Abstract
Cord blood (CB) represents a source of hematopoietic stem and progenitor cells (CB-HSPCs) for bone marrow (BM) reconstitution, but clinical CB application is limited in adult patients due to the insufficient number of CB-HSCPCs and the lack of effective ex vivo approaches to increase CB-HSPC functionality. Since human-induced pluripotent stem cells (hiPSCs) have been indicated as donor cells for bioactive extracellular vesicles (EVs) modulating properties of other cells, we are the first to employ hiPSC-derived EVs (hiPSC-EVs) to enhance the hematopoietic potential of CB-derived CD45dimLin-CD34+ cell fraction enriched in CB-HSPCs. We demonstrated that hiPSC-EVs improved functional properties of CB-HSPCs critical for their hematopoietic capacity including metabolic, hematopoietic and clonogenic potential as well as survival, chemotactic response to stromal cell-derived factor 1 and adhesion to the model components of hematopoietic niche in vitro. Moreover, hiPSC-EVs enhanced homing and engraftment of CB-HSPCs in vivo. This phenomenon might be related to activation of signaling pathways in CB-HSPCs following hiPSC-EV treatment, as shown on both gene expression and the protein kinases activity levels. In conclusion, hiPSC-EVs might be used as ex vivo modulators of CB-HSPCs capacity to enhance their functional properties and augment future practical applications of CB-derived cells in BM reconstitution.
Highlights
Human umbilical cord blood (CB) is a rich source of various stem and progenitor cell types, including non-hematopoietic and hematopoietic stem and progenitor cells (HSPCs) [1]
The results indicate that human-induced pluripotent stem cells (hiPSCs)-extracellular vesicles (EVs) increase the number of CB-HSPCs that responded to stromal cell-derived factor 1 (SDF-1) with calcium flux, with the highest effect observed after 6 h of treatment with vesicles (Fig. 4C, D)
Few groups have published data showing that EVs isolated from bone marrow (BM)-derived Human mesenchymal stem cells (hMSCs) and osteoblasts may impact on CB cells enhancing their therapeutic efficacy [9, 38, 39]
Summary
Human umbilical cord blood (CB) is a rich source of various stem and progenitor cell types, including non-hematopoietic and hematopoietic stem and progenitor cells (HSPCs) [1]. The clinical application of CB cells for bone marrow (BM) reconstitution in patients suffering from hematological and malignant disorders is a desirable approach because of the available stem cell (SCs) content, convenient collection methods, low immunogenicity, and low risk of graft-versus-host disease [2]. This leads to an increasing number of private and public CB banks, where CB units can be donated and stored for future use [3]. Several strategies for the enhancement of CB-HSPCs functions have been proposed, including ex vivo expansion prior to cell administration, the use of various cytokine cocktails, and coculture systems [2, 6, 7] or pre-treatment with different chemical compounds, e.g., Stem-Regenin-1 [8]
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