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. 2021 Dec 16;8:793040. doi: 10.3389/fmed.2021.793040

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Copyright © 2021 Laurenzana, Trino, Lamorte, De Stradis, Santodirocco, Sgambato, De Luca and Caivano.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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MM-EV effect on both HSPC cell cycle and differentiation and CD123 expression on HSCs. (A) Model of human lympho-myeloid differentiation. Stem/early progenitors include hematopoietic stem cells (HSCs), multipotent progenitors (MPP), lymphoid-primed multipotent progenitor (LMPP), multi-lymphoid progenitor (MLP); late progenitors include common myeloid progenitor (CMP), megakaryocyte erythroid progenitor (MEP), granulocyte macrophage progenitor (GMP), and B/NK progenitors (B/NK prog). Arrows indicate the derivation. (B) Representative cytofluorometric dot plots of populations in HSPCs treated or not with MM-EVs for 20 h. The cell percentage of each population was reported in dot plots. (C) Percentage of CD34⁺, stem/early, and late progenitors after 20 h of treatment with two doses of MM-EVs (MM-EVs 200 μg, MM-EVs 400 μg). (D) Percentage of cells in G0/G1, S, and G2/M phases on CD34⁺, CD34⁺/CD38⁻, and CD34⁺/CD38⁺ cells after treatment with two doses of MM-derived EVs. (E) Percentage of different HSPC populations after treatment with two doses of MM-EVs. (F) Percentage of CD123 expression on HSCs after treatment with two doses of MM-derived EVs. On the left representative histogram of CD123 mean fluorescence intensity (x-axis) in control (CTRL, blue) and treated HSPCs (MM-EVs 400 μg, red). The bar graphs represent the average with standard deviation from three independent experiments; ^* indicates p = 0.05. MM, multiple myeloma; EVs, Extracellular vesicles; HSPC, hematopoietic stem and progenitor cells.