Citation:

Das, K., C. Lau, AND K. Dreher. Effect of Environmental Chemical Exposures on Adult Human Cardiac Progenitor Cell Viability and Differentiation. 2017 SOT Annual meeting, Baltimore, Maryland, March 12 - 16, 2017.

Impact/Purpose:

Results indicate that: i) a variety of environmental chemicals, at low in vitro concentrations, can impact adult human CPCs in several ways including decreased viability and\or differentiation to CMs; ii) there may exist species and\or developmental differences between current models that assess the impact of environmental chemicals on CSC or CPC viability or CM differentiation potential.

Description:

Cell biology has revealed that the adult heart is not a terminally differentiated organ but is capable of generating new cardiomyocytes (CMs) from cardiac stem cells (CSC) and/or progenitor cells (CPC) throughout life. The impact that environmental chemical exposures have on adult human CPCs, and therefore the adult heart’s cellular generative potential, is unknown. To address this uncertainty a scalable assay using adult human inducible pluripotent stem cell-derived CPCs is being developed to determine the effects of various environmental chemicals on their viability and differentiation. CPC cytotoxicity and differentiation were determined by quantitative fluorescent analysis (LI-COR Odyssey CLx Imaging System) using Red Dot1 nuclear and anti-cardiac troponin T antibody in-cell western staining, respectively. Optimal induction of CPCs into CMs was obtained by treatment with both Wnt (10 µM XAV939) and activin/TGFβ (2.5 µM SB431542) inhibitors for 48h (5 - 10% cardiac troponin T+ with no treatment vs. 50 – 60% cardiac troponin T+ with inducers). CPCs were exposed to vehicle controls or triclosan, bisphenol A, CeCl3 each at 0.125 to 12.5 µM or a saline extract of residual oil fly ash (ROFA-L) at 0.02 to 20 µg/ml concentrations in the presence of CPC differentiation inducers for 48h. CPC cultures were stained with Red Dot1 and anti-cardiac troponin T at 6 days post-exposure. Exposure to vehicle (saline or dimethyl sulfoxide) did not affect viability or differentiation of CPCs to CMs. Exposure of CPCs to CeCl3 produced a dose dependent decrease in their ability to differentiate into CMs with no effect on cytotoxicity. In contrast to a previous study with murine stem cells, exposure of adult human CPCs to triclosan, or ROFA-L, led to a dose dependent increase in CPC cytotoxicity. Bisphenol A had no effect on human CPC cytotoxicity or differentiation to CMs. These results indicate that a variety of environmental chemicals, at low in vitro concentrations, can impact adult human CPCs in several ways including decreased viability and\or differentiation to CMs. In addition, there may exist species and\or developmental differences between current models that assess the impact of environmental chemicals on CSC or CPC viability or CM differentiation potential. (This abstract does not represent EPA policy)

Record Details: