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

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.
AuthorsBjarke Follin, Cecilie Hoeeg, Lisbeth D Højgaard, Morten Juhl, Kaya B Lund, Kristina B V Døssing, Simon Bentsen, Ingrid Hunter, Carsten H Nielsen, Rasmus S Ripa, Jens Kastrup, Annette Ekblond, Andreas Kjaer
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 21 (Oct 29 2021) ISSN: 1422-0067 [Electronic] Switzerland
PMID34769184 (Publication Type: Journal Article)
Topics
  • Allogeneic Cells (cytology)
  • Animals
  • Cells, Cultured
  • Cryopreservation (methods)
  • Male
  • Mesenchymal Stem Cell Transplantation (methods)
  • Mesenchymal Stem Cells (cytology)
  • Myocardial Infarction (physiopathology, therapy)
  • Myocardial Ischemia (physiopathology, therapy)
  • Rats
  • Rats, Inbred Lew

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