Study of angiogenic cell therapy for progressive pulmonary arterial hypertension: intervention with repeat dosing of eNOS-enhanced EPCs: the SAPPHIRE trial

Duncan J Stewart; Sanjay Mehta; George Chandy; Naushad Hirani; John Granton; Nathan Hambly; John Swiston; Kim Danovitch; Elham Sabri; Antonio Giulivi; David W Courtman; Dean A Fergusson

doi:10.1016/j.healun.2025.05.012

Study of angiogenic cell therapy for progressive pulmonary arterial hypertension: intervention with repeat dosing of eNOS-enhanced EPCs: the SAPPHIRE trial

J Heart Lung Transplant. 2025 Oct;44(10):1663-1667. doi: 10.1016/j.healun.2025.05.012. Epub 2025 May 28.

Authors

Affiliations

¹ Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Department of Cell and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; University of Ottawa Heart Institute, Ottawa, Ontario, Canada. Electronic address: djstewart@ohri.ca.
² Southwest Ontario PH Clinic, Department of Medicine, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada.
³ Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
⁴ Division of Respirology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
⁵ Division of Respirology, Temerty Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁶ Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
⁷ Division of Respirology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
⁸ Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

PMID: 40446884
DOI: 10.1016/j.healun.2025.05.012

Abstract

Pulmonary arterial hypertension (PAH) is characterized by widespread pruning of the distal pulmonary arterial bed, leading to increased pulmonary vascular resistance, right heart failure, and death. PAH patients receiving background therapy were randomized to receive a course of 4 monthly infusions of placebo or angiogenic endothelial progenitor cells (EPCs) transfected with endothelial NO synthase (eNOS) over the first 6-month period for a cumulative dose of 80 M cells. Due to the COVID-19 pandemic, the trial was stopped after 12 of the planned 45 patients were enrolled (five placebo, seven eNOS-EPCs). While the small sample size precluded appropriately powered analyses, a possible difference was seen in 6MWD between the eNOS-EPC and placebo groups over 6 months, with a greater proportion of patients in the cell therapy group achieving a minimal clinically important increase in 6MWD of 33-m (71.4% vs 40%, respectively). Treatment of PAH patients with a course of 4 monthly infusions of eNOS-EPCs was well tolerated and may have resulted in clinical benefit.

Keywords: Cell therapy; Endothelial NO-synthase; Endothelial progenitor cells; Gene therapy; Pulmonary hypertension.

Publication types

Randomized Controlled Trial
Multicenter Study

MeSH terms

Adult
COVID-19 / epidemiology
Disease Progression
Double-Blind Method
Endothelial Progenitor Cells* / transplantation
Female
Humans
Hypertension, Pulmonary* / therapy
Male
Middle Aged
Nitric Oxide Synthase Type III* / genetics
Pulmonary Arterial Hypertension* / therapy
Treatment Outcome

Substances

Nitric Oxide Synthase Type III
NOS3 protein, human