading to uncovering disease pathogenesis that guides the development of therapeutic strategies. Finally, we will address new opportunities of iPSC-assisted drug discovery with multi-disciplinary approaches from bioengineering to Omics technology. Despite technological challenges, iPSC-derived cytoarchitectures through interactions of diverse cell types mimic patients’ CNS and serve as a platform for therapeutic development and personalized precision medicine.

Abstract 17093: Human Neonatal Cardiac Mesenchymal Stem Cells Demonstrates Superior Cardiac Regenerative Abilities Compared to Other Stem Cells

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Muthukumar Gunasekaran ◽  
Rachana Mishra ◽  
Progyaparamita Saha ◽  
Xuebin Fu ◽  
Mohamed Abdullah ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Inflammatory Cytokines ◽  
Cell Types ◽  
Wild Type ◽  
Cell Type ◽  
Anti Inflammatory ◽  
Stem Cell Type

Stem cells transplantation is being explored as an effective therapy for heart diseases. However, majority of stem cell therapies for adult patients with myocardial infarction (MI) had mixed and inconsistent results implying chronological age may influence the effectiveness of regenerative therapies. Therefore, herein, we performed a head-to-head comparison between different, well-studied stem cell types to identify the superior regenerative cell type using rodent MI model.After our standard characterization for each stem cell type (FACS for cell surface markers), 1 million neonatal Cardiac Mesenchymal Stem cells (nMSCs), adult MSCs (aMSCs), adult derived cardiosphere derived cells (aCDCs), umbilical cord derived cells (UCBCs), Bone Marrow derived Mesenchymal Stem cells (BM-MSCs), or cell-free Iscove Modified Dulbecco Medium (IMDM as placebo control) were injected into athymic rat myocardial infarct model. Although all the tested groups significantly improved ejection fraction, nMSCs outperformed other stem cells in cardiac functional recovery. Additionally, nMSCs also showed significant increased cardiac functional recovery compared to aMSCs in wild type rat MI model. Mason trichrome staining with heart sections revealed that decreased fibrosis was evident on nMSCs injection compared to aMSCs in both athymic and wild type rat MI model. Myocardial sections from rats received nMSCs showed significantly reduced M1 macrophages (inflammatory) and increased M2 macrophages (anti-inflammatory) compared with sections from rats having received aMSCs and IMDM control. Pro and anti-inflammatory cytokines analyzed on sera collected on day 2 and 7 revealed that anti-inflammatory cytokine (IL10) was significantly increased and inflammatory cytokines (IL4 and IL12) reduced in nMSCs compared to aMSCs transplanted MI rat model.In conclusion, nMSCs demonstrated superior functional abilities, reduced fibrosis, inflammatory cells and cytokines compared to all the other cell types and with aMSCs demonstrating that nMSCs is an ideal stem cell type for therapeutic application in myocardial infarction.

scholarly journals Mapping single-cell atlases throughout Metazoa unravels cell type evolution

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Alexander J Tarashansky ◽  
Jacob M Musser ◽  
Margarita Khariton ◽  
Pengyang Li ◽  
Detlev Arendt ◽  
...  
Keyword(s):  
Stem Cell ◽  
Single Cell ◽  
Cell Types ◽  
The Self ◽  
Cell Type ◽  
Germ Layers ◽  
Animal Evolution ◽  
Self Assembling ◽  
Animal Phyla ◽  
Cell Data

Comparing single-cell transcriptomic atlases from diverse organisms can elucidate the origins of cellular diversity and assist the annotation of new cell atlases. Yet, comparison between distant relatives is hindered by complex gene histories and diversifications in expression programs. Previously, we introduced the self-assembling manifold (SAM) algorithm to robustly reconstruct manifolds from single-cell data (Tarashansky et al., 2019). Here, we build on SAM to map cell atlas manifolds across species. This new method, SAMap, identifies homologous cell types with shared expression programs across distant species within phyla, even in complex examples where homologous tissues emerge from distinct germ layers. SAMap also finds many genes with more similar expression to their paralogs than their orthologs, suggesting paralog substitution may be more common in evolution than previously appreciated. Lastly, comparing species across animal phyla, spanning mouse to sponge, reveals ancient contractile and stem cell families, which may have arisen early in animal evolution.

scholarly journals SeqEnhDL: sequence-based classification of cell type-specific enhancers using deep learning models

2020 ◽  
Author(s):  
Yupeng Wang ◽  
Rosario B. Jaime-Lara ◽  
Abhrarup Roy ◽  
Ying Sun ◽  
Xinyue Liu ◽  
...  
Keyword(s):  
Neural Network ◽  
Deep Learning ◽  
Dna Sequences ◽  
Cell Types ◽  
Learning Models ◽  
Cell Type ◽  
Coding Sequences ◽  
Sequence Features ◽  
Cell Type Specific ◽  
Different Cell Types

AbstractWe propose SeqEnhDL, a deep learning framework for classifying cell type-specific enhancers based on sequence features. DNA sequences of “strong enhancer” chromatin states in nine cell types from the ENCODE project were retrieved to build and test enhancer classifiers. For any DNA sequence, sequential k-mer (k=5, 7, 9 and 11) fold changes relative to randomly selected non-coding sequences were used as features for deep learning models. Three deep learning models were implemented, including multi-layer perceptron (MLP), Convolutional Neural Network (CNN) and Recurrent Neural Network (RNN). All models in SeqEnhDL outperform state-of-the-art enhancer classifiers including gkm-SVM and DanQ, with regard to distinguishing cell type-specific enhancers from randomly selected non-coding sequences. Moreover, SeqEnhDL is able to directly discriminate enhancers from different cell types, which has not been achieved by other enhancer classifiers. Our analysis suggests that both enhancers and their tissue-specificity can be accurately identified according to their sequence features. SeqEnhDL is publicly available at https://github.com/wyp1125/SeqEnhDL.

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