Autologous endothelial progenitor cell therapy improves right ventricular function in a model of chronic thromboembolic pulmonary hypertension.

Abstract

BACKGROUND:

Right ventricular (RV) failure is the main prognostic factor in pulmonary hypertension, and ventricular capillary density (CD) has been reported to be a marker of RV maladaptive remodeling and failure. Our aim was to determine whether right intracoronary endothelial progenitor cell (EPC) infusion can improve RV function and CD in a piglet model of chronic thromboembolic pulmonary hypertension (CTEPH).

METHODS:

We compared 3 groups: sham (n = 5), CTEPH (n = 6), and CTEPH with EPC infusion (CTEPH+EPC; n = 5). After EPC isolation from CTEPH+EPC piglet peripheral blood samples at 3 weeks, the CTEPH and sham groups underwent right intracoronary infusion of saline, and the CTEPH+EPC group received EPCs at 6 weeks. RV function, pulmonary hemodynamics, and myocardial morphometry were investigated in the animals at 10 weeks.

RESULTS:

After EPC administration, the RV fractional area change increased from 32.75% (interquartile range [IQR], 29.5%-36.5%) to 39% (IQR, 37.25%-46.50%; P = .030). The CTEPH+EPC piglets had reduced cardiomyocyte surface areas (from 298.3 μm2 [IQR, 277.4-335.3 μm2] to 234.6 μm2 (IQR, 211.1-264.7 μm2; P = .017), and increased CD31 expression (from 3.12 [IQR, 1.27-5.09] to 7.14 [IQR, 5.56-8.41; P = .017). EPCs were found in the RV free wall at 4 and 24 hours after injection but not 4 weeks later.

CONCLUSIONS:

Intracoronary infusion of EPC improved RV function and CD in a piglet model of CTEPH. This novel cell-based therapy might represent a promising RV-targeted treatment in patients with pulmonary hypertension.

• Authors: Fanny Loisel, Bastien Provost, Julien Guihaire, David Boulate, Nassim Arouche, Myriam Amsallem, Jennifer Arthur-Ataam, Benoît Decante, Peter Dorfmüller, Elie Fadel, Georges Uzan, Olaf Mercier
• Journal: The Journal of thoracic and cardiovascular surgery (J Thorac Cardiovasc Surg) Vol. 157 Issue 2 Pg. 655-666.e7 (02 2019) ISSN: 1097-685X [Electronic] United States
• PMID: 30669226 (Publication Type: Journal Article, Video-Audio Media)
• Copyright: Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Topics

• Animals
• Animals, Newborn
• Arterial Pressure
• Cells, Cultured
• Disease Models, Animal
• Endothelial Progenitor Cells (transplantation)
• Neovascularization, Physiologic
• Pulmonary Arterial Hypertension (etiology, physiopathology, surgery)
• Pulmonary Embolism (complications, physiopathology)
• Recovery of Function
• Stem Cell Transplantation
• Sus scrofa
• Time Factors
• Transplantation, Autologous
• Ventricular Dysfunction, Right (etiology, physiopathology, prevention & control)
• Ventricular Function, Right
• Ventricular Remodeling