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Biomed Pharmacother. 2021 Nov;143:112186. doi: 10.1016/j.biopha.2021.112186. Epub 2021 Sep 24.

Local intramuscular administration of ANG1 and VEGF genes using plasmid vectors mobilizes CD34+ cells to peripheral tissues and promotes angiogenesis in an animal model.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Jan Paweł Skóra, Maciej Antkiewicz, Diana Kupczyńska, Katarzyna Kulikowska, Bartłomiej Strzelec, Dariusz Janczak, Piotr Barć

Affiliations

  1. Department and Clinic of Vascular, General and Transplantation Surgery, Jan Mikulicz-Radecki University Hospital, Wroclaw Medical University, Wroclaw, Poland.
  2. Department and Clinic of Vascular, General and Transplantation Surgery, Jan Mikulicz-Radecki University Hospital, Wroclaw Medical University, Wroclaw, Poland. Electronic address: [email protected].

PMID: 34649339 DOI: 10.1016/j.biopha.2021.112186

Abstract

INTRODUCTION: Patients with peripheral artery disease have poor prognosis despite advances in vascular surgery. Therefore, attempts have been made at using gene and cell therapy to stimulate angiogenesis in the lower limbs in patients with critical lower limb ischemia (CLI).

METHODS: The study included 30 rats divided into 3 groups. An intramuscular injection of a therapeutic gene or cells in the right hind limb was administered in each group: angiopoietin-1 (ANG1) plasmid in group 1, ANG1/vascular endothelial growth factor (ANG1/VEGF) bicistronic construct in group 2, and naked plasmid in group 3 (control). After 3 months of follow-up, tissue samples were harvested, and vessels that stained positively for CD34 cells were quantified.

RESULTS: The highest CD34+ cell count was noted in the ANG1/VEGF group (98.26 cells), followed by the ANG1 group (80.31) and control group (47.93). The CD34+ cell count was significantly higher in the ANG1/VEGF and ANG1 groups than in the control group. There was no significant difference in the CD34+ cell count between the ANG1/VEGF and ANG1 groups.

CONCLUSION: Our study confirmed that therapy with ANG1 plasmid alone or ANG1/VEGF bicistronic construct is safe and effective in a rat model. The therapy resulted in the recruitment of more CD34+ vascular endothelial cells than in the control group receiving naked plasmid.

Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Keywords: ANG1; CD34+; Gene therapy; VEGF

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