Methods for advanced hepatocyte cell culture in microwells utilizing air bubbles

Lab on a Chip ◽  
2015 ◽  
Vol 15 (4) ◽  
pp. 1032-1037 ◽  
Author(s):  
Vasiliy N. Goral ◽  
Sam H. Au ◽  
Ronald A. Faris ◽  
Po Ki Yuen
Keyword(s):  
Cell Culture ◽  
High Throughput ◽  
Drug Screening ◽  
Specific Cell ◽  
Air Bubbles ◽  
Cytotoxicity Assays ◽  
High Throughput Drug Screening ◽  
Cellular Microenvironments ◽  
Substantial Control

We present a number of novel and unique methods for advanced cell culture in microwells utilizing air bubbles to provide substantial control over cellular microenvironments and organization in order to achieve specific cell-based applications, and an easy way for high throughput drug screening and cytotoxicity assays.

Development of a novel multi-layer microfluidic device towards characterization of drug metabolism and cytotoxicity for drug screening

2014 ◽  
Vol 50 (21) ◽  
pp. 2762-2764 ◽  
Author(s):  
Qin Wu ◽  
Dan Gao ◽  
Juntong Wei ◽  
Feng Jin ◽  
Weiyi Xie ◽  
...  
Keyword(s):  
Drug Metabolism ◽  
Microfluidic Device ◽  
High Throughput ◽  
Drug Screening ◽  
Cytotoxicity Assays ◽  
High Throughput Drug Screening

A multi-layer microfluidic device was developed for characterization of drug metabolism and cytotoxicity assays on a single device that overcomes many limitations of existing methods. And it also shows potential for high-throughput drug screening.

High-Throughput Drug Screening of FDA-Approved Cancer Drugs Reveals Novel Therapies for Patients with Chordomas

2019 ◽  
Author(s):  
Philip Tatman ◽  
Anthony Fringuello ◽  
Denise Damek ◽  
Samy Youssef ◽  
Randy Jensn ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Screening ◽  
Novel Therapies ◽  
Cancer Drugs ◽  
High Throughput Drug Screening

High-Throughput Drug Screening of ECM Deposition Inhibitors for Antifibrotic Drug Discovery

2019 ◽  
Author(s):  
Michael Gerckens ◽  
Hani Alsafadi ◽  
Darcy Wagner ◽  
Katharina Heinzelmann ◽  
Kenji Schorpp ◽  
...  
Keyword(s):  
Drug Discovery ◽  
High Throughput ◽  
Drug Screening ◽  
High Throughput Drug Screening

Therapeutic stratification of acute leukemia using high throughput drug screening

2020 ◽  
Author(s):  
S Bhatia ◽  
H Ahlert ◽  
N Dienstbier ◽  
J Schliehe-Diecks ◽  
M Sönnichsen ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
High Throughput ◽  
Drug Screening ◽  
High Throughput Drug Screening

scholarly journals High-throughput drug screening identifies the ATR-CHK1 pathway as a therapeutic vulnerability of CALR mutated hematopoietic cells

2021 ◽  
Vol 11 (7) ◽  
Author(s):  
Ruochen Jia ◽  
Leon Kutzner ◽  
Anna Koren ◽  
Kathrin Runggatscher ◽  
Peter Májek ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Screening ◽  
Synthetic Lethality ◽  
Myeloproliferative Neoplasms ◽  
Hematopoietic Cells ◽  
Replication Stress ◽  
Phase Cell ◽  
Nuclear Staining ◽  
Wild Type ◽  
High Throughput Drug Screening

AbstractMutations of calreticulin (CALR) are the second most prevalent driver mutations in essential thrombocythemia and primary myelofibrosis. To identify potential targeted therapies for CALR mutated myeloproliferative neoplasms, we searched for small molecules that selectively inhibit the growth of CALR mutated cells using high-throughput drug screening. We investigated 89 172 compounds using isogenic cell lines carrying CALR mutations and identified synthetic lethality with compounds targeting the ATR-CHK1 pathway. The selective inhibitory effect of these compounds was validated in a co-culture assay of CALR mutated and wild-type cells. Of the tested compounds, CHK1 inhibitors potently depleted CALR mutated cells, allowing wild-type cell dominance in the co-culture over time. Neither CALR deficient cells nor JAK2V617F mutated cells showed hypersensitivity to ATR-CHK1 inhibition, thus suggesting specificity for the oncogenic activation by the mutant CALR. CHK1 inhibitors induced replication stress in CALR mutated cells revealed by elevated pan-nuclear staining for γH2AX and hyperphosphorylation of RPA2. This was accompanied by S-phase cell cycle arrest due to incomplete DNA replication. Transcriptomic and phosphoproteomic analyses revealed a replication stress signature caused by oncogenic CALR, suggesting an intrinsic vulnerability to CHK1 perturbation. This study reveals the ATR-CHK1 pathway as a potential therapeutic target in CALR mutated hematopoietic cells.

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