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

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.

Trans-endocardial delivery of progenitor cells to compromised myocardium using the “needle technique”and risk of myocardial injury

“…This may be partially related to the increased number of injections. The effect we have identified may be applicable to other trials such as, most recently, the SCIENCE study [ 23 ] that unfortunately did not provide troponin levels in relation to trans-endocardial cell delivery.…”

April 2023 at a glance: focus on diagnosis and comorbidities

“…Overall, 133 patients were included and randomized 2:1 to either cell therapy or placebo. Treatment was safe, but the pre‐defined endpoints were not reached and no improvement in cardiac function and symptoms was observed 39 …”

“…Treatment was safe, but the pre-defined endpoints were not reached and no improvement in cardiac function and symptoms was observed. 39…”

Cell therapy for heart failure: lessons learned from SCIENCE

“…In the current issue of the Journal, Qayyum and colleagues report on the final results of the SCIENCE trial, a randomized trial of NOGA XP‐based injection of allogeneic adipose tissue‐derived mesenchymal stem cells (AT‐MSC) in ischaemic HF patients 12 . The group previously conducted the MSC‐HF phase II trial of injection of MSC that differed in the origin (autologous) and source tissue (bone marrow, BM‐MSC) 10 .…”

“…[8][9][10][11] In the current issue of the Journal, Qayyum and colleagues report on the final results of the SCIENCE trial, a randomized trial of NOGA XP-based injection of allogeneic adipose tissue-derived mesenchymal stem cells (AT-MSC) in ischaemic HF patients. 12 The group previously conducted the MSC-HF phase II trial of injection of MSC that differed in the origin (autologous) and source tissue (bone marrow, BM-MSC). 10 The MSC-HF trial, conducted in 60 patients with ischaemic HF, left ventricular ejection fraction (LVEF) <45%, and New York Heart Association (NYHA) functional class II-III, demonstrated a reduction in the primary endpoint of left ventricular end-systolic volume at 12 months (−17 ml vs. placebo, p < 0.0002) in cell-treated patients.…”