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Bone Marrow Toxicity and Hematotoxicity Assays

Candidate drugs can be toxic to the sensitive cells of the bone marrow, primarily the blood-forming progenitor cells. Typical physiological consequences can be neutropenia and overall myelosuppression, and/or effects on other lineages including the erythroid (red blood cell progenitors) and megakaryocytic (platelet progenitor) lineages. Whether these effects are direct or indirect, they can be detected and evaluated using powerful functional in vitro Colony Forming Cell (CFC) or Colony Forming Unit (CFU) assays, using normal bone marrow cells from human, mice and other species.

One such CFC assay, the CFU-GM assay, has been found to be particularly valuable at predicting drug-induced neutropenia and myelosuppression and determining maximum tolerated dose (MTD). The CFU-GM assay has recently been validated by the European Commission for Alternative Methods (ECVAM), using multiple drug/chemical entities including immunosuppressive compounds, anti-neoplastics, anti-virals, and pesticides. Erythroid and megakaryotic effects can likewise be tested using CFC assays specific for those progenitors.

Please contact us to discuss your needs.

* ReachBio Study Directors are highly knowledgeable and have many years of experience in the science and practical aspects of bone marrow toxicity and hematotoxicity in both clinical and industrial settings.

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"Assays that predict the correct biomarker/histological changes drugs make and in vivo MTDs in humans at physiologically relevant exposures are exactly what we need. Bone marrow, liver, and lung assays are among the most important for anticancer therapeutics."

(NIH Roadmap ADMET Workshop, Bethesda, June 2004)