Abstract
Mesenchymal stromal cells have proven capable of improving cardiac pump function in patients with chronic heart failure, yet little is known about their mode of action. The aim of the study was to investigate the short-term effect of cryopreserved allogeneic rat adipose tissue-derived stromal cells (ASC) on cardiac composition, cellular subpopulations, and gene transcription in a rat model of chronic ischemic cardiomyopathy (ICM). Myocardial infarction (MI) was induced by permanent ligation of the left anterior descending coronary artery. After 6 weeks, the rats were treated with ASCs, saline, or no injection, using echo-guided trans-thoracic intramyocardial injections. The cardiac tissue was subsequently collected for analysis of cellular subpopulations and gene transcription 3 and 7 days after treatment. At day 3, an upregulation of genes associated with angiogenesis were present in the ASC group. On day 7, increases in CCR2+ and CD38+ macrophages (p = 0.047 and p = 0.021), as well as in the CD4/CD8 lymphocyte ratio (p = 0.021), were found in the ASC group compared to the saline group. This was supported by an upregulation of genes associated with monocytes/macrophages. In conclusion, ASC treatment initiated an immune response involving monocytes/macrophages and T-cells and induced a gene expression pattern associated with angiogenesis and monocyte/macrophage differentiation.
Highlights
Heart failure affects millions of people worldwide and causes high morbidity and mortality [1,2]
The phenotype of the adipose tissuederived stromal cells (ASC) was determined by flow cytometry on the basis of the recommendations of the International Society for Cellular Therapy (ISCT) [13,14]
The mode of action (MoA) of mesenchymal stromal cells (MSCs) therapy for cardiac regeneration has been extensively discussed for years [1,27,28,29]
Summary
Heart failure affects millions of people worldwide and causes high morbidity and mortality [1,2]. Most of these clinical cases of heart failure are caused by ischemic cardiomyopathy (ICM) [3]. Through the past two decades, cell therapy has been found to be a potential new treatment option for patients with ischemic heart failure. Treatments using mesenchymal stromal cells (MSCs) are the furthest in clinical translation, where the first phase III study was recently concluded (NCT02032004).
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