Science and Research

Sensor macrophages derived from human induced pluripotent stem cells to assess pyrogenic contaminations in parenteral drugs

Ensuring the safety of parenteral drugs before injection into patients is of utmost importance. 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-

  • Abdin, S. M.
  • Mansel, F.
  • Hashtchin, A. R.
  • Ackermann, M.
  • Hansen, G.
  • Becker, B.
  • Kick, B.
  • Pham, N.
  • Dietz, H.
  • Schaniel, C.
  • Martin, U.
  • Spreitzer, I.
  • Lachmann, N.

Keywords

  • *Induced Pluripotent Stem Cells/cytology/metabolism
  • Humans
  • *Macrophages/metabolism/drug effects/cytology
  • *Pyrogens
  • Drug Contamination
  • Toll-Like Receptors/metabolism
  • Endotoxins
  • Interleukin-6/metabolism
  • Monocytes/cytology/metabolism/drug effects
  • Infusions, Parenteral
  • Mat
  • endotoxin
  • iPSC
  • macrophages
  • non-endotoxin
  • pharmacopeia
  • pyrogens
Publication details
DOI: 10.1088/1758-5090/ad4744
Journal: Biofabrication
Number: 3
Work Type: Original
Location: BREATH
Disease Area: General Lung and Other
Partner / Member: ITEM, MHH
Access-Number: 38701770

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