title: Age-structured population model of cell survival.
abstract: Age-structured cell population model was introduced to describe cell survival. The impact of the environment on the cell population is represented by drug plasma concentration. A key model variable is the hazard of cell removal that is a subject to the environment effect. The model is capable of describing cohort and random labeling cell survival data. In addition, it accounts for cell loss due to labeling of cell sample, but it lacks ability to describe the effect of label elution on the survival data. The model was applied to red blood cell (RBC) survival data in two groups of Wistar rats obtained by two techniques: cohort labeling using14C-glycine (N = 4) and random labeling using biotin (N = 8). The Weibull probability density function was selected for the RBC lifespan distribution. The data were simultaneously fitted by the mixed effects model implemented in Monolix 4.3.3. The estimated typical values of RBC lifespan and age were 53.7 and 27.8 days, respectively. A noticeable effect of biotinylation on RBC survival was observed that resulted in a significant difference between the means of individual RBC lifespan for two groups. The model provides a mechanistic framework flexible enough to account for various experimental designs to generate the cell survival data. Despite model qualification using animal data, the model has the same potential to be applied to cell survival data analysis in humans.
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, 370 Kapoor Hall, Buffalo, NY, 14214, USA. wk@buffalo.edu.
authors.forename: Wojciech
authors.identifier: 0000-0001-9773-1739
authors.initials: W
authors.lastname: Krzyzanski
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, 370 Kapoor Hall, Buffalo, NY, 14214, USA.|Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Gdańsk, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Wiczling
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, 370 Kapoor Hall, Buffalo, NY, 14214, USA.|Department of Clinical Pharmacology and Biomarkers, Vertex Pharmaceuticals Inc, Boston, MA, USA.
authors.forename: Asfiha
authors.initials: A
authors.lastname: Gebre
mesh_terms: D000818:Animals; D001710:Biotin / Q000032:analysis; D002470:Cell Survival / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology*; D004912:Erythrocytes / Q000737:chemistry / Q000502:physiology*; D008297:Male; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling / Q000379:methods
chemical_list: D001710:Biotin
keywords: Age-structured population; Cell survival; Cohort labeling; Death hazard; Lifespan; Random labeling; Weibull function