دورية أكاديمية
Application of human iPSC-derived macrophages in a miniaturized high-content-imaging-based efferocytosis assay
| العنوان: | Application of human iPSC-derived macrophages in a miniaturized high-content-imaging-based efferocytosis assay |
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| المؤلفون: | Sarah Bitzer, Mozhgan Dehghan Harati, Karim C. El Kasmi, Daniela Schloesser, Julia Sauer, Heiko Olbrich, Michael Schuler, Florian Gantner, Ralf Heilker |
| المصدر: | SLAS Discovery, Vol 28, Iss 4, Pp 149-162 (2023) |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2023 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | hiPSC-derived macrophages, Upscaling, High-content-imaging, Miniaturization, Efferocytosis, Medicine (General), R5-920, Biotechnology, TP248.13-248.65 |
| الوصف: | Macrophages play a pivotal role in drug discovery due to their key regulatory functions in health and disease. Overcoming the limited availability and donor variability of human monocyte-derived macrophages (MDMs), human induced pluripotent stem cell (iPSC)-derived macrophages (IDMs) could provide a promising tool for both disease modeling and drug discovery. To access large numbers of model cells for medium- to high-throughput application purposes, an upscaled protocol was established for differentiation of iPSCs into progenitor cells and subsequent maturation into functional macrophages. These IDM cells resembled MDMs both with respect to surface marker expression and phago- as well as efferocytotic function. A statistically robust high-content-imaging assay was developed to quantify the efferocytosis rate of IDMs and MDMs allowing for measurements both in the 384- and 1536-well microplate format. Validating the applicability of the assay, inhibitors of spleen tyrosine kinase (Syk) were shown to modulate efferocytosis in IDMs and MDMs with comparable pharmacology. The miniaturized cellular assay with the upscaled provision of macrophages opens new routes to pharmaceutical drug discovery in the context of efferocytosis-modulating substances. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2472-5552 |
| العلاقة: | http://www.sciencedirect.com/science/article/pii/S2472555223000308Test; https://doaj.org/toc/2472-5552Test; https://doaj.org/article/682b49992ecd4d21b4b00356826270d2Test |
| DOI: | 10.1016/j.slasd.2023.04.002 |
| الإتاحة: | https://doi.org/10.1016/j.slasd.2023.04.002Test https://doaj.org/article/682b49992ecd4d21b4b00356826270d2Test |
| رقم الانضمام: | edsbas.476BABDC |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 24725552 |
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| DOI: | 10.1016/j.slasd.2023.04.002 |