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New regulations around the globe and the need to refrain from using animals however, have highlighted the need for new cell sources to be used in next-generation bioassays to detect the entire spectrum of possible contaminating pyrogens. Given the current drawbacks of the Monocyte-Activation-Test (MAT) with respect to the use of primary peripheral blood mono-nuclear cells or the use of monocytic cell lines, we here demonstrate the manufacturing of sensor monocytes\/macrophages from human induced pluripotent stem cells (iMonoMac), which are fully defined and superior to current cell products. Using a modern and scalable manufacturing platform, iMonoMac showed typical macrophage-like morphology and stained positive for several Toll like receptor (TLRs) such as TLR-2, TLR-5, TLR-4. Furthermore, iMonoMac derived from the same donor were sensitive to endotoxins, non-endotoxins, and process related pyrogens at a high dynamic range and across different cellular densities. Of note, iMonoMac showed increased sensitivity and reactivity to a broad range of pyrogens, demonstrated by the detection of interleukin-6 at low concentrations of LPS and MALP-2 which could not be reached using the current MAT cell sources. To further advance the system, iMonoMac or genetically engineered iMonoMac with NF-<jats:italic>\u03ba<\/jats:italic>B-luciferase reporter cassette could reveal a specific activation response while correlating to the classical detection method employing enzyme-linked immunosorbent assay to measure cytokine secretion. Thus, we present a valuable cellular tool to assess parenteral drugs safety, facilitating the future acceptance and design of regulatory-approved bioassays.<\/jats:p>","DOI":"10.1088\/1758-5090\/ad4744","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T22:29:11Z","timestamp":1714775351000},"page":"035017","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Sensor macrophages derived from human induced pluripotent stem cells to assess pyrogenic contaminations in parenteral drugs"],"prefix":"10.1088","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2534-5726","authenticated-orcid":true,"given":"Shifaa M","family":"Abdin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederike","family":"Mansel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Rafiei","family":"Hashtchin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mania","family":"Ackermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gesine","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Kick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nhi","family":"Pham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Dietz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schaniel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Spreitzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico","family":"Lachmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2024,5,17]]},"reference":[{"key":"bfad4744bib1","doi-asserted-by":"publisher","first-page":"119","DOI":"10.5692\/clinicalneurol.cn-001235","article-title":"Cell therapy for Parkinson\u2019s disease with induced pluripotent stem cells","volume":"59","author":"Morizane","year":"2019","journal-title":"Rinsho Shinkeigaku"},{"key":"bfad4744bib2","doi-asserted-by":"publisher","first-page":"269","DOI":"10.3390\/cells11020269","article-title":"Advances in allogeneic cancer cell therapy and future perspectives on \u201cOff-the-Shelf\u201d T cell therapy using iPSC technology and gene editing","volume":"11","author":"Furukawa","year":"2022","journal-title":"Cells"},{"key":"bfad4744bib3","doi-asserted-by":"publisher","DOI":"10.1038\/srep19111","article-title":"Enhanced engraftment, proliferation, and therapeutic potential in heart using optimized human iPSC-derived cardiomyocytes","volume":"6","author":"Funakoshi","year":"2016","journal-title":"Sci. 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