scholarly journals From Spheroids to Organoids: The Next Generation of Model Systems of Human Cardiac Regeneration in a Dish

2021 ◽  
Vol 22 (24) ◽  
pp. 13180
Author(s):  
Mariangela Scalise ◽  
Fabiola Marino ◽  
Luca Salerno ◽  
Eleonora Cianflone ◽  
Claudia Molinaro ◽  
...  
Keyword(s):  
Stem Cells ◽  
Disease Modeling ◽  
Low Cost ◽  
Three Dimensional ◽  
Cardiac Regeneration ◽  
Model Systems ◽  
Cardiovascular Research ◽  
Specific Tissue ◽  
And Migration

Organoids are tiny, self-organized, three-dimensional tissue cultures that are derived from the differentiation of stem cells. The growing interest in the use of organoids arises from their ability to mimic the biology and physiology of specific tissue structures in vitro. Organoids indeed represent promising systems for the in vitro modeling of tissue morphogenesis and organogenesis, regenerative medicine and tissue engineering, drug therapy testing, toxicology screening, and disease modeling. Although 2D cell cultures have been used for more than 50 years, even for their simplicity and low-cost maintenance, recent years have witnessed a steep rise in the availability of organoid model systems. Exploiting the ability of cells to re-aggregate and reconstruct the original architecture of an organ makes it possible to overcome many limitations of 2D cell culture systems. In vitro replication of the cellular micro-environment of a specific tissue leads to reproducing the molecular, biochemical, and biomechanical mechanisms that directly influence cell behavior and fate within that specific tissue. Lineage-specific self-organizing organoids have now been generated for many organs. Currently, growing cardiac organoid (cardioids) from pluripotent stem cells and cardiac stem/progenitor cells remains an open challenge due to the complexity of the spreading, differentiation, and migration of cardiac muscle and vascular layers. Here, we summarize the evolution of biological model systems from the generation of 2D spheroids to 3D organoids by focusing on the generation of cardioids based on the currently available laboratory technologies and outline their high potential for cardiovascular research.

scholarly journals Intestinal Organoids—Current and Future Applications

2016 ◽  
Author(s):  
Andre M. C. Meneses ◽  
Kerstin Schneeberger ◽  
Hedwig S. Kruitwagen ◽  
Louis C. Penning ◽  
Frank G. van Steenbeek ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Intestinal Stem Cells ◽  
Complex Structures ◽  
Technical Advances ◽  
Induced Pluripotent

Recent technical advances in the stem cell field have enabled the in vitro generation of complex structures resembling whole organs termed organoids. Most of these approaches employ culture systems that allow stem cell-derived or tissue progenitor cells to self-organize into three-dimensional (3D)-structures. Since organoids can be grown from various species, organs and from patient-derived induced pluripotent stem cells, they create significant prospects for modelling development and diseases, for toxicology and drug discovery studies, and in the field of regenerative medicine. Here, we report on intestinal stem cells, organoid culture, organoid disease modeling, transplantation, current and future uses of this exciting new insight model to veterinary medicine field.

Generation of human hair-bearing skin organoids from stem cells

2020 ◽  
Author(s):  
Jiyoon Lee ◽  
Karl Koehler
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Hair ◽  
Culture System ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Skin Tissue ◽  
Organoid Culture ◽  
Skin Biology

Abstract Skin is a complex and vulnerable tissue that it is challenging to reconstitute once damaged. Here, we describe a three-dimensional organoid culture system that can generate fully stratified skin with its appendages from human pluripotent stem cells. This in vitro-based skin organoid culture system will benefit investigations into basic skin biology and disease modeling, as well as translational efforts to reconstruct or regenerate skin tissue.

scholarly journals Developments and Opportunities for 3D Bioprinted Organoids

2021 ◽  
Vol 7 (3) ◽  
pp. 364
Author(s):  
Ya Ren ◽  
Xue Yang ◽  
Zhengjiang Ma ◽  
Xin Sun ◽  
Yuxin Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Biology ◽  
Adult Stem Cells ◽  
Materials Science ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Key Characteristics ◽  
And Function ◽  
Further Development

Organoids developed from pluripotent stem cells or adult stem cells are three-dimensional cell cultures possessing certain key characteristics of their organ counterparts, and they can mimic certain biological developmental processes of organs in vitro. Therefore, they have promising applications in drug screening, disease modeling, and regenerative repair of tissues and organs. However, the construction of organoids currently faces numerous challenges, such as breakthroughs in scale size, vascularization, better reproducibility, and precise architecture in time and space. Recently, the application of bioprinting has accelerated the process of organoid construction. In this review, we present current bioprinting techniques and the application of bioinks and summarize examples of successful organoid bioprinting. In the future, a multidisciplinary combination of developmental biology, disease pathology, cell biology, and materials science will aid in overcoming the obstacles pertaining to the bioprinting of organoids. The combination of bioprinting and organoids with a focus on structure and function can facilitate further development of real organs.

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 3094 Production of Engineered Cardiac Tissue for Disease Modeling

2019 ◽  
Vol 3 (s1) ◽  
pp. 18-19
Author(s):  
Morgan Ellis ◽  
Elizabeth Lipke
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cardiac Tissue ◽  
Disease Modeling ◽  
Cardiac Regeneration ◽  
Cardiac Markers ◽  
Cardiac Tissues ◽  
Over Time

OBJECTIVES/SPECIFIC AIMS: Cardiovascular diseases (CVD) is the leading cause of death worldwide in both men and women due to lack of cardiac regeneration after disease or damaged is caused. There are many challenges to studying CVD since native cardiomyocytes cannot be cultured in vitro. With the advancements in biomaterial and pluripotent stem cells research, scientists are now able to produce engineered cardiac tissue models in vitro that mimic the native myocardium. This study shows our methods for producing engineered cardiac tissue with potential applications in cardiac regeneration, disease modeling, and scalable production. METHODS/STUDY POPULATION: In this study, human induced pluripotent stem cells (hiPSCs) were combined with two different photocrosslinkable hybrid biomaterials, poly (ethylene)- glycol fibrinogen (PF) and gelatin methacrylate (GelMa), in various tissue geometries to form 3D human engineered cardiac tissues (3D-hECTs). To study tissue growth and contraction, image and video analysis was performed at specific timepoints. To analyze differentiation efficiency and cell population, flow cytometry was performed using cardiac markers. To evaluate gene expression, qPCR was performed using pluripotency and cardiac specific primers. RESULTS/ANTICIPATED RESULTS: Direct cardiac differentiation of encapsulated hiPSCs resulted in synchronously contracting 3D-hECTs in both biomaterials and all tissue geometries. Spontaneous contractions started on Day 7 and increased in velocity, frequency, and synchronicity over time. 3D-hECTs had high cell viability with > 70% of cells positive for cardiac markers. Engineered tissues showed appropriate temporal changes in gene expression over time with pluripotency gene expression decreasing and cardiac gene expression increasing. DISCUSSION/SIGNIFICANCE OF IMPACT: This study shows the potential for direct differentiation of encapsulated hiPSCs to produce physiologically relevant engineered cardiac tissues. Resulting 3D-hECTS showed features of mature myocardium with appropriate cardiomyocyte populations, mechanical motion, and gene expression. Using this platform, we are able to produce engineered cardiac tissue in a variety of biomaterials and tissue geometries to study new therapeutics, mechanism of disease, and scalable tissue culture.

Growing Self-Organizing Mini-Guts from a Single Intestinal Stem Cell: Mechanism and Applications

Science ◽  
2013 ◽  
Vol 340 (6137) ◽  
pp. 1190-1194 ◽  
Author(s):  
Toshiro Sato ◽  
Hans Clevers
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Self Organization ◽  
Complex Structures ◽  
Organ Identity ◽  
Morphogenesis In Vitro

Recent examples have highlighted how stem cells have the capability to initiate morphogenesis in vitro; that is, to generate complex structures in culture that closely parallel their in vivo counterparts. Lgr5, the receptor for the Wnt-agonistic R-spondins, marks stem cells in multiple adult organs of mice and humans. In R-spondin–based three-dimensional cultures, these Lgr5 stem cells can grow into ever-expanding epithelial organoids that retain their original organ identity. Single Lgr5 stem cells derived from the intestine can be cultured to build epithelial structures that retain hallmarks of the in vivo epithelium. Here, we review the mechanisms that support this notable example of self-organization and discuss applications of this technology for stem cell research, disease modeling (e.g., for colorectal cancer and cystic fibrosis), and regenerative medicine.

scholarly journals Rapid target validation in a Cas9-inducible hiPSC derived kidney model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yasaman Shamshirgaran ◽  
Anna Jonebring ◽  
Anna Svensson ◽  
Isabelle Leefa ◽  
Mohammad Bohlooly-Y ◽  
...  
Keyword(s):  
High Efficiency ◽  
Disease Modeling ◽  
Genetic Manipulation ◽  
Disease Model ◽  
Genetically Engineered ◽  
Model Systems ◽  
Target Validation ◽  
Direct Differentiation ◽  
Kidney Organoids

AbstractRecent advances in induced pluripotent stem cells (iPSCs), genome editing technologies and 3D organoid model systems highlight opportunities to develop new in vitro human disease models to serve drug discovery programs. An ideal disease model would accurately recapitulate the relevant disease phenotype and provide a scalable platform for drug and genetic screening studies. Kidney organoids offer a high cellular complexity that may provide greater insights than conventional single-cell type cell culture models. However, genetic manipulation of the kidney organoids requires prior generation of genetically modified clonal lines, which is a time and labor consuming procedure. Here, we present a methodology for direct differentiation of the CRISPR-targeted cell pools, using a doxycycline-inducible Cas9 expressing hiPSC line for high efficiency editing to eliminate the laborious clonal line generation steps. We demonstrate the versatile use of genetically engineered kidney organoids by targeting the autosomal dominant polycystic kidney disease (ADPKD) genes: PKD1 and PKD2. Direct differentiation of the respective knockout pool populations into kidney organoids resulted in the formation of cyst-like structures in the tubular compartment. Our findings demonstrated that we can achieve > 80% editing efficiency in the iPSC pool population which resulted in a reliable 3D organoid model of ADPKD. The described methodology may provide a platform for rapid target validation in the context of disease modeling.

scholarly journals Light Cross-Linkable Marine Collagen for Coaxial Printing of a 3D Model of Neuromuscular Junction Formation

Biomedicines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 16
Author(s):  
Borja Sanz ◽  
Ane Albillos Sanchez ◽  
Bonnie Tangey ◽  
Kerry Gilmore ◽  
Zhilian Yue ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Neuromuscular Junction ◽  
Disease Transmission ◽  
Low Cost ◽  
Attractive Alternative ◽  
Waste Products ◽  
Environmentally Sustainable ◽  
Zoonotic Disease Transmission ◽  
And Migration

Collagen is a major component of the extracellular matrix (ECM) that modulates cell adhesion, growth, and migration, and has been utilised in tissue engineering applications. However, the common terrestrial sources of collagen carry the risk of zoonotic disease transmission and there are religious barriers to the use of bovine and porcine products in many cultures. Marine based collagens offer an attractive alternative and have so far been under-utilized for use as biomaterials for tissue engineering. Marine collagen can be extracted from fish waste products, therefore industry by-products offer an economical and environmentally sustainable source of collagen. In a handful of studies, marine collagen has successfully been methacrylated to form collagen methacrylate (ColMA). Our work included the extraction, characterization and methacrylation of Red Snapper collagen, optimisation of conditions for neural cell seeding and encapsulation using the unmodified collagen, thermally cross-linked, and the methacrylated collagen with UV-induced cross-linking. Finally, the 3D co-axial printing of neural and skeletal muscle cell cultures as a model for neuromuscular junction (NMJ) formation was investigated. Overall, the results of this study show great potential for a novel NMJ in vitro 3D bioprinted model that, with further development, could provide a low-cost, customizable, scalable and quick-to-print platform for drug screening and to study neuromuscular junction physiology and pathogenesis.

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