Rationale and design of the European multicentre study on Stem Cell therapy in IschEmic Non‐treatable Cardiac diseasE (SCIENCE)

Abstract

Aims Ischaemic heart failure (IHF) patients have a poor prognosis even with current guideline‐derived therapy. Intramyocardial injections of autologous or allogeneic mesenchymal stromal cells might improve cardiac function leading to better clinical outcome. Methods The SCIENCE (Stem Cell therapy in IschEmic Non‐treatable Cardiac diseasE) consortium has initiated a Horizon 2020 funded multicentre phase II study in six European countries. It is a double‐blind, placebo‐controlled trial testing the safety and efficacy of allogeneic Cardiology Stem Cell Centre Adipose‐derived Stromal Cells (CSCC_ASC) from healthy donors or placebo in 138 symptomatic IHF patients. Main inclusion criteria are New York Heart Association class II–III, left ventricular ejection fraction < 45% and N‐terminal pro‐B‐type natriuretic peptide levels > 300 pg/mL. Patients are randomized in a 2:1 pattern to receive intramyocardial injections of either CSCC_ASC or placebo. CSCC_ASC and placebo treatments are prepared centralized at Rigshospitalet in 5 mL vials as an off‐the‐shelf product. Vials are distributed to all clinical partners and stored in nitrogen vapour tanks ready to be used directly after thawing. A total of 100 × 106 CSCC_ASC or placebo are injected directly into viable myocardium in the infarct border zone using the NOGA XP system (BDS, Cordis, Johnson & Johnson, USA). Primary endpoint is a centralized core‐laboratory assessed change in left ventricular end‐systolic volume at 6‐month follow‐up measured by echocardiography. The trial started in January 2017, 58 patients were included and treated until July 2018. Conclusion The SCIENCE trial will provide clinical data on efficacy and safety of intramyocardial cell therapy of allogeneic adipose‐derived stromal cells from healthy donors in patients with IHF.

Bone marrow‐derived mesenchymal stromal cell treatment in patients with ischaemic heart failure: final 4‐year follow‐up of the MSC‐HF trial

“…Looking forward several ongoing MCS trials have gone from using autologous MSC to using allogeneic MSCs . This is done to overcome problems with between‐patient variation in cell yield and culture expansion time and also to overcome the negative effect that patient co‐morbidities such as chronic obstructive pulmonary disease and kidney function have on cell quality …”

Autologous adipose-derived stromal cell treatment for patients with refractory angina (MyStromalCell Trial): 3-years follow-up results

“…Furthermore, CSCC_ASC is being tested in a Danish and European multicentre double-blinded placebo-controlled trial for treatment of patients with ischemic heart failure (EudraCT: 2015-001560-19 and EudraCT: 2015-002929-19, respectively) [25, 26].…”

3D Myocardial Scar Prediction Model Derived from Multimodality Analysis of Electromechanical Mapping and Magnetic Resonance Imaging

“…Both studies highlighted the differences in identification capabilities of diseased myocardium by different EAM parameters and suggest a combination of multiple parameters to further improve identification of diseased or infarcted myocardium. Furthermore, EMM is the clinical standard for trans-endocardial delivery of cardiac regenerative therapy into the myocardial infarct border zone [39] and continues to be used in multiple current studies [3]. A recent publication suggested that EAM-guided LV lead implantation improves response to cardiac resynchronization [40].…”

“…For example, ablation of ventricular tachycardia may require ablation lesions to be placed in and around the myocardial infarction (MI) area to eliminate electrical signals conducted via viable cells contributing to the arrhythmia [2]. Furthermore, in trials evaluating cardiac regenerative therapy, therapeutics are often targeted specifically to the infarct border zone [3]. The current gold standard for infarct imaging is late gadolinium–enhanced magnetic resonance imaging (LGE-MRI).…”