A Flex

A Kawamoto

A Margariti

A Minchenko

A Schuh

AG Lindgren

AN Behrens

C Haller

C Hitchon

C Kalka

C Park

CH Hu

D Tasev

DS Steinbrech

DW Losordo

E Colombo

EA Kimbrel

EB Peters

EY Lee

F Liu

H Shimada

I Elcheva

J Jackson

J Kim

J Li

J Rehman

JK Han

JX Yu

K Iida

L Wang

M Ginsberg

MC Yoder

MO Schupp

MP Craig

MP White

OE Simonson

P Donndorf

PV Phuc

Q She

R Morita

RG Shaffer

S Foja

SH Li

SJ Park

SK Cha

SW Kim

T Asahara

T Bogoslovsky

W Suh

WK Nahm

X Shi

Y Yoshida

YY Bai

Z Zhang

Abstract
                Background
                Endothelial progenitor cell (EPC) transplantation is a promising therapy for ischemic diseases such as ischemic myocardial infarction and hindlimb ischemia. However, limitation of EPC sources remains a major obstacle. Direct reprogramming has become a powerful tool to produce EPCs from fibroblasts. Some recent efforts successfully directly reprogrammed human fibroblasts into functional EPCs; however, the procedure efficacy was low. This study therefore aimed to improve the efficacy of direct reprogramming of human fibroblasts to functional EPCs.
              
                Methods
                Human fibroblasts isolated from foreskin were directly reprogrammed into EPCs by viral ETV2 transduction. Reprogramming efficacy was improved by culturing transduced fibroblasts in hypoxia conditions (5 % oxygen). Phenotype analyses confirmed that single-factor ETV2 transduction successfully reprogrammed dermal fibroblasts into functional EPCs.
              
                Results
                Hypoxia treatment during the reprogramming procedure increased the efficacy of reprogramming from 1.21 ± 0.61 % in normoxia conditions to 7.52 ± 2.31 % in hypoxia conditions. Induced EPCs in hypoxia conditions exhibited functional EPC phenotypes similar to those in normoxia conditions, such as expression of CD31 and VEGFR2, and expressed endothelial gene profiles similar to human umbilical vascular endothelial cells. These cells also formed capillary-like networks in vitro.
              
                Conclusion
                Our study demonstrates a new simple method to increase the reprogramming efficacy of human fibroblasts to EPCs using ETV2 and hypoxia.
              </jats:sec

Phuc Van Pham

Ngoc Bich Vu

Hoa Trong Nguyen

Oanh Thuy Huynh

Mai Thi-Hoang Truong

Crossref

Stem Cell Research & Therapy

Significant improvement of direct reprogramming efficacy of fibroblasts into progenitor endothelial cells by ETV2 and hypoxia

https://stemcellres.biomedcentral.com/track/pdf/10.1186/s13287-016-0368-2?site=stemcellres.biomedcentral.com

Significant improvement of direct reprogramming efficacy of fibroblasts into progenitor endothelial cells by ETV2 and hypoxia

Abstract

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