Autologous endothelial progenitor cell therapy improves right ventricular function in a model of chronic thromboembolic pulmonary hypertension
Authors: Myriam Amsallem
Julien Guihaire
Jennifer Arthur-Ataam
Peter Dorfmüller
Nassim Arouche
Fanny Loisel
Elie Fadel
Benoît Decante
Bastien Provost
Georges Uzan
Olaf Mercier
David Boulate
Journal: Journal of Thoracic and Cardiovascular Surgery (2019)
Discipline: CLINICAL MEDICINE
Keywords: endothelial progenitor cells; pulmonary hypertension; right ventricle; stem cell therapy.
Affiliations: Research and Innovation Unit, Inserm UMR-S 999, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France; Inserm 1197 Research Unit, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France., Research and Innovation Unit, Inserm UMR-S 999, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France., Research and Innovation Unit, Inserm UMR-S 999, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France; Department of Cardiac Surgery, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France., Research and Innovation Unit, Inserm UMR-S 999, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France; Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France., Inserm 1197 Research Unit, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France., Research and Innovation Unit, Inserm UMR-S 999, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France; Department of Pathology, Marie Lannelongue Hospital, Le Plessis Robinson, France., Research and Innovation Unit, Inserm UMR-S 999, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France; Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France; Paris-Sud University and Paris-Saclay University, School of Medicine, Kremlin-Bicêtre, France., Research and Innovation Unit, Inserm UMR-S 999, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France; Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France; Paris-Sud University and Paris-Saclay University, School of Medicine, Kremlin-Bicêtre, France. Electronic address: .

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. 

Retracted: No

PubPeer comments:
 Dear authors, Could you please check Fig.5F, both VEGF and GAPH appear to contain spliced bands, as indicated by the arrows. Could you please provide the original uncropped WB images for review? ![file] ,