scholarly journals Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting

2016 ◽  
Vol 113 (8) ◽  
pp. 2206-2211 ◽  
Author(s):  
Xuanyi Ma ◽  
Xin Qu ◽  
Wei Zhu ◽  
Yi-Shuan Li ◽  
Suli Yuan ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Drug Screening ◽  
Disease Modeling ◽  
Umbilical Vein ◽  
Cell Types ◽  
Supporting Cell ◽  
Specific Gene ◽  
3D Bioprinting

The functional maturation and preservation of hepatic cells derived from human induced pluripotent stem cells (hiPSCs) are essential to personalized in vitro drug screening and disease study. Major liver functions are tightly linked to the 3D assembly of hepatocytes, with the supporting cell types from both endodermal and mesodermal origins in a hexagonal lobule unit. Although there are many reports on functional 2D cell differentiation, few studies have demonstrated the in vitro maturation of hiPSC-derived hepatic progenitor cells (hiPSC-HPCs) in a 3D environment that depicts the physiologically relevant cell combination and microarchitecture. The application of rapid, digital 3D bioprinting to tissue engineering has allowed 3D patterning of multiple cell types in a predefined biomimetic manner. Here we present a 3D hydrogel-based triculture model that embeds hiPSC-HPCs with human umbilical vein endothelial cells and adipose-derived stem cells in a microscale hexagonal architecture. In comparison with 2D monolayer culture and a 3D HPC-only model, our 3D triculture model shows both phenotypic and functional enhancements in the hiPSC-HPCs over weeks of in vitro culture. Specifically, we find improved morphological organization, higher liver-specific gene expression levels, increased metabolic product secretion, and enhanced cytochrome P450 induction. The application of bioprinting technology in tissue engineering enables the development of a 3D biomimetic liver model that recapitulates the native liver module architecture and could be used for various applications such as early drug screening and disease modeling.

scholarly journals Pancreatic Progenitors and Organoids as a Prerequisite to Model Pancreatic Diseases and Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Meike Hohwieler ◽  
Martin Müller ◽  
Pierre-Olivier Frappart ◽  
Sandra Heller
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Embryonic Stem ◽  
Cell Types ◽  
Genetically Engineered ◽  
Hereditary Diseases ◽  
Pancreatic Diseases ◽  
Pancreatic Progenitors

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are characterized by their unique capacity to stepwise differentiate towards any particular cell type in an adult organism. Pluripotent stem cells provide a beneficial platform to model hereditary diseases and even cancer development. While the incidence of pancreatic diseases such as diabetes and pancreatitis is increasing, the understanding of the underlying pathogenesis of particular diseases remains limited. Only a few recent publications have contributed to the characterization of human pancreatic development in the fetal stage. Hence, most knowledge of pancreatic specification is based on murine embryology. Optimizing and understanding current in vitro protocols for pancreatic differentiation of ESCs and iPSCs constitutes a prerequisite to generate functional pancreatic cells for better disease modeling and drug discovery. Moreover, human pancreatic organoids derived from pluripotent stem cells, organ-restricted stem cells, and tumor samples provide a powerful technology to model carcinogenesis and hereditary diseases independent of genetically engineered mouse models. Herein, we summarize recent advances in directed differentiation of pancreatic organoids comprising endocrine cell types. Beyond that, we illustrate up-and-coming applications for organoid-based platforms.

scholarly journals 3D bioprinting of functional tissue models for personalized drug screening and in vitro disease modeling

2018 ◽  
Vol 132 ◽  
pp. 235-251 ◽  
Author(s):  
Xuanyi Ma ◽  
Justin Liu ◽  
Wei Zhu ◽  
Min Tang ◽  
Natalie Lawrence ◽  
...  
Keyword(s):  
Drug Screening ◽  
Disease Modeling ◽  
3D Bioprinting ◽  
Functional Tissue ◽  
Tissue Models

scholarly journals Human Organoids for Predictive Toxicology Research and Drug Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Toshikatsu Matsui ◽  
Tadahiro Shinozawa
Keyword(s):  
Stem Cells ◽  
Drug Development ◽  
Disease Modeling ◽  
Cell Types ◽  
Underlying Disease ◽  
Future Research ◽  
Specific Cell ◽  
Predictive Toxicology

Organoids are three-dimensional structures fabricated in vitro from pluripotent stem cells or adult tissue stem cells via a process of self-organization that results in the formation of organ-specific cell types. Human organoids are expected to mimic complex microenvironments and many of the in vivo physiological functions of relevant tissues, thus filling the translational gap between animals and humans and increasing our understanding of the mechanisms underlying disease and developmental processes. In the last decade, organoid research has attracted increasing attention in areas such as disease modeling, drug development, regenerative medicine, toxicology research, and personalized medicine. In particular, in the field of toxicology, where there are various traditional models, human organoids are expected to blaze a new path in future research by overcoming the current limitations, such as those related to differences in drug responses among species. Here, we discuss the potential usefulness, limitations, and future prospects of human liver, heart, kidney, gut, and brain organoids from the viewpoints of predictive toxicology research and drug development, providing cutting edge information on their fabrication methods and functional characteristics.

scholarly journals Human airway lineages derived from pluripotent stem cells reveal the epithelial responses to SARS-CoV-2 infection

2022 ◽  
Author(s):  
Ruobing Wang ◽  
Adam J. Hume ◽  
Mary Lou Beermann ◽  
Chantelle Simone-Roach ◽  
Jonathan Lindstrom-Vautrin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Airway Epithelium ◽  
Disease Modeling ◽  
Inflammatory Responses ◽  
Cell Types ◽  
Severe Illness ◽  
Airway Epithelial ◽  
Airway Cells

There is an urgent need to understand how SARS-CoV-2 infects the airway epithelium and in a subset of individuals leads to severe illness or death. Induced pluripotent stem cells (iPSCs) provide a near limitless supply of human cells that can be differentiated into cell types of interest, including airway epithelium, for disease modeling. We present a human iPSC-derived airway epithelial platform, composed of the major airway epithelial cell types, that is permissive to SARS-CoV-2 infection. Subsets of iPSC-airway cells express the SARS-CoV-2 entry factors ACE2 and TMPRSS2. Multiciliated cells are the primary initial target of SARS-CoV-2 infection. Upon infection with SARS-CoV-2, iPSC-airway cells generate robust interferon and inflammatory responses and treatment with remdesivir or camostat methylate causes a decrease in viral propagation and entry, respectively. In conclusion, iPSC-derived airway cells provide a physiologically relevant in vitro model system to interrogate the pathogenesis of, and develop treatment strategies for, COVID-19 pneumonia.

scholarly journals 3D bioprinting of co-cultured osteogenic spheroids for bone tissue fabrication

2020 ◽  
Author(s):  
Dong Nyoung Heo ◽  
Bugra Ayan ◽  
Madhuri Dey ◽  
Dishary Banerjee ◽  
Hwabok Wee ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Bone Tissue ◽  
Building Blocks ◽  
Specific Gene ◽  
3D Bioprinting ◽  
Cell Seeding ◽  
Native Bone ◽  
Tissue Constructs

AbstractConventional top-down approaches in tissue engineering involving cell seeding on scaffolds have been widely used in bone engineering applications. However, scaffold-based bone tissue constructs have had limited clinical translation due to constrains in supporting scaffolds, minimal flexibility in tuning scaffold degradation, and low achievable cell seeding density as compared with native bone tissue. Here, we demonstrate a pragmatic and scalable bottom-up method, inspired from embryonic developmental biology, to build three-dimensional (3D) scaffold-free constructs using spheroids as building blocks. Human umbilical vein endothelial cells (HUVECs) were introduced to human mesenchymal stem cells (hMSCs) (hMSC/HUVEC) and spheroids were fabricated by an aggregate culture system. Bone tissue was generated by induction of osteogenic differentiation in hMSC/HUVEC spheroids for 10 days, with enhanced osteogenic differentiation and cell viability in the core of the spheroids compared to hMSC-only spheroids. Aspiration-assisted bioprinting (AAB) is a new bioprinting technique which allows precise positioning of spheroids (11% with respect to the spheroid diameter) by employing aspiration to lift individual spheroids and bioprint them onto a hydrogel. AAB facilitated bioprinting of scaffold-free bone tissue constructs using the pre-differentiated hMSC/HUVEC spheroids. These constructs demonstrated negligible changes in their shape for two days after bioprinting owing to the reduced proliferative potential of differentiated stem cells. Bioprinted bone tissues showed interconnectivity with actin-filament formation and high expression of osteogenic and endothelial-specific gene factors. This study thus presents a viable approach for 3D bioprinting of complex-shaped geometries using spheroids as building blocks, which can be used for various applications including but not limited to, tissue engineering, organ-on-a-chip and microfluidic devices, drug screening and, disease modeling.

scholarly journals Human iPSCs and Genome Editing Technologies for Precision Cardiovascular Tissue Engineering

2021 ◽  
Vol 9 ◽  
Author(s):  
Eric K. N. Gähwiler ◽  
Sarah E. Motta ◽  
Marcy Martin ◽  
Bramasta Nugraha ◽  
Simon P. Hoerstrup ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Lines ◽  
Drug Screening ◽  
Genome Engineering ◽  
Molecular Mechanisms ◽  
Disease Modeling ◽  
Cell Types ◽  
Cardiovascular Tissue ◽  
Human Ipscs ◽  
Cardiovascular Tissue Engineering

Induced pluripotent stem cells (iPSCs) originate from the reprogramming of adult somatic cells using four Yamanaka transcription factors. Since their discovery, the stem cell (SC) field achieved significant milestones and opened several gateways in the area of disease modeling, drug discovery, and regenerative medicine. In parallel, the emergence of clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR-Cas9) revolutionized the field of genome engineering, allowing the generation of genetically modified cell lines and achieving a precise genome recombination or random insertions/deletions, usefully translated for wider applications. Cardiovascular diseases represent a constantly increasing societal concern, with limited understanding of the underlying cellular and molecular mechanisms. The ability of iPSCs to differentiate into multiple cell types combined with CRISPR-Cas9 technology could enable the systematic investigation of pathophysiological mechanisms or drug screening for potential therapeutics. Furthermore, these technologies can provide a cellular platform for cardiovascular tissue engineering (TE) approaches by modulating the expression or inhibition of targeted proteins, thereby creating the possibility to engineer new cell lines and/or fine-tune biomimetic scaffolds. This review will focus on the application of iPSCs, CRISPR-Cas9, and a combination thereof to the field of cardiovascular TE. In particular, the clinical translatability of such technologies will be discussed ranging from disease modeling to drug screening and TE applications.

scholarly journals Human airway lineages derived from pluripotent stem cells reveal the epithelial responses to SARS-CoV-2 infection

2021 ◽  
Author(s):  
Ruobing Wang ◽  
Adam Hume ◽  
Mary Lou Beermann ◽  
Chantelle Simone-Roach ◽  
Jonathan Lindstrom-Vautrin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Airway Epithelium ◽  
Disease Modeling ◽  
Inflammatory Responses ◽  
Cell Types ◽  
Severe Illness ◽  
Airway Epithelial ◽  
Airway Cells

There is an urgent need to understand how SARS-CoV-2 infects the airway epithelium and in a subset of individuals leads to severe illness or death. Induced pluripotent stem cells (iPSCs) provide a near limitless supply of human cells that can be differentiated into cell types of interest, including airway epithelium, for disease modeling. We present a human iPSC-derived airway epithelial platform, composed of the major airway epithelial cell types, that is permissive to SARS-CoV-2 infection. Subsets of iPSC-airway cells express the SARS-CoV-2 entry factors ACE2 and TMPRSS2. Multiciliated cells are the primary initial target of SARS-CoV-2 infection. Upon infection with SARS-CoV-2, iPSC-airway cells generate robust interferon and inflammatory responses and treatment with remdesivir or camostat methylate causes a decrease in viral propagation and entry, respectively. In conclusion, iPSC-derived airway cells provide a physiologically relevant in vitro model system to interrogate the pathogenesis of, and develop treatment strategies for, COVID-19 pneumonia.

scholarly journals Bioprinting with human stem cells-laden alginate-gelatin bioink and bioactive glass for tissue engineering

2019 ◽  
Vol 5 (2.2) ◽  
pp. 3 ◽  
Author(s):  
Krishna C. R. Kolan ◽  
Julie A. Semon ◽  
Bradley Bromet ◽  
Delbert E. Day ◽  
Ming C. Leu
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Bioactive Glass ◽  
Three Dimensional ◽  
Cell Types ◽  
3D Models ◽  
Culture Conditions ◽  
3D Bioprinting ◽  
Human Stem Cells ◽  
Tissue Repair And Regeneration

Three-dimensional (3D) bioprinting technologies have shown great potential in the fabrication of 3D models for different human tissues. Stem cells are an attractive cell source in tissue engineering as they can be directed by material and environmental cues to differentiate into multiple cell types for tissue repair and regeneration. In this study, we investigate the viability of human adipose-derived mesenchymal stem cells (ASCs) in alginate-gelatin (Alg-Gel) hydrogel bioprinted with or without bioactive glass. Highly angiogenic borate bioactive glass (13-93B3) in 50 wt% is added to polycaprolactone (PCL) to fabricate scaffolds using a solvent-based extrusion 3D bioprinting technique. The fabricated scaffolds with 12 × 12 × 1 mm3 in overall dimensions are physically characterized, and the glass dissolution from PCL/glass composite over a period of 28 days is studied. Alg-Gel composite hydrogel is used as a bioink to suspend ASCs, and scaffolds are then bioprinted in different configurations: Bioink only, PCL+bioink, and PCL/glass+bioink, to investigate ASC viability. The results indicate the feasibility of the solvent-based bioprinting process to fabricate 3D cellularized scaffolds with more than 80% viability on day 0. The decrease in viability after 7 days due to glass concentration and static culture conditions is discussed. The feasibility of modifying Alg-Gel with 13-93B3 glass for bioprinting is also investigated, and the results are discussed.

scholarly journals Superiority of Adipose-derived CD34+ Cells over Adipose-derived Stem Cells in Promoting Ischamic Tissue Survival

2021 ◽  
Author(s):  
Yan-Jun Liu ◽  
Tian-Yu Zhang ◽  
Poh-Ching Tan ◽  
Yun Xie ◽  
Pei-Qi Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Conditioned Medium ◽  
Umbilical Vein ◽  
Cell Types ◽  
The Other ◽  
Inflammatory Factors ◽  
Tissue Ischemia ◽  
Ischemic Tissue ◽  
Cd34 Cells

Abstract Background: Tissue ischemia usually leads to necrosis and is a threatening condition associated with reconstructive surgery. Promoting the survival of ischemic tissue is critical for improving clinical outcomes. Although various solutions based on stem cells have been reported, there are still limitations to clinical translation. The aim of this study was to develop an effective method to promote the survival of ischemic tissue. Methods: Adipose-derived CD34+ and CD34- cells were obtained by magnetic bead sorting from the stromal vascular faction (SVF). Adipose-derived stem cell (ADSC) were collected by subculture. The angiogenic capacities of CD34+ cells, CD34- cells and ADSC were evaluated in vitro by comparing mRNA and protein expression. Random axial flaps in nude mice were used to evaluate the efficacy of these cells in protecting tissue from necrosis. The effect of these cells in preventing inflammation was also evaluated. Results: Our data suggest that CD34+ cells expressed higher levels of angiogenetic factors and lower levels of inflammatory factors than the other cell types. More vessel branches were formed when human umbilical vein endothelial cells (HUVECs) were treated with conditioned medium from CD34+ cells than conditioned medium from the other cell types. Compared to ADSC, CD34+ cells showed significantly higher efficacy in promoting tissue survival. More CD31+ cells and higher levels of angiogenic factors were observed in tissues from the CD34+ Group than from the other Groups. Lower levels of the proinflammatory factors TNF-α and IL-1b and higher levels of anti-inflammatory factors were found in the CD34+ Group than in the other Groups.Conclusion: Adipose-derived CD34+ cells showed better efficacy in improving ischemic tissue survival than ADSC by reducing tissue inflammation and promoting angiogenesis. CD34+ cells can be obtained easily and may be suitable for clinical applications.

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.

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