Publication date: May 27, 2025
New treatments are still necessary to eradicate tuberculosis disease. Macrophages derived from human induced pluripotent stem cells (hiPSC-Macs) offer a physiological niche to identify potential new drugs in the context of Mycobacterium tuberculosis (Mtb) infection. Here, we describe the scale-up of hiPSC-Macs production in 5-stack chambers for high-throughput drug screening against Mtb. A rate of approximately 100 million hiPSC-Macs was generated with optimal quality for a period of up to 12 weeks. Moreover, the infection model was optimized using a luminescence-based Mtb reporter strain. The assay showed enough sensitivity to identify compounds that could target host-pathogen interactions during Mtb infection. We interrogated a library of 200,000 compounds in Mtb-infected hiPSC-Macs with a Z-score above 0. 3 in all plates analyzed. After secondary assays, 223 qualified hits were selected for further progression.
| Concepts | Keywords |
|---|---|
| Drugs | drug screening |
| High | host-pathogen interactions |
| Library | macrophages |
| Macs | tuberculosis |
| Mycobacterium |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | tuberculosis |
| pathway | KEGG | Tuberculosis |
| disease | MESH | infection |
| disease | IDO | production |
| disease | IDO | quality |
| disease | IDO | assay |
| disease | IDO | host |
| disease | IDO | pathogen |