Compound Screening Service using iPSC-derived Cells

Axcelead DDP and FUJIFILM Cellular Dynamics Inc. support your drug discovery using iCell® Products

iPSC-derived cell types are useful physiologically relevant models of human diseases.
Recently, compounds discovered in phenotypic screening using iPSC-derived cells have been shown to be effective in clinical trials, thus making the use of iPSC-derived cells for drug screening an attractive approach.

Axcelead DDP supports your drug discovery using iPSC-derived cells from assay development through high-throughput screening using iPSC-derived cells from FUJIFILM Cellular Dynamics Inc. (FCDI),a leading company of iPSC technologies. 

Axcelead DDP Phenotypic Screening Services

We support your Phenotypic Drug Discovery using iCell Products by utilizing the scientific experiences of Axcelead DDP and FUJIFILM Cellular Dynamics, Inc.

*For more information about the various iCell Products from FUJIFILM Cellular Dynamics available for Screening Services, visit here

Our capabilities support you throughout your screening process:

For example, you can use this service in the following situations!

A Variety of Assays and Experiences in Phenotypic Screening

Case study

Screening for Phagocytosis Modulators using iCell® Microglia AD TREM2

Goal
To discover phagocytosis activators using iCell® Microglia AD TREM2 homozygous knockout (iCell Microglia TREM2 HO)cells.

Background
Mutations in the transmembrane protein, TREM2, has become a research focus because of its role in the binding and clearance of Aβ oligomers, thus making it a potential risk factor of Alzheimer’s disease. Elucidation of the mechanism would be useful for development of therapies for Alzheimer’s disease. 

Assay Development
A biologically annotated compound library, consisting of about 3,400 compounds, was tested in a phagocytosis assay using iCell Microglia TREM2 HO to screen for phagocytosis activators.
Compound concentration for the primary screening was set at 3 µM. 


Assay Development Results
We optimized an assay to evaluate cellular uptake activity of fluorescent-labeled Aβ in a 384-well format using InCuCyte® ZOOM. Results showed Aβ uptake kinetics in iCell Microglia TREM2 HO was slower than that of iCell Microglia (wild type, WT).


Screening Cascade Outline


Primary Screen Results
After the primary screening step, false-positive compounds (e.g., auto-fluorescence, cell toxic, and others) were removed. Based on the activity distribution from the primary screening, positive compounds were selected for a following screening cascade, reproducibility assay and concentration-response assay.

Correlation between Aβ uptake activity and cytotoxicity in the primary screening


Correlation between Aβ uptake activity and cytotoxicity in the primary screening


Dose Response Results
We successfully identified several phagocytosis activators. These compounds enhanced phagocytosis activity without severe cytotoxicity.
Representative compounds, A and B, increased the phagocytosis activity in iCell Microglia TREM2 HO comparable to levels of iCell Microglia. Compound A enhanced phagocytosis activity in both iCell Microglia and iCell Microglia TREM2 HO, while compound B increased it only in iCell Microglia TREM2 HO, suggesting that these compounds modulated phagocytosis activity through different mode-of–actions.

Axcelead DDP Phenotypic Screening Services

Our vast experience in phenotypic screening combined with our diverse compound libraries provides high-quality phenotypic screening services. 

High-throughput screening capability for Phenotypic drug discovery

Related Services

navigate_next Target Deconvolution