scholarly journals Rapid 3D BioPrinting of a human iPSC-derived cardiac micro-tissue for high-throughput drug testing

2021 ◽  
Vol 3 ◽  
pp. 100007
Author(s):  
Kathleen L. Miller ◽  
Yi Xiang ◽  
Claire Yu ◽  
Jacob Pustelnik ◽  
Jerry Wu ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Testing ◽  
3D Bioprinting ◽  
Human Ipsc

scholarly journals 3D bioprinting: novel approaches for engineering complex human tissue equivalents and drug testing

2021 ◽  
Author(s):  
Judith Hagenbuchner ◽  
Daniel Nothdurfter ◽  
Michael J. Ausserlechner
Keyword(s):  
Human Tissue ◽  
Intracellular Signaling ◽  
Mammalian Cells ◽  
Drug Testing ◽  
Patient Specific ◽  
Attractive Alternative ◽  
3D Bioprinting ◽  
Tissue Equivalents ◽  
Common Strategy ◽  
Specific Tissue

Abstract Conventional approaches in drug development involve testing on 2D-cultured mammalian cells, followed by experiments in rodents. Although this is the common strategy, it has significant drawbacks: in 2D cell culture with human cells, the cultivation at normoxic conditions on a plastic or glass surface is an artificial situation that significantly changes energy metabolism, shape and intracellular signaling, which in turn directly affects drug response. On the other hand, rodents as the most frequently used animal models have evolutionarily separated from primates about 100 million years ago, with significant differences in physiology, which frequently leads to results not reproducible in humans. As an alternative, spheroid technology and micro-organoids have evolved in the last decade to provide 3D context for cells similar to native tissue. However, organoids used for drug testing are usually just in the 50–100 micrometers range and thereby too small to mimic micro-environmental tissue conditions such as limited nutrient and oxygen availability. An attractive alternative offers 3D bioprinting as this allows fabrication of human tissue equivalents from scratch with hollow structures for perfusion and strict spatiotemporal control over the deposition of cells and extracellular matrix proteins. Thereby, tissue surrogates with defined geometry are fabricated that offer unique opportunities in exploring cellular cross-talk, mechanobiology and morphogenesis. These tissue-equivalents are also very attractive tools in drug testing, as bioprinting enables standardized production, parallelization, and application-tailored design of human tissue, of human disease models and patient-specific tissue avatars. This review, therefore, summarizes recent advances in 3D bioprinting technology and its application for drug screening.

3D Bioprinting a human iPSC-derived MSC-loaded scaffold for repair of the uterine endometrium

2020 ◽  
Vol 116 ◽  
pp. 268-284
Author(s):  
Wanqing Ji ◽  
Bo Hou ◽  
Weige Lin ◽  
Linli Wang ◽  
Wenhan Zheng ◽  
...  
Keyword(s):  
3D Bioprinting ◽  
Uterine Endometrium ◽  
Human Ipsc

scholarly journals All-Optical Electrophysiology for High-Throughput Functional Characterization of a Human iPSC-Derived Motor Neuron Model of ALS

2018 ◽  
Vol 10 (6) ◽  
pp. 1991-2004 ◽  
Author(s):  
Evangelos Kiskinis ◽  
Joel M. Kralj ◽  
Peng Zou ◽  
Eli N. Weinstein ◽  
Hongkang Zhang ◽  
...  
Keyword(s):  
Motor Neuron ◽  
High Throughput ◽  
Neuron Model ◽  
Functional Characterization ◽  
All Optical ◽  
Human Ipsc

Selective Laser Foaming for Three-Dimensional Cell Culture on a Compact Disc

2015 ◽  
Author(s):  
JinGyu Ock ◽  
Wei Li
Keyword(s):  
Porous Structure ◽  
High Throughput ◽  
Drug Testing ◽  
3D Structure ◽  
Three Dimensional ◽  
Compact Disc ◽  
Laser Exposure ◽  
Porous Scaffolds ◽  
3D Scaffold ◽  
Tissue Model

A selective laser foaming process is developed to fabricate three-dimensional (3D) scaffold on a commercially available compact disc (CD) made of polycarbonate (PC). The laser-foamed 3D structure could be utilized to form high throughput perfusion-based tissue model device. In this study, effects of significant parameters and the morphology of porous structure were analyzed. As a result, laser foaming of gas saturated polycarbonate creates inverse cone-shaped wells with 3D porous structure on the surface region and the pores are tens of micrometers in diameter. The size of the well is dependent on the laser power and laser exposure time. The pore size relies on the gas concentration in the PC CD samples. The fabricated micro-scale porous scaffolds will be used to create centrifugal force driven two-chamber tissue model system arrays for high throughput drug testing.

On-chip hydrogel arrays individually encapsulating acoustic formed multicellular aggregates for high throughput drug testing

Lab on a Chip ◽  
2020 ◽  
Vol 20 (12) ◽  
pp. 2228-2236 ◽  
Author(s):  
Xuejia Hu ◽  
Shukun Zhao ◽  
Ziyi Luo ◽  
Yunfeng Zuo ◽  
Fang Wang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
High Throughput ◽  
Solid Tumor ◽  
Drug Testing ◽  
Three Dimensional ◽  
Multicellular Aggregates ◽  
3D Environments ◽  
On Chip ◽  
Insight Into

Multicellular aggregates in three-dimensional (3D) environments provide novel solid tumor models that can provide insight into in vivo drug resistance.

High-throughput generation of a concentration gradient on open arrays by serial and parallel dilution for drug testing and screening

2020 ◽  
Vol 305 ◽  
pp. 127487 ◽  
Author(s):  
Xinlian Chen ◽  
Bing Ji ◽  
Xinghua Gao ◽  
Mengying Zhang ◽  
Chang Xue ◽  
...  
Keyword(s):  
High Throughput ◽  
Concentration Gradient ◽  
Drug Testing

scholarly journals 3D bioprinting of mature bacterial biofilms for antimicrobial resistance drug testing

2019 ◽  
Vol 11 (4) ◽  
pp. 045018 ◽  
Author(s):  
Evita Ning ◽  
Gareth Turnbull ◽  
Jon Clarke ◽  
Fred Picard ◽  
Philip Riches ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Drug Testing ◽  
Bacterial Biofilms ◽  
3D Bioprinting

High-throughput assessment of compound-induced proarrhythmic effects in human iPSC-derived cardiomyocytes

2020 ◽  
Vol 105 ◽  
pp. 106742
Author(s):  
Oksana Sirenko ◽  
Carole Crittenden ◽  
Panida Lertkiatmongkol ◽  
April Guan ◽  
Borys Dresden ◽  
...  
Keyword(s):  
High Throughput ◽  
Human Ipsc

scholarly journals Phenotypic assays in yeast and zebrafish reveal drugs that rescue ATP13A2 deficiency

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Ursula Heins-Marroquin ◽  
Paul P Jung ◽  
Maria Lorena Cordero-Maldonado ◽  
Alexander D Crawford ◽  
Carole L Linster
Keyword(s):  
Heavy Metal ◽  
High Throughput ◽  
High Throughput Screening ◽  
Drug Testing ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Drug Repurposing ◽  
In Vivo Model ◽  
Inherited Disorders ◽  
Zebrafish Model

Abstract Mutations in ATP13A2 (PARK9) are causally linked to the rare neurodegenerative disorders Kufor-Rakeb syndrome, hereditary spastic paraplegia and neuronal ceroid lipofuscinosis. This suggests that ATP13A2, a lysosomal cation-transporting ATPase, plays a crucial role in neuronal cells. The heterogeneity of the clinical spectrum of ATP13A2-associated disorders is not yet well understood and currently, these diseases remain without effective treatment. Interestingly, ATP13A2 is widely conserved among eukaryotes, and the yeast model for ATP13A2 deficiency was the first to indicate a role in heavy metal homeostasis, which was later confirmed in human cells. In this study, we show that the deletion of YPK9 (the yeast orthologue of ATP13A2) in Saccharomyces cerevisiae leads to growth impairment in the presence of Zn2+, Mn2+, Co2+ and Ni2+, with the strongest phenotype being observed in the presence of zinc. Using the ypk9Δ mutant, we developed a high-throughput growth rescue screen based on the Zn2+ sensitivity phenotype. Screening of two libraries of Food and Drug Administration-approved drugs identified 11 compounds that rescued growth. Subsequently, we generated a zebrafish model for ATP13A2 deficiency and found that both partial and complete loss of atp13a2 function led to increased sensitivity to Mn2+. Based on this phenotype, we confirmed two of the drugs found in the yeast screen to also exert a rescue effect in zebrafish—N-acetylcysteine, a potent antioxidant, and furaltadone, a nitrofuran antibiotic. This study further supports that combining the high-throughput screening capacity of yeast with rapid in vivo drug testing in zebrafish can represent an efficient drug repurposing strategy in the context of rare inherited disorders involving conserved genes. This work also deepens the understanding of the role of ATP13A2 in heavy metal detoxification and provides a new in vivo model for investigating ATP13A2 deficiency.

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