PMID- 28052545
OWN - NLM
STAT- MEDLINE
DCOM- 20171109
LR  - 20180210
IS  - 1879-0844 (Electronic)
IS  - 1388-9842 (Linking)
VI  - 19
IP  - 1
DP  - 2017 Jan
TI  - Safety, feasibility and effectiveness of first in-human administration of 
      muscle-derived stem/progenitor cells modified with connexin-43 gene for treatment 
      of advanced chronic heart failure.
PG  - 148-157
LID - 10.1002/ejhf.700 [doi]
AB  - AIMS: To assess the safety and efficacy of transendocardial delivery of 
      muscle-derived stem/progenitor cells with connexin-43 overexpression 
      (Cx-43-MDS/PC) in advanced heart failure (HF). METHODS AND RESULTS: Thirteen 
      subjects with advanced HF, New York Heart Association (NYHA) class II-III were 
      enrolled and treated with targeted injection of Cx-43-MDS/PCs and then monitored 
      for at least 6 months. Overexpression of Cx43 (Cx43+) was significantly higher in 
      all but one subject (Cx43-). Injection of MDS/PCs was associated with significant 
      improvement of exercise capacity: NYHA (3 +/- 0 vs. 1.8 +/- 0.7, P = 0.003), exercise 
      duration (388.69 +/- 141.83 s vs. 462.08 +/- 176.69 s, P = 0.025), peak oxygen 
      consumption (14.38 +/- 3.97 vs. 15.83 +/- 3.74 ml/kg.min, P = 0.022) and oxygen pulse 
      (10.58 +/- 2.89 vs. 18.88 +/- 22.63 mLO(2) /heart rate, P = 0.012). Levels of BNP, 
      left ventricular (LV) ejection fraction and LV end-diastolic volumes tended to 
      improve. There was a significant improvement of the mean unipolar voltage 
      amplitudes measured for the injected segments and the entire left ventricle 
      (9.62 +/- 2.64 vs. 11.62 +/- 3.50 mV, P = 0.014 and 8.83 +/- 2.80 vs. 10.22 +/- 3.41 mV, 
      P = 0.041, respectively). No deaths were documented, Cx43+ (n = 12) subjects 
      presented no significant ventricular arrhythmia; one Cx43- subject suffered from 
      ventricular tachycardia (successfully treated with amiodarone). CONCLUSIONS: 
      Injection of Cx-43-MDS/PCs in patients with severe HF led to significant 
      improvement in exercise capacity and myocardial viability of the injected 
      segments while inducing no significant ventricular arrhythmia. This may arise 
      from improved electrical coupling of the injected cells and injured myocardium 
      and thus better in-situ mechanical cooperation of both cell types. Therefore, 
      further clinical studies with Cx43+ MDS/PCs are warranted.
CI  - (c) 2017 The Authors. European Journal of Heart Failure (c) 2017 European Society of 
      Cardiology.
FAU - Gwizdala, Adrian
AU  - Gwizdala A
AD  - Poznan University of Medical Sciences, 1st Department of Cardiology, Poznan, 
      Poland.
FAU - Rozwadowska, Natalia
AU  - Rozwadowska N
AD  - Department of Reproductive Biology and Stem Cells, Institute of Human Genetics 
      Polish Academy of Sciences, ul. Strzeszynska 32, 60-479, Poznan, Poland.
FAU - Kolanowski, Tomasz Jan
AU  - Kolanowski TJ
AD  - Department of Reproductive Biology and Stem Cells, Institute of Human Genetics 
      Polish Academy of Sciences, ul. Strzeszynska 32, 60-479, Poznan, Poland.
FAU - Malcher, Agnieszka
AU  - Malcher A
AD  - Department of Reproductive Biology and Stem Cells, Institute of Human Genetics 
      Polish Academy of Sciences, ul. Strzeszynska 32, 60-479, Poznan, Poland.
FAU - Cieplucha, Aleksandra
AU  - Cieplucha A
AD  - Poznan University of Medical Sciences, 1st Department of Cardiology, Poznan, 
      Poland.
FAU - Perek, Bartlomiej
AU  - Perek B
AD  - Poznan University of Medical Sciences, Department of Cardiac Surgery, Poznan, 
      Poland.
FAU - Seniuk, Wojciech
AU  - Seniuk W
AD  - Poznan University of Medical Sciences, 1st Department of Cardiology, Poznan, 
      Poland.
FAU - Straburzynska-Migaj, Ewa
AU  - Straburzynska-Migaj E
AD  - Poznan University of Medical Sciences, 1st Department of Cardiology, Poznan, 
      Poland.
FAU - Oko-Sarnowska, Zofia
AU  - Oko-Sarnowska Z
AD  - Poznan University of Medical Sciences, 1st Department of Cardiology, Poznan, 
      Poland.
FAU - Cholewinski, Witold
AU  - Cholewinski W
AD  - Greater Poland Cancer Centre, Nuclear Medicine Department, Poznan, Poland.
FAU - Michalak, Michal
AU  - Michalak M
AD  - Poznan University of Medical Sciences, Department of Statistics, Poznan, Poland.
FAU - Grajek, Stefan
AU  - Grajek S
AD  - Poznan University of Medical Sciences, 1st Department of Cardiology, Poznan, 
      Poland.
FAU - Kurpisz, Maciej
AU  - Kurpisz M
AD  - Department of Reproductive Biology and Stem Cells, Institute of Human Genetics 
      Polish Academy of Sciences, ul. Strzeszynska 32, 60-479, Poznan, Poland.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Heart Fail
JT  - European journal of heart failure
JID - 100887595
RN  - 0 (Connexin 43)
RN  - 0 (GJA1 protein, human)
SB  - IM
MH  - Aged
MH  - Cell Culture Techniques
MH  - Chronic Disease
MH  - Connexin 43/*genetics
MH  - Feasibility Studies
MH  - Female
MH  - Genetic Therapy/*methods
MH  - Heart Failure/physiopathology/*therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Muscle, Skeletal/*cytology
MH  - Myoblasts/*transplantation
MH  - Myocardium
MH  - Pilot Projects
MH  - Prospective Studies
MH  - Regeneration
MH  - Severity of Illness Index
MH  - Stem Cell Transplantation/*methods
MH  - Transfection
MH  - Transplantation, Autologous
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Connexin-43
OT  - Heart failure
OT  - Muscle-derived stem cells
OT  - Transendocardial injection
EDAT- 2017/01/05 06:00
MHDA- 2017/11/10 06:00
CRDT- 2017/01/05 06:00
PHST- 2016/04/22 00:00 [received]
PHST- 2016/09/29 00:00 [revised]
PHST- 2016/11/02 00:00 [accepted]
PHST- 2017/01/05 06:00 [entrez]
PHST- 2017/01/05 06:00 [pubmed]
PHST- 2017/11/10 06:00 [medline]
AID - 10.1002/ejhf.700 [doi]
PST - ppublish
SO  - Eur J Heart Fail. 2017 Jan;19(1):148-157. doi: 10.1002/ejhf.700.