Journal Article

Human Muse cells reduce myocardial infarct size and improve cardiac function without causing arrythmias in a swine model of acute myocardial infarction

Shibata, Sanae, Minatoguchi, Shingo, Minatoguchi, Shinya, Okura, Hiroyuki, Baba, Shinya, Takashima, Satoshi, Dezawa, Mari, Wakao, Shohei, Yamada, Yoshihisa

2022

Overview

We recently reported that multilineage-differentiating stress enduring (Muse) cells intravenously administered after acute myocardial infarction (AMI), selectively engrafted to the infarct area, spontaneously differentiated into cardiomyocytes and vessels, reduced the infarct size, improved the left ventricular (LV) function and remodeling in rabbits. We aimed to clarify the efficiency of Muse cells in a larger animal AMI model of mini-pigs using a semi-clinical grade human Muse cell product. Mini-pigs underwent 30 min of coronary artery occlusion followed by 2 weeks of reperfusion. Semi-clinical grade human Muse cell product (1x107, Muse group, n = 5) or saline (Vehicle group, n = 7) were intravenously administered at 24 h after reperfusion. The infarct size, LV function and remodeling were evaluated by echocardiography. Arrhythmias were evaluated by an implantable loop recorder. The infarct size was significantly smaller in the Muse group (10.5±3.3%) than in the Vehicle group (21.0±2.0%). Both the LV ejection fraction and fractional shortening were significantly greater in the Muse group than in the Vehicle group. The LV end-systolic and end-diastolic dimensions were significantly smaller in the Muse group than in the Vehicle group. Human Muse cells homed into the infarct border area and expressed cardiac troponin I and vascular endothelial CD31. No arrhythmias and no blood test abnormality were observed. Muse cell product might be promising for AMI therapy based on the efficiency and safety in a mini-pig AMI.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Alprostadil / Anesthesiology / Animals / Arrhythmia / Arrhythmias, Cardiac / Biology and Life Sciences / Blood pressure / Blood tests / Blood vessels / Calcium-binding protein / Cardiac arrhythmia / Cardiac function / Cardiology / Cardiomyocytes / Cell differentiation / Cell size / Complications and side effects / Coronary artery / Coronary vessels / Disease Models, Animal / Echocardiography / Electrocardiography / Health aspects / Heart / Heart attack / Heart attacks / Heart rate / Histology / Hogs / Humans / Ischemia / Laboratory animals / Medicine / Medicine and Health Sciences / Mesenchymal stem cells / Myocardial Infarction / Occlusion / Ostomy / Rabbits / Reperfusion / Research and Analysis Methods / Risk factors / Stem cells / Swine / Swine, Miniature / Teaching hospitals / Troponin / Troponin I / University graduates / Veins & arteries / Ventricle / Ventricular Function, Left