The DivisionCounter, a method for counting large ranges of cell divisionsin vivo,reveals cell dynamics of leukemic cell killing via CAR-T therapy

Abstract

AbstractCell division drives multicellular growth and its dysregulation can cause disease. While approximately 44 divisions are needed to produce without death all 1013cells in the human body, current methods are limited to count 10 cell divisionsin vivoacross diverse mammalian cell types. Here we introduce the DivisionCounter, a method to count cell divisionin vivoover large division ranges (∼70 divisions) using an easy fluorescence readout. We demonstrate that the DivisionCounter accurately measures the average cell division count of cells bothin vitroandin vivo. Its use revealed that leukemia tumor division rates are independent of the organ’s specific microenvironment and CAR-T cell treatment, providing an estimate of tumor death ratesin vivo. The DivisionCounter method holds unique potential for quantifying contributions of cell division, death, and migration to the growth of healthy and pathological mammalian tissues.