An In Vitro Model of Hematotoxicity: Differentiation of Bone Marrow–Derived Stem/Progenitor Cells into Hematopoietic Lineages and Evaluation of Lineage‐Specific Hematotoxicity. Issue 1 (30th April 2018)

• Record Type: Journal Article
• Authors: Mahalingaiah, Prathap Kumar; Palenski, Tammy; Van Vleet, Terry R.
• Editors: Bus, James S.; Costa, Lucio G.; Hodgson, Ernest; Lawrence, David A.; Reed, Donald J.
• Is Part Of: Current protocols in toxicology. Volume 76:Issue 1(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-04-30
• Subjects: CD34+ cells -- hematopoietic stem/progenitor cells -- hematotoxicity -- in vitro model; Toxicology -- Laboratory manuals; Toxicology -- methods; Toxicology; Laboratory Manual; Electronic books; Laboratory manuals; 571.95028
• DOI: 10.1002/cptx.45
• Languages: English
• ISSNs: 1934-9254

Abstract

Abstract: Hematotoxicity is a significant issue for drug safety and can result from direct cytotoxicity toward circulating mature blood cell types as well as targeting of immature blood‐forming stem cells/progenitor cells in the bone marrow. In vitro models for understanding and investigating the hematotoxicity potential of new test items/drugs are critical in early preclinical drug development. The traditional method, colony forming unit (CFU) assay, is commonly used and has been validated as a method for hematotoxicity screening. The CFU assay has multiple limitations for its application in investigative work. In this paper, we describe a detailed protocol for a liquid‐culture, microplate‐based in vitro hematotoxicity assay to evaluate lineage‐specific (myeloid, erythroid, and megakaryocytic) hematotoxicity at different stages of differentiation. This assay has multiple advantages over the traditional CFU assay, including being suitable for high‐throughput screening and flexible enough to allow inclusion of additional endpoints for mechanistic studies. Therefore, it is an extremely useful tool for scientists in pharmaceutical discovery and development. © 2018 by John Wiley & Sons, Inc.