4.7 Article

The Initial Cardiac Tissue Response to Cryopreserved Allogeneic Adipose Tissue-Derived Mesenchymal Stromal Cells in Rats with Chronic Ischemic Cardiomyopathy

Journal

Publisher

MDPI
DOI: 10.3390/ijms222111758

Keywords

mesenchymal stem cell; MSC; cell therapy; heart failure; mode of action; macrophage; cardioimmunology

Funding

  1. Aase and Ejnar Danielsen's Fund
  2. Wife Olga Doris Friis' Scholarship
  3. Novo Nordisk Foundation [NNF18SA0034956]

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In a rat model of chronic ischemic cardiomyopathy, treatment with ASC initiated an immune response involving monocytes/macrophages and T-cells, inducing a gene expression pattern associated with angiogenesis and monocyte/macrophage differentiation.
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.

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