HeMOToX:A non-animal new approach methodology to test predict human blood toxicity like safety concerns
The hematopoietic system, like most biological systems in the body, is a stem cell system. The hematopoietic system is unique, however, in that it has the potential to produce multiple cell types, each with different functions, from a single stem cell. For all biological systems, the stem cell, or rather the stem cell compartment, which contains many different stages of stem cell primitiveness or maturity, is the foundation upon which all biological systems are built.
Damage to the stem cell compartment, or any part of it, can mean damage to the biological system and the organism as a whole. Stem cell hematotoxicity refers to damage to the stem cell compartment that affects the rest of the lympho-hematopoietic system, its organization, regulation and feedback mechanisms that are required to maintain a steady state condition.
Bone marrow toxicity, which is often referred to as myelotoxicity, means toxicological damage to one or more parts of the lympho-hematopoietic systems and microenvironmental system that supports it.
From the viewpoint of toxicology, hematotoxicity and immunotoxicity are inseparable, since common stem cells give rise to both systems and, if these are damaged, both systems will be affected. It is for this reason why detecting the response of stem cells to potentially toxic agents can provide predictive information for the rest of the lympho-hematopoietic system.
Conventional pathology to detect toxicity to the bone marrow and other hematopoietic tissues during pre-clinical animal testing does not provide the predictive insight of advanced in vitro toxicity testing platforms like that of HeMOToX.
During the late 1990s and early 2000s, the European Center for the Validation of Alternative Methods (ECVAM) published several articles on using the colony-forming cell (CFC) assay to predict drug-induced myelosuppression. The studies were initially focused on the myelomonocytic (granulocyte-macrophage) lineage and later the megakaryocytic lineage.
Avila AM, Bebenek I, Bonzo JA, Bourcier T, Davis Bruno KL, Carlson DB, Dubinion J, Elayan I, Harrouk W, Lee SL, Mendrick DL, Merrill JC, Peretz J, Place E, Saulnier M, Wange RL, Yao J, Zhao D, Brown PC. An FDA/CDER perspective on nonclinical testing strategies: Classical toxicology approaches and new approach methodologies (NAMs). Regul Toxicol Pharmacol. 2020 Jul;114:104662. doi: 10.1016/j.yrtph.2020.104662. Epub 2020 Apr 20. PMID: 32325112.