Abstract
Background & Aim CD34+cells transplantation has shown therapeutic angiogenesis efficacy in treating critical limb ischemia. Hypoxic preconditioning can increase the proangiogenic ability. As the main component of the paracrine secretion of CD34+ cells, CD34+ cell exosome (CD34-Exo) plays an important role. In this research, we aim to investigate the proangiogenic mechanism of hypoxic preconditioned CD34 exosome (HCC34-Exo) at the level of exsosomal miRNA. Methods, Results & Conclusion RNAseq screen showed 3.40±2.85 (means±standrad deviations) folds (n=6) of mi-RNA-387a-5p in the HCC34-Exo than in the normoxic preconditioned CD34+ cell exosomes (NCC34-Exo), and this was validated by qRT-PCR. In vitro experiments such as transwell co-culture model, exosome secretion-blocked experiment, exosome tracking experiment demonstrated that miRNA-378a-5p was directly transferred from the CD34+ cells through exosomes of CD34+ cells to human umbilical vein endothelial cells (HUVECs). Tube formation experiment demonstrated the enhancement of the HUVECs function, significant increase was observed concerning branching points in HCC34-Exo group, which equals to 2.15±0.46 folds of that in blank control group, 1.80±0.62 folds of that in anti-miRNA-378 HCC34-Exo group and 1.32±0.34 folds of that in NCC-Exo group (all p Our results have showed that HCC34 might promote therapeutic angiogenesis in ischemic tissue through exosomal miR-378-5p. Identification of the mechanism will provide important theoretical evidence for the therapeutic efficacy of HCC34 and its exsosomal miRNA in treating critical limb ischemia and may offer a new idea for potential treatment strategies in the future.
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