Phthalates affect the in vitro expansion of human hematopoietic stem cell

Phthalates are esters of phthalic acid used industrially as plastic additives, however, these are not covalently bound to the polymer matrix and therefore can be released to the environment. The aim of this study was to evaluate the effect of four phthalates: dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), diethyl phthalate (DEP) and diethylhexyl phthalate (DEHP) on the in vitro expansion of human hematopoietic cells from umbilical cord blood. For this, 0.5 × 10⁶ cells/mL were exposure to concentrations ranging from 0.1 to 100 μg/mL and the total cell expansion was determined after 14 days of culture in IMDM-cytokines medium. The control cultures attained 1.31 ± 0.21 × 10⁶ cell/mL, whereas the cultures exposed to DBP, BBP and DEHP showed a reduction from 23 to 81%, 17 to 69% and 15 to 93.5%, respectively. DEP did not affect the total cell expansion. The most significant decrease on total cell expansion was observed at 0.1 μg/mL DBP, 100 μg/mL BBP and 10 μg/mL DEHP (p < 0.05). Additionally, the effect of these compounds on the expansion of hematopoietic progenitors was analyzed by clonogenic assays as colony forming units (CFU). The CFU decreased considerably compared with respect to the control cultures. The reduction was 74.6 and 99.1% at 10 and 100 μg/mL DBP respectively, whereas 100 μg/mL BBP and 100 μg/mL DEHP reduced the CFU expansion in 97.1% and 81%, respectively. Cultures exposed to DEP did not show significant differences. The results demonstrate the toxicity of DBP, BBP and DEHP on the human hematopoietic stem cells.