Toxicity of poly-dispersed single-walled carbon nanotubes on bone marrow derived Hematopoietic Stem and Progenitor Cells

Curr Res Toxicol. 2021 Feb 20:2:82-92. doi: 10.1016/j.crtox.2021.02.003. eCollection 2021.

Abstract

This study has explored the effect of acid-functionalized single-walled carbon nanotubes (AF-SWCNTs) on Hematopoietic Stem and Progenitor Cell (HSPCs) in mouse bone marrow. Administration of AF-SWCNTs induced a significant decline in the live-cell recovery from bone marrow. Lin-negative Stem cell enriched HSPCs internalized AF-SWCNTs that remained localized in cytoplasmic areas. Incubation of HSPCs with AF-SWCNTs resulted in induction of cell death, inhibition of cell cycle, and induction of reactive oxygen species (ROS) as well as the expression of Caspase 3, 7 and 9 enzymes. In vitro culture with a cytokine cocktail (SCF, GM-CSF, IL3, IL6, IL7) induced differentiation of HSPCs into lymphocytes and myeloid cells, that was inhibited in presence of AF-SWCNTs. Relative recoveries of lymphocytes specifically B lymphocytes, was significantly reduced by AF-SWCNT-treatment, whereas the relative recovery of myeloid cells remained unaltered. These results suggest that AF-SWCNTs have significant toxic effects on HSPCs and differentially suppress the ontogeny of lymphoid and myeloid cells.

Keywords: AF-SWCNTs, Acid-functionalized single-walled carbon nanotubes; CNTs, Carbon Nanotubes; Carbon nanotubes; Caspase; FAF-SWCNTs, Fluorescence tagged AF-SWCNTs; HSC, Hematopoietic stem cells; HSPC(dp), SCA-1+ cKit+ cell population within HSPCs; HSPCs, Lineage negative stem cell-enriched cells obtained after negative selection of bone marrow cells; Hematopoietic stem cells; Lymphoid and myeloid differentiation; ROS; ROS, Reactive Oxygen Species.