EXTRACELLULAR VESICLES FROM HUMAN IPS CELLS ENHANCE RECONSTITUTION CAPACITY OF CORD BLOOD-DERIVED HEMATOPOIETIC STEM AND PROGENITOR CELLS

Jun 29, 2022, 2:20 PM
10m
Room: S3 A

Room: S3 A

Speaker

Karnas, Elżbieta (Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University )

Description

Introduction: Human cord blood (CB) represents a rich source of several stem cell (SCs) types including hematopoietic stem and progenitor cells (HSPCs). Thus, clinical application of CB cells has become an alternative for the bone marrow transplantation. However, successful application of CB-HSPCs in adult patients requires the development of effective strategies improving their ex vivo expansion, homing and regenerative potential. One of the promising approaches for enhancement of SCs functionality includes their treatment with extracellular vesicles (EVs), which were shown to harbor and transfer bioactive content. Thus, in our study, for the first time we have evaluated an impact of human induced pluripotent SCs (hiPSCs)-derived EVs (hiPSC-EVs) on selected functions of CB-HSPCs, important for their hematopoietic potential in vitro and in vivo.

Methodology: hiPSC-EVs were harvested from media collected from feeder-, serum- and xeno- free cultures of hiPSCs by sequential ultracentrifugation. Next, CD45dimLin-CD34+ cell fraction enriched in HSPCs was isolated from CB by magnetic- (MACS) and fluorescence-activated cell sorting (FACS) and further expanded in dedicated serum- free media. Subsequently, we evaluated the influence of hiPSC-EVs on several biological and functional properties of CB-HSPCs in vitro and in vivo.

Results: Our results revealed that hiPSC-EVs may transfer their bioactive content and improve functional properties of CB-HSPCs including metabolic activity, hematopoietic and clonogenic potential, as well as survival, chemotactic response to stromal cell-derived factor 1 (SDF-1) and adhesion to the model components of hematopoietic niche in vitro. Importantly, hiPSC-EVs enhanced homing and engraftment of CB-HSPCs in vivo. Additionally, we have demonstrated that the treatment with hiPSC-EVs may activate signalling pathways in CB-HSPCs on both gene expression and the protein level.

Conclusion: In conclusion, our findings suggest that the “priming” with hiPSC-EVs may improve several functions of CB-HSPCs important for their homing and hematopoietic activity following the transplantation. These results support the new concept envisioning hiPSC-EVs as next-generation tools that may enhance future applications of CB in hematology.

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