PMID- 36638837
OWN - NLM
STAT- MEDLINE
DCOM- 20230330
LR  - 20230406
IS  - 2055-5822 (Electronic)
IS  - 2055-5822 (Linking)
VI  - 10
IP  - 2
DP  - 2023 Apr
TI  - Danish phase II trial using adipose tissue derived mesenchymal stromal cells for 
      patients with ischaemic heart failure.
PG  - 1170-1183
LID - 10.1002/ehf2.14281 [doi]
AB  - AIMS: Patients suffering from chronic ischaemic heart failure with reduced left 
      ventricular ejection fraction (HFrEF) have reduced quality-of-life, repetitive 
      hospital admissions, and reduced life expectancy. Allogeneic cell therapy is 
      currently investigated as a potential treatment option after initially 
      encouraging results from clinical autologous and allogeneic trials in patients 
      with HFrEF. We aimed to investigate the allogeneic Cardiology Stem Cell Centre 
      Adipose tissue derived mesenchymal Stromal Cell product (CSCC_ASC) as an add-on 
      therapy in patients with chronic HFrEF. METHODS AND RESULTS: This is a Danish 
      multi-centre double-blinded placebo-controlled phase II study with direct 
      intra-myocardial injections of allogeneic CSCC_ASC. A total of 81 HFrEF patients 
      were included and randomized 2:1 to CSCC_ASC or placebo injections. The inclusion 
      criteria were reduced left ventricular ejection fraction (LVEF </= 45%), New York 
      Heart Association (NYHA) class II-III despite optimal anti-congestive heart 
      failure medication and no further revascularization options. Injections of 0.3 mL 
      CSCC_ASC (total cell dose 100 x 10(6) ASCs) (n = 54) or isotonic saline (n = 27) 
      were performed into the viable myocardium in the border zone of infarcted tissue 
      using the NOGA Myostar(R) catheter (Biological Delivery System, Cordis, Johnson & 
      Johnson, USA). The primary endpoint, left ventricular end systolic volume 
      (LVESV), was evaluated at 6-month follow-up. The safety was measured during a 
      3-years follow-up period. RESULTS: Mean age was 67.0 +/- 9.0 years and 
      66.6 +/- 8.1 years in the ASC and placebo groups, respectively. LVESV was unchanged 
      from baseline to 6-month follow-up in the ASC (125.7 +/- 68.8 mL and 
      126.3 +/- 72.5 mL, P = 0.827) and placebo (134.6 +/- 45.8 mL and 135.3 +/- 49.6 mL, 
      P = 0.855) group without any differences between the groups (0.0 mL (95% CI -9.1 
      to 9.0 mL, P = 0.992). Neither were there significant changes in left ventricular 
      end diastolic volume or LVEF within the two groups or between groups -5.7 mL (95% 
      CI -16.7 to 5.3 mL, P = 0.306) and -1.7% (95% CI -4.4. to 1.0, P = 0.212), 
      respectively). NYHA classification and 6-min walk test did not alter 
      significantly in the two groups (P > 0.05). The quality-of-life, total symptom, 
      and overall summary score improved significantly only in the ASC group but not 
      between groups. There were 24 serious adverse events (SAEs) in the ASC group and 
      11 SAEs in the placebo group without any significant differences between the two 
      groups at 1-year follow-up. Kaplan-Meier plot using log-rank test of combined 
      cardiac events showed an overall mean time to event of 30 +/- 2 months in the ASC 
      group and 29 +/- 2 months in the placebo group without any differences between the 
      groups during the 3 years follow-up period (P = 0.994). CONCLUSIONS: 
      Intramyocardial CSCC_ASC injections in patients with chronic HFrEF were safe but 
      did not improve myocardial function or structure, nor clinical symptoms.
CI  - (c) 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on 
      behalf of European Society of Cardiology.
FAU - Qayyum, Abbas Ali
AU  - Qayyum AA
AUID- ORCID: 0000-0002-1620-0002
AD  - Department of Cardiology and Cardiology Stem Cell Centre, The Heart Centre, 
      Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
AD  - Department of Cardiology, Hvidovre Hospital, University of Copenhagen, 
      Copenhagen, Denmark.
FAU - Mouridsen, Mette
AU  - Mouridsen M
AD  - Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, 
      Copenhagen, Denmark.
FAU - Nilsson, Brian
AU  - Nilsson B
AD  - Department of Cardiology, Hvidovre Hospital, University of Copenhagen, 
      Copenhagen, Denmark.
FAU - Gustafsson, Ida
AU  - Gustafsson I
AD  - Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, 
      Copenhagen, Denmark.
FAU - Schou, Morten
AU  - Schou M
AD  - Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, 
      Copenhagen, Denmark.
FAU - Nielsen, Olav Wendelboe
AU  - Nielsen OW
AD  - Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, 
      Copenhagen, Denmark.
FAU - Hove, Jens Dahlgaard
AU  - Hove JD
AD  - Department of Cardiology, Hvidovre Hospital, University of Copenhagen, 
      Copenhagen, Denmark.
FAU - Mathiasen, Anders Bruun
AU  - Mathiasen AB
AD  - Department of Cardiology and Cardiology Stem Cell Centre, The Heart Centre, 
      Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
FAU - Jorgensen, Erik
AU  - Jorgensen E
AD  - Department of Cardiology and Cardiology Stem Cell Centre, The Heart Centre, 
      Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
FAU - Helqvist, Steffen
AU  - Helqvist S
AD  - Department of Cardiology and Cardiology Stem Cell Centre, The Heart Centre, 
      Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
FAU - Joshi, Francis Richard
AU  - Joshi FR
AD  - Department of Cardiology and Cardiology Stem Cell Centre, The Heart Centre, 
      Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
FAU - Johansen, Ellen Monsted
AU  - Johansen EM
AD  - Department of Cardiology and Cardiology Stem Cell Centre, The Heart Centre, 
      Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
FAU - Follin, Bjarke
AU  - Follin B
AD  - Department of Cardiology and Cardiology Stem Cell Centre, The Heart Centre, 
      Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
FAU - Juhl, Morten
AU  - Juhl M
AD  - Department of Cardiology and Cardiology Stem Cell Centre, The Heart Centre, 
      Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
FAU - Hojgaard, Lisbeth Drozd
AU  - Hojgaard LD
AD  - Department of Cardiology and Cardiology Stem Cell Centre, The Heart Centre, 
      Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
FAU - Haack-Sorensen, Mandana
AU  - Haack-Sorensen M
AD  - Department of Cardiology and Cardiology Stem Cell Centre, The Heart Centre, 
      Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
FAU - Ekblond, Annette
AU  - Ekblond A
AD  - Department of Cardiology and Cardiology Stem Cell Centre, The Heart Centre, 
      Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
FAU - Kastrup, Jens
AU  - Kastrup J
AD  - Department of Cardiology and Cardiology Stem Cell Centre, The Heart Centre, 
      Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
LA  - eng
SI  - ClinicalTrials.gov/NCT03092284
SI  - EudraCT/2015-001560-19
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20230113
PL  - England
TA  - ESC Heart Fail
JT  - ESC heart failure
JID - 101669191
SB  - IM
MH  - Humans
MH  - Middle Aged
MH  - Aged
MH  - *Heart Failure/therapy
MH  - *Myocardial Ischemia/complications/therapy
MH  - Stroke Volume
MH  - Ventricular Function, Left
MH  - *Mesenchymal Stem Cell Transplantation/methods
MH  - *Mesenchymal Stem Cells
MH  - Denmark
PMC - PMC10053281
OTO - NOTNLM
OT  - Adipose tissue derived mesenchymal stromal cells
OT  - Allogeneic cell therapy
OT  - Heart failure
OT  - Ischaemic heart disease
OT  - Randomized clinical trial
OT  - Stem cell
COIS- Jens Kastrup, Annette Ekblond and Mandana Haack-Sorensen 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. Jens Kastrup, Annette Ekblond, and Mandana Haack-Sorensen 
      are founders of Cell2Cure ApS, which has a licence to commercialize the patent. 
      The authors declare no conflict of interest except the above mentioned.
EDAT- 2023/01/14 06:00
MHDA- 2023/03/30 06:11
PMCR- 2023/01/13
CRDT- 2023/01/13 19:22
PHST- 2022/12/10 00:00 [revised]
PHST- 2022/09/10 00:00 [received]
PHST- 2022/12/15 00:00 [accepted]
PHST- 2023/03/30 06:11 [medline]
PHST- 2023/01/14 06:00 [pubmed]
PHST- 2023/01/13 19:22 [entrez]
PHST- 2023/01/13 00:00 [pmc-release]
AID - EHF214281 [pii]
AID - 10.1002/ehf2.14281 [doi]
PST - ppublish
SO  - ESC Heart Fail. 2023 Apr;10(2):1170-1183. doi: 10.1002/ehf2.14281. Epub 2023 Jan 
      13.