Development of an In vitro Cultivated, Spontaneously and Long-term Contracting 3D Heart Model as a Robust Test System

Abstract

Background: Beside its anti-proliferative, anti-hypertensive and anti-inflammatory effects, heparin has shown the apoptotic effect in lymphoblasts. In the study, it is aimed to show the apoptotic effect of heparin in lymphoblasts with measuring intracellular calcium and using DNA analysis by flow cytometry, in vitro. Methods: Twenty-three newly diagnosed acute lymphoblastic leukemia patients were included in the study. We added 10 and 20 U/ml heparin into the seperated lymphoblast samples and determined the percentages of apoptosis and intracellular Ca++ levels at 0, 1 and 2 hours by flow cytometry, in vitro. Results: The apoptotic effect on the lymphoblasts were established in 10 and 20 U/ml heparin concentrations at 0, 1 and 2 hours (p=0.005). The apoptotic effect of heparin in lymphoblasts was higher at the first hour than those at 0 and 2 hours in 10 and 20 U/ml heparin concentrations (p=0.005). The highest apoptosis was determined in 20 U/ml heparin concentration at the first hour. Statistically significant increase in intracellular Ca++ levels were determined in 10 and 20 U/ml heparin concentrations at 1 and 2 hours (p=0.005). In 10 and 20 U/ml heparin concentrations, intracellular Ca++ levels were significantly higher at the first hour than 0 and 2 hours (p=0.005). The highest intracellular Ca++ concentration was determined in 20 U/ml heparin concentration at the first hour. Conclusion: Heparin induces apoptosis in lymphoblasts and intracellular Ca++ levels of the lymphoblasts synchronously increase with apoptosis. The increase of intracellular Ca++ level supports a concept that the mitochondria plays a role heparin-induced apoptosis in lymphoblasts.