Original research

Biomedical Research and Therapy

, 3:45

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Hepatocyte growth factor improves direct reprogramming of fibroblasts towards endothelial progenitor cells via ETV2 transduction

  • Phuc Van PhamAffiliated withLaboratory of Stem Cell Research and Application, University of Sciences, Vietnam National University Email author 
  • , Ngoc Bich VuAffiliated withLaboratory of Stem Cell Research and Application, University of Sciences, Vietnam National University
  • , Mai Thi-Hoang TruongAffiliated withLaboratory of Stem Cell Research and Application, University of Sciences, Vietnam National University
  • , Oanh Thuy HuynhAffiliated withLaboratory of Stem Cell Research and Application, University of Sciences, Vietnam National University
  • , Hoa Trong NguyenAffiliated withLaboratory of Stem Cell Research and Application, University of Sciences, Vietnam National University
  • , Hieu Liem PhamAffiliated withDepartment of Plastic and Aesthetic Surgery, Pham Ngoc Thach University of Medicine
  • , Ngoc Kim PhanAffiliated withLaboratory of Stem Cell Research and Application, University of Sciences, Vietnam National University

Abstract

Introduction:

Human fibroblasts can be differentiated into endothelial progenitor cells by direct reprogramming via ETV-2 transfection. Previously, we have shown that the efficacy of direct reprogramming can be enhanced by hypoxia treatment. In this study, we aim to investigate whether the efficacy of direct reprogramming of fibroblasts into EPCs via Ets variant gene 2 (ETV2) transfection can be increased with hepatocyte growth factor (HGF) treatment.

Methods:

Foreskin-derived fibroblasts were cultured in standard medium (DMEM/F12 supplemented with fetal bovine serum). They were then transduced with a viral vector expressing ETV2 in culture medium supplemented with HGF. The transduced fibroblasts were cultured in endothelial cell medium supplemented with HGF for 28 days. The efficacy of direct reprogramming was evaluated based on expression of CD31 and VEGFR2 markers by transduced cells. Phenotypic and functional characterization of induced EPCs were also confirmed by expression of particular genes and in vitro angiogenesis assays.

Results:

Our results showed that HGF significantly increased the efficacy of direct reprogramming of fibroblasts towards EPCs via ETV2 transcription factors; efficiency increased from 5.41±1.51% for ETV2 transduction alone to 12.31±2.15% for ETV2 transduction combined with HGF treatment.

Conclusion:

These findings suggest the rationale for combined use of ETV2 and HGF in direct in vitro reprogramming of fibroblasts into EPCs.

Keywords:

ETV2 direct reprogramming hepatocyte growth factor endothelial progenitor cell fibroblasts pluripotent stem cells