Conditioned medium from human umbilical vein endothelial cells markedly improves the proliferation and differentiation of circulating endothelial progenitors.
Circulating endothelial progenitor cells (EPCs) have been suggested as a precious source for generating functionally competent endothelial cells (ECs), candidate for various clinical applications. However, the paucity of these progenitor cells and the technical difficulties for their in vitro growth represent a main limitation to their use. In the present study we hypothesized that the paracrine effects of human umbilical vein endothelial cells (HUVECs) may improve endothelial cell generation from cord blood (CB) EPCs. In line with this hypothesis we showed that HUVEC conditioned medium (CM) or co-culture with HUVECs markedly improved the proliferation and differentiation and delayed the senescence of CB EPCs. The endothelial-promoting effect of CM seems to be related to smaller vesicles including exosomes (sEV/exo) contained in this medium and transferred to CB CD34(+) EPCs: in fact, purified preparations of sEV/exo isolated from CM mimicked the effect of CM to sustain endothelial formation. These observations provided the interesting indication that mature ECs exert a stimulatory effect on endothelial cell differentiation from CD34(+) cells.
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 200, 00161 Rome, Italy.
Germana
G
Castelli
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 200, 00161 Rome, Italy.
Isabella
I
Parolini
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 200, 00161 Rome, Italy.
Anna Maria
AM
Cerio
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 200, 00161 Rome, Italy.
Agnese
A
D'Angiò
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 200, 00161 Rome, Italy.
Luca
L
Pasquini
Department of Infectious, Parasitic and Immune-mediates Diseases, Istituto Superiore di Sanità, Viale Regina Elena 200, 00161 Rome, Italy.
Maria
M
Carollo
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 200, 00161 Rome, Italy.
Massimo
M
Sargiacomo
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 200, 00161 Rome, Italy. Electronic address: ugo.testa@iss.it.
Ugo
U
Testa
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 200, 00161 Rome, Italy.
Elvira
E
Pelosi
D018952:Antigens, CD34; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology; D055354:Exosomes; D005312:Fetal Blood / Q000166:cytology; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D019899:Paracrine Communication
D018952:Antigens, CD34; D017077:Culture Media, Conditioned