Enhancement of monocytopoiesis and erythropoiesis in human bone marrow-derived hematopoietic stem cells by placental extracellular vesicles.

INTRODUCTION

Maternal blood composition undergoes profound changes during pregnancy to meet immunological, hemostatic, and oxygen demands. Despite the importance of these adaptations, the mechanisms regulating maternal hematopoiesis remain poorly understood. An interaction between maternal hematopoietic stem cells (HSCs) and placenta-derived extracellular vesicles (EVs) may play a key role in this process.

METHODS

Primary human bone marrow-derived CD34+ HSCs were cultured for seven days in the presence of placenta-derived EVs. EVs were isolated from 3-h ex vivo human placenta perfusions followed by serial ultracentrifugations. EV quality and integrity were assessed by Western blotting for characteristic markers, nanoparticle tracking analysis for size distribution, and transmission electron microscopy. HSC capture of fluorescence-labelled EVs was confirmed by flow cytometry. HSC differentiation was monitored by flow cytometric analysis of lineage-specific surface markers.

RESULTS

Specific EV subpopulations were successfully enriched. During the 4-h culture period, hematopoietic stem cells (HSCs) internalized significantly more small extracellular vesicles (sEVs) than large extracellular vesicles (lEVs). After 7 days of incubation, both sEVs and lEVs promoted enhanced differentiation of HSCs into CD235a+ erythroid cells and CD14+ monocytes compared with untreated controls.

CONCLUSION

The findings indicate that fetal EVs released into the maternal circulation can modulate maternal hematopoiesis, particularly enhancing erythropoiesis and monocytopoiesis.