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Randomized Controlled Trial
. 2023 Apr;25(4):576-587.
doi: 10.1002/ejhf.2772. Epub 2023 Jan 31.

Effect of allogeneic adipose tissue-derived mesenchymal stromal cell treatment in chronic ischaemic heart failure with reduced ejection fraction - the SCIENCE trial

Abbas Ali Qayyum  1 , Bas van Klarenbosch  2 , Sabina Frljak  3 , Andraz Cerar  3 , Gregor Poglajen  3 , Denise Traxler-Weidenauer  4 , Pawel Nadrowski  5 , Christina Paitazoglou  6 , Bojan Vrtovec  3 , Martin W Bergmann  6 , Steven A J Chamuleau  2 , Wojtek Wojakowski  5 , Mariann Gyöngyösi  4 , Adriaan Kraaijeveld  2 , Kristian Schultz Hansen  7 , Karsten Vrangbaek  7 , Erik Jørgensen  1 , Steffen Helqvist  1 , Francis Richard Joshi  1 , Ellen Mønsted Johansen  1 , Bjarke Follin  1 , Morten Juhl  1 , Lisbeth Drozd Højgaard  1 , Anders Bruun Mathiasen  1 , Annette Ekblond  1 , Mandana Haack-Sørensen  1 , Jens Kastrup  1 ; SCIENCE Investigators
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Free article
Randomized Controlled Trial

Effect of allogeneic adipose tissue-derived mesenchymal stromal cell treatment in chronic ischaemic heart failure with reduced ejection fraction - the SCIENCE trial

Abbas Ali Qayyum et al. Eur J Heart Fail. 2023 Apr.
Free article

Abstract

Aims: The aim of the SCIENCE trial was to investigate whether a single treatment with direct intramyocardial injections of adipose tissue-derived mesenchymal stromal cells (CSCC_ASCs) was safe and improved cardiac function in patients with chronic ischaemic heart failure with reduced ejection fraction (HFrEF).

Methods and results: The study was a European multicentre, double-blind, placebo-controlled phase II trial using allogeneic CSCC_ASCs from healthy donors or placebo (2:1 randomization). Main inclusion criteria were New York Heart Association (NYHA) class II-III, left ventricular ejection fraction (LVEF) <45%, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels >300 pg/ml. CSCC_ASCs or placebo (isotonic saline) were injected directly into viable myocardium. The primary endpoint was change in left ventricular end-systolic volume (LVESV) at 6-month follow-up measured by echocardiography. A total of 133 symptomatic HFrEF patients were included. The treatment was safe without any drug-related severe adverse events or difference in cardiac-related adverse events during a 3-year follow-up period. There were no significant differences between groups during follow-up in LVESV (0.3 ± 5.0 ml, p = 0.945), nor in secondary endpoints of left ventricular end-diastolic volume (-2.0 ± 6.0 ml, p = 0.736) and LVEF (-1.6 ± 1.0%, p = 0.119). The NYHA class improved slightly within the first year in both groups without any difference between groups. There were no changes in 6-min walk test, NT-proBNP, C-reactive protein or quality of life the first year in any groups.

Conclusion: The SCIENCE trial demonstrated safety of intramyocardial allogeneic CSCC_ASC therapy in patients with chronic HFrEF. However, it was not possible to improve the pre-defined endpoints and induce restoration of cardiac function or clinical symptoms.

Keywords: Adipose tissue derived-mesenchymal stromal cells; Allogeneic therapy; Clinical trial; Heart failure; Ischaemic cardiomyopathy; Stem cells.

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