TY - JOUR
T1 - Effect of allogeneic adipose tissue-derived mesenchymal stromal cell treatment in chronic ischaemic heart failure with reduced ejection fraction – the SCIENCE trial
AU - Qayyum, Abbas Ali
AU - van Klarenbosch, Bas
AU - Frljak, Sabina
AU - Cerar, Andraz
AU - Poglajen, Gregor
AU - Traxler-Weidenauer, Denise
AU - Nadrowski, Pawel
AU - Paitazoglou, Christina
AU - Vrtovec, Bojan
AU - Bergmann, Martin W.
AU - Chamuleau, Steven A. J.
AU - Wojakowski, Wojtek
AU - Gyöngyösi, Mariann
AU - Kraaijeveld, Adriaan
AU - the SCIENCE Investigators
AU - Hansen, Kristian Schultz
AU - Vrangbæk, Karsten
AU - Jørgensen, Erik
AU - Helqvist, Steffen
AU - Joshi, Francis Richard
AU - Johansen, Ellen M. nsted
AU - Follin, Bjarke
AU - Juhl, Morten
AU - Højgaard, Lisbeth Drozd
AU - Mathiasen, Anders Bruun
AU - Ekblond, Annette
AU - Haack-Sørensen, Mandana
AU - Kastrup, Jens
N1 - Funding Information: This work was supported by an EU funding as part of the Horizon 2020 program to conduct this randomized multicentre clinical trial (SCIENCE grant no. 643478). The Innovation Fund Denmark grant (CSCC grant no. 6153‐00002A), and Aase and Ejnar Danielsens Foundation. Funding Information: This work was supported by an EU funding as part of the Horizon 2020 program to conduct this randomized multicentre clinical trial (SCIENCE grant no. 643478). The Innovation Fund Denmark grant (CSCC grant no. 6153-00002A), and Aase and Ejnar Danielsens Foundation. Conflict of interest: A.E., M.H.S. and J.K. are inventors of a granted patent (‘STEM CELL THERAPY BASED ON ADIPOSE-DERIVED STEM CELLS’) (WO2017068140A1 EP3365432A1) owned by the Capital Region of Denmark and Rigshospitalet, Copenhagen University Hospital, Denmark. The patent is granted in Europe and Australia. Applications are submitted in Canada, China, Hong Kong, Japan, Korea, and USA. A.E., M.H.S. and J.K. are founder of Cell2Cure ApS, which has a license to commercialise the patent. All other authors have nothing to disclose. Joanna Ciosek, Sebastian Dworowy, Tomasz Jadczyk, Kai Jaquet, Michal Kozłowski, Aleksandra Michalewska-Włudarczyk, Mira van der Naald, Kasper Westinga, Karin Vlaardingerbroek, Ronja Sagalski, Esther Schlegel, Annette Schmidt, Anna Sikora, Dorota Skiba, Mojdeh Lofti, Kirstine Joo Andresen, Rebekka Harary Søndergaard, Louise Frandsen, and Anne Lavigne were actively involved in the conduction of the SCIENCE trial. This work was supported by an EU funding as part of the Horizon 2020 program to conduct this randomized multicentre clinical trial (SCIENCE grant no. 643478). The Innovation Fund Denmark grant (CSCC grant no. 6153-00002A), and Aase and Ejnar Danielsens Foundation. Conflict of interest: A.E., M.H.S. and J.K. are inventors of a granted patent (‘STEM CELL THERAPY BASED ON ADIPOSE-DERIVED STEM CELLS’) (WO2017068140A1 EP3365432A1) owned by the Capital Region of Denmark and Rigshospitalet, Copenhagen University Hospital, Denmark. The patent is granted in Europe and Australia. Applications are submitted in Canada, China, Hong Kong, Japan, Korea, and USA. A.E., M.H.S. and J.K. are founder of Cell2Cure ApS, which has a license to commercialise the patent. All other authors have nothing to disclose. Publisher Copyright: © 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
KW - Adipose tissue derived-mesenchymal stromal cells
KW - Allogeneic therapy
KW - Clinical trial
KW - Heart failure
KW - Ischaemic cardiomyopathy
KW - Stem cells
UR - http://www.scopus.com/inward/record.url?scp=85147353159&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ejhf.2772
DO - https://doi.org/10.1002/ejhf.2772
M3 - Article
C2 - 36644821
SN - 1388-9842
VL - 25
SP - 576
EP - 587
JO - European journal of heart failure
JF - European journal of heart failure
IS - 4
ER -