Abstract
In vitro clonogenic assays have been developed and widely used since many years to investigate the proliferation and the differentiation both of pluripotent haemopoietic stem cells (PHSC) and of the different progenitors of blood cell lineages: megakaryocytes (Colony Forming Unit-Mk) granulocyte -macrophage (CFU-GM), erythrocytes (BFU-E/CFU-E). As these techniques have been introduced, they appeared to be very useful to investigate the pathogenic mechanisms of drug induced blood disorders and also for screening compound during preclinical safety study. Because the integrity of the hematopoiesis is also essential to guarantee the immunological function, the application to the toxicology of these clonogenic assays, provides an essential tool for better understanding the in vivo observation (experimental and clinical) by also helping in predicting the degree of a possible in vivo hematotoxic in drug treated patients. The review introduces to basic concepts on hematopoiesis and on classical evaluation of a drug hematotoxic phenomenon. It describes the application of each clonogenic test to assess the specific hematotoxicity action. Moreover it report the most recent studies on standardisation, prevalidation and validation of such assays and critically reviews a model for predicting myelotoxicity by discussing the main aspects referred to the evaluation of the in vivo acute neutropenia by using the in vitro CFU-GM assay.
Keywords: clonogenic assay, hematotoxicity, myelotoxicity, bfu-e/cfu-e, cfu-gm, cfu-mk prediction model validation
Current Pharmaceutical Design
Title: Hematotoxicity Testing by Cell Clonogenic Assay in Drug Development and Preclinical Trials
Volume: 11 Issue: 8
Author(s): Augusto Pessina, Ilaria Malerba and Laura Gribaldo
Affiliation:
Keywords: clonogenic assay, hematotoxicity, myelotoxicity, bfu-e/cfu-e, cfu-gm, cfu-mk prediction model validation
Abstract: In vitro clonogenic assays have been developed and widely used since many years to investigate the proliferation and the differentiation both of pluripotent haemopoietic stem cells (PHSC) and of the different progenitors of blood cell lineages: megakaryocytes (Colony Forming Unit-Mk) granulocyte -macrophage (CFU-GM), erythrocytes (BFU-E/CFU-E). As these techniques have been introduced, they appeared to be very useful to investigate the pathogenic mechanisms of drug induced blood disorders and also for screening compound during preclinical safety study. Because the integrity of the hematopoiesis is also essential to guarantee the immunological function, the application to the toxicology of these clonogenic assays, provides an essential tool for better understanding the in vivo observation (experimental and clinical) by also helping in predicting the degree of a possible in vivo hematotoxic in drug treated patients. The review introduces to basic concepts on hematopoiesis and on classical evaluation of a drug hematotoxic phenomenon. It describes the application of each clonogenic test to assess the specific hematotoxicity action. Moreover it report the most recent studies on standardisation, prevalidation and validation of such assays and critically reviews a model for predicting myelotoxicity by discussing the main aspects referred to the evaluation of the in vivo acute neutropenia by using the in vitro CFU-GM assay.
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Cite this article as:
Pessina Augusto, Malerba Ilaria and Gribaldo Laura, Hematotoxicity Testing by Cell Clonogenic Assay in Drug Development and Preclinical Trials, Current Pharmaceutical Design 2005; 11 (8) . https://dx.doi.org/10.2174/1381612053381648
DOI https://dx.doi.org/10.2174/1381612053381648 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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