scholarly journals Disease modeling of pulmonary fibrosis using human pluripotent stem cell-derived alveolar organoids

2021 ◽  
Author(s):  
Takahiro Suezawa ◽  
Shuhei Kanagaki ◽  
Keita Moriguchi ◽  
Atsushi Masui ◽  
Kazuhisa Nakao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pulmonary Fibrosis ◽  
Pluripotent Stem Cell ◽  
Disease Modeling ◽  
Human Pluripotent Stem Cell

scholarly journals Perspective on human pluripotent stem cell‐derived cardiomyocytes in heart disease modeling and repair

2020 ◽  
Vol 9 (10) ◽  
pp. 1121-1128
Author(s):  
Qiang Li ◽  
Jia Wang ◽  
Qiang Wu ◽  
Nan Cao ◽  
Huang‐Tian Yang
Keyword(s):  
Stem Cell ◽  
Heart Disease ◽  
Pluripotent Stem Cell ◽  
Disease Modeling ◽  
Human Pluripotent Stem Cell

scholarly journals In Vivo Assessment of Size-Selective Glomerular Sieving in Transplanted Human Induced Pluripotent Stem Cell–Derived Kidney Organoids

2020 ◽  
Vol 31 (5) ◽  
pp. 921-929 ◽  
Author(s):  
Cathelijne W. van den Berg ◽  
Angela Koudijs ◽  
Laila Ritsma ◽  
Ton J. Rabelink
Keyword(s):  
Stem Cell ◽  
Molecular Mass ◽  
Glomerular Filtration ◽  
Pluripotent Stem Cell ◽  
Disease Modeling ◽  
Left Kidney ◽  
Kidney Tissue ◽  
Human Pluripotent Stem Cell ◽  
Filtration Barrier ◽  
Kidney Organoids

BackgroundThe utility of kidney organoids in regenerative medicine will rely on the functionality of the glomerular and tubular structures in these tissues. Recent studies have demonstrated the vascularization and subsequent maturation of human pluripotent stem cell–derived kidney organoids after renal subcapsular transplantation. This raises the question of whether the glomeruli also become functional upon transplantation.MethodsWe transplanted kidney organoids under the renal capsule of the left kidney in immunodeficient mice followed by the implantation of a titanium imaging window on top of the kidney organoid. To assess glomerular function in the transplanted human pluripotent stem cell–derived kidney tissue 1, 2, and 3 weeks after transplantation, we applied high-resolution intravital multiphoton imaging through the imaging window during intravenous infusion of fluorescently labeled low and high molecular mass dextran molecules or albumin.ResultsAfter vascularization, glomerular structures in the organoid displayed dextran and albumin size selectivity across their glomerular filtration barrier. We also observed evidence of proximal tubular dextran reuptake.ConclusionsOur results demonstrate that human pluripotent stem cell–derived glomeruli can develop an appropriate barrier function and discriminate between molecules of varying size. These characteristics together with tubular presence of low molecular mass dextran provide clear evidence of functional filtration. This approach to visualizing glomerular filtration function will be instrumental for translation of organoid technology for clinical applications as well as for disease modeling.

scholarly journals Human Pluripotent Stem Cell-Derived Cardiac Cells: Application in Disease Modeling, Cell Therapy, and Drug Discovery

2021 ◽  
Vol 9 ◽  
Author(s):  
Juan Huang ◽  
Qi Feng ◽  
Li Wang ◽  
Bingying Zhou
Keyword(s):  
Stem Cell ◽  
Drug Discovery ◽  
Cell Therapy ◽  
Pluripotent Stem Cell ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Cardiac Cells ◽  
Cardiac Diseases ◽  
Human Pluripotent Stem Cell ◽  
Species Specific

Cardiac diseases are the leading cause of deaths worldwide; however, to date, there has been limited progress in the development of therapeutic options for these conditions. Animal models have been the most extensively studied methods to recapitulate a wide variety of cardiac diseases, but these models exhibit species-specific differences in physiology, metabolism and genetics, which lead to inaccurate and unpredictable drug safety and efficacy results, resulting in drug attrition. The development of human pluripotent stem cell (hPSC) technology in theory guarantees an unlimited source of human cardiac cells. These hPSC-derived cells are not only well suited for traditional two-dimensional (2-D) monoculture, but also applicable to more complex systems, such as three-dimensional (3-D) organoids, tissue engineering and heart on-a-chip. In this review, we discuss the application of hPSCs in heart disease modeling, cell therapy, and next-generation drug discovery. While the hPSC-related technologies still require optimization, their advances hold promise for revolutionizing cell-based therapies and drug discovery.

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 Generating ring-shaped engineered heart tissues from ventricular and atrial human pluripotent stem cell-derived cardiomyocytes

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Idit Goldfracht ◽  
Stephanie Protze ◽  
Assad Shiti ◽  
Noga Setter ◽  
Amit Gruber ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Drug Testing ◽  
Disease Modeling ◽  
Single Cells ◽  
Human Pluripotent Stem Cell ◽  
Force Measurements ◽  
Mixed Cell ◽  
Collagen Hydrogel ◽  
Engineered Heart Tissues

AbstractThe functions of the heart are achieved through coordination of different cardiac cell subtypes (e.g., ventricular, atrial, conduction-tissue cardiomyocytes). Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) offer unique opportunities for cardiac research. Traditional studies using these cells focused on single-cells and utilized mixed cell populations. Our goal was to develop clinically-relevant engineered heart tissues (EHTs) comprised of chamber-specific hPSC-CMs. Here we show that such EHTs can be generated by directing hPSCs to differentiate into ventricular or atrial cardiomyocytes, and then embedding these cardiomyocytes in a collagen-hydrogel to create chamber-specific, ring-shaped, EHTs. The chamber-specific EHTs display distinct atrial versus ventricular phenotypes as revealed by immunostaining, gene-expression, optical assessment of action-potentials and conduction velocity, pharmacology, and mechanical force measurements. We also establish an atrial EHT-based arrhythmia model and confirm its usefulness by applying relevant pharmacological interventions. Thus, our chamber-specific EHT models can be used for cardiac disease modeling, pathophysiological studies and drug testing.

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