Convergence of human pluripotent stem cell, organoid, and genome editing technologies

2021 ◽  
pp. 153537022098580
Author(s):  
Lin Wang ◽  
Zhaohui Ye ◽  
Yoon-Young Jang
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Genome Editing ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Three Dimensional ◽  
Experimental Models ◽  
Human Pluripotent Stem Cell ◽  
Research Areas ◽  
Technological Advances

The last decade has seen many exciting technological breakthroughs that greatly expanded the toolboxes for biological and biomedical research, yet few have had more impact than induced pluripotent stem cells and modern-day genome editing. These technologies are providing unprecedented opportunities to improve physiological relevance of experimental models, further our understanding of developmental processes, and develop novel therapies. One of the research areas that benefit greatly from these technological advances is the three-dimensional human organoid culture systems that resemble human tissues morphologically and physiologically. Here we summarize the development of human pluripotent stem cells and their differentiation through organoid formation. We further discuss how genetic modifications, genome editing in particular, were applied to answer basic biological and biomedical questions using organoid cultures of both somatic and pluripotent stem cell origins. Finally, we discuss the potential challenges of applying human pluripotent stem cell and organoid technologies for safety and efficiency evaluation of emerging genome editing tools.

scholarly journals Expression of miRNAs from the Imprinted DLK1/DIO3 Locus Signals the Osteogenic Potential of Human Pluripotent Stem Cells

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1523 ◽  
Author(s):  
Laetitia Barrault ◽  
Jacqueline Gide ◽  
Tingting Qing ◽  
Lea Lesueur ◽  
Jorg Tost ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Osteogenic Differentiation ◽  
Cell Lines ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Human Pluripotent Stem Cells ◽  
Osteogenic Potential ◽  
Human Pluripotent Stem Cell ◽  
Stem Cell Lines

Substantial variations in differentiation properties have been reported among human pluripotent cell lines (hPSC), which could affect their utility and clinical safety. We characterized the variable osteogenic capacity observed between different human pluripotent stem cell lines. By focusing on the miRNA expression profile, we demonstrated that the osteogenic differentiation propensity of human pluripotent stem cell lines could be associated with the methylation status and the expression of miRNAs from the imprinted DLK1/DIO3 locus. More specifically, quantitative analysis of the expression of six different miRNAs of that locus prospectively identified human embryonic stem cells and human-induced pluripotent stem cells with differential osteogenic differentiation capacities. At the molecular and functional levels, we showed that these miRNAs modulated the expression of the activin receptor type 2B and the downstream signal transduction, which impacted osteogenesis. In conclusion, miRNAs of the imprinted DLK1/DIO3 locus appear to have both a predictive value and a functional impact in determining the osteogenic fate of human pluripotent stem cells.

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 Remdesivir but not famotidine inhibits SARS-CoV-2 replication in human pluripotent stem cell-derived intestinal organoids

2020 ◽  
Author(s):  
Jana Krüger ◽  
Rüdiger Groß ◽  
Carina Conzelmann ◽  
Janis A. Müller ◽  
Lennart Koepke ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Gastrointestinal Symptoms ◽  
Cell Types ◽  
Human Pluripotent Stem Cell ◽  
Intestinal Organoids

Gastrointestinal symptoms in COVID-19 are associated with prolonged symptoms and increased severity. We employed human intestinal organoids derived from pluripotent stem cells (PSC-HIOs) to analyze SARS-CoV-2 pathogenesis and to validate efficacy of specific drugs in the gut. Certain, but not all cell types in PSC-HIOs express SARS-CoV-2 entry factors ACE2 and TMPRSS2, rendering them susceptible to SARS-CoV-2 infection. Remdesivir, a promising drug to treat COVID-19, effectively suppressed SARS-CoV-2 infection of PSC-HIOs. In contrast, the histamine-2-blocker famotidine showed no effect. Thus, PSC-HIOs provide an interesting platform to study SARS-CoV-2 infection and to identify or validate drugs.

Manufacturing human pluripotent stem cell derived endothelial cells in scalable and cell-friendly microenvironments

2019 ◽  
Vol 7 (1) ◽  
pp. 373-388
Author(s):  
Haishuang Lin ◽  
Qian Du ◽  
Qiang Li ◽  
Ou Wang ◽  
Zhanqi Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Human Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cell ◽  
Alginate Hydrogel

Alginate hydrogel tubes are designed for the scalable expansion of human pluripotent stem cells and efficient differentiation into endothelial cells.

scholarly journals Human pluripotent stem cell-derived organoids and their potential to reduce the use of animal models in research

2021 ◽  
Vol 4 (s1) ◽  
Author(s):  
Salvatore Simmini ◽  
Allen C. Eaves ◽  
Sharon A. Louis ◽  
Wing Chang
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Animal Models ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Human Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cell ◽  
Tissue Specific ◽  
Organoid Cultures

Efficient and reproducible generation of tissue-specific organoids from Human Pluripotent Stem Cells (hPSCs) represents one of the key tools for reducing the use of animals in research. STEMCELL Technologies is committed to optimizing workflows that efficiently support the generation and maintenance of multiple types of organoid cultures derived from hPSCs.

scholarly journals Intravenously Injected Pluripotent Stem Cell–derived Cells Form Fetomaternal Vasculature and Prevent Miscarriage in Mouse

2020 ◽  
Vol 29 ◽  
pp. 096368972097045
Author(s):  
Atsushi Daimon ◽  
Hirofumi Morihara ◽  
Kiichiro Tomoda ◽  
Natsuko Morita ◽  
Yoshinori Koishi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Intravenous Injection ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Recurrent Miscarriage ◽  
Three Dimensional ◽  
Common Complication ◽  
Dimensional Reconstruction

Miscarriage is the most common complication of pregnancy, and about 1% of pregnant women suffer a recurrence. Using a widely used mouse miscarriage model, we previously showed that intravenous injection of bone marrow (BM)-derived endothelial progenitor cells (EPCs) may prevent miscarriage. However, preparing enough BM-derived EPCs to treat a patient might be problematic. Here, we demonstrated the generation of mouse pluripotent stem cells (PSCs), propagation of sufficient PSC-derived cells with endothelial potential (PSC-EPs), and intravenous injection of the PSC-EPs into the mouse miscarriage model. We found that the injection prevented miscarriage. Three-dimensional reconstruction images of the decidua after tissue cleaning revealed robust fetomaternal neovascularization induced by the PSC-EP injection. Additionally, the injected PSC-EPs directly formed spiral arteries. These findings suggest that intravenous injection of PSC-EPs could become a promising remedy for recurrent miscarriage.

scholarly journals Generation of hepato-biliary-pancreatic organoid from human pluripotent stem cells

2019 ◽  
Author(s):  
Hiroyuki Koike ◽  
Kentaro Iwasawa ◽  
Takanori Takebe
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Three Dimensional ◽  
Human Pluripotent Stem Cell ◽  
Extrinsic Factor ◽  
Interaction Protocol ◽  
Tissue Interactions ◽  
Early Human

Abstract Organogenesis is a complex and inter-connected process, orchestrated by multiple boundary tissue interactions. Here, we established the protocol of the continuous patterning of hepatic, biliary and pancreatic structures from a three-dimensional culture of human pluripotent stem cell (PSC). The boundary interactions between anterior and posterior gut spheroids differentiated from human PSCs enables autonomous emergence of hepato-biliary-pancreatic (HBP) organ domains in the absence of extrinsic factor supply. This anterior-poterior gut interaction protocol can be used to model the early human HBP organogenesis process in vitro.

Effect of geometrical constraints on human pluripotent stem cell nuclei in pluripotency and differentiation

2018 ◽  
Vol 10 (5) ◽  
pp. 278-289 ◽  
Author(s):  
Eleonora Grespan ◽  
Giovanni G. Giobbe ◽  
Florent Badique ◽  
Karine Anselme ◽  
Jürgen Rühe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Human Pluripotent Stem Cell ◽  
Cell Nuclei ◽  
Geometrical Constraints

Pluripotent stem cells are differentiated on microstructured substrates to investigate the nuclear deformability during differentiation and the role of mechanoregulating proteins.

scholarly journals A selective cytotoxic adenovirus vector for concentration of pluripotent stem cells in human pluripotent stem cell-derived neural progenitor cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takamasa Hirai ◽  
Ken Kono ◽  
Rumi Sawada ◽  
Takuya Kuroda ◽  
Satoshi Yasuda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Sensitive Detection ◽  
Quality And Safety

AbstractHighly sensitive detection of residual undifferentiated pluripotent stem cells is essential for the quality and safety of cell-processed therapeutic products derived from human induced pluripotent stem cells (hiPSCs). We previously reported the generation of an adenovirus (Ad) vector and adeno-associated virus vectors that possess a suicide gene, inducible Caspase 9 (iCasp9), which makes it possible to sensitively detect undifferentiated hiPSCs in cultures of hiPSC-derived cardiomyocytes. In this study, we investigated whether these vectors also allow for detection of undifferentiated hiPSCs in preparations of hiPSC-derived neural progenitor cells (hiPSC-NPCs), which have been expected to treat neurological disorders. To detect undifferentiated hiPSCs, the expression of pluripotent stem cell markers was determined by immunostaining and flow cytometry. Using immortalized NPCs as a model, the Ad vector was identified to be the most efficient among the vectors tested in detecting undifferentiated hiPSCs. Moreover, we found that the Ad vector killed most hiPSC-NPCs in an iCasp9-dependent manner, enabling flow cytometry to detect undifferentiated hiPSCs intermingled at a lower concentration (0.002%) than reported previously (0.1%). These data indicate that the Ad vector selectively eliminates hiPSC-NPCs, thus allowing for sensitive detection of hiPSCs. This cytotoxic viral vector could contribute to ensuring the quality and safety of hiPSCs-NPCs for therapeutic use.

scholarly journals Application of the Pluripotent Stem Cells and Genomics in Cardiovascular Research—What We Have Learnt and Not Learnt until Now

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3112
Author(s):  
Michael Simeon ◽  
Seema Dangwal ◽  
Agapios Sachinidis ◽  
Michael Xavier Doss
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Research ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Genome Engineering ◽  
Tourism Industry ◽  
Full Potential ◽  
Cardiovascular Research ◽  
Global Pandemic

Personalized regenerative medicine and biomedical research have been galvanized and revolutionized by human pluripotent stem cells in combination with recent advances in genomics, artificial intelligence, and genome engineering. More recently, we have witnessed the unprecedented breakthrough life-saving translation of mRNA-based vaccines for COVID-19 to contain the global pandemic and the investment in billions of US dollars in space exploration projects and the blooming space-tourism industry fueled by the latest reusable space vessels. Now, it is time to examine where the translation of pluripotent stem cell research stands currently, which has been touted for more than the last two decades to cure and treat millions of patients with severe debilitating degenerative diseases and tissue injuries. This review attempts to highlight the accomplishments of pluripotent stem cell research together with cutting-edge genomics and genome editing tools and, also, the promises that have still not been transformed into clinical applications, with cardiovascular research as a case example. This review also brings to our attention the scientific and socioeconomic challenges that need to be effectively addressed to see the full potential of pluripotent stem cells at the clinical bedside.

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