The Initial Cardiac Tissue Response to Cryopreserved Allogeneic Adipose Tissue-Derived Mesenchymal Stromal Cells in Rats with Chronic Ischemic Cardiomyopathy
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...
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2021
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oai:doaj.org-article:3b8acc9f596b4907945dad69b47704df2021-11-11T17:12:38ZThe Initial Cardiac Tissue Response to Cryopreserved Allogeneic Adipose Tissue-Derived Mesenchymal Stromal Cells in Rats with Chronic Ischemic Cardiomyopathy10.3390/ijms2221117581422-00671661-6596https://doaj.org/article/3b8acc9f596b4907945dad69b47704df2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11758https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Mesenchymal 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<sup>+</sup> and CD38<sup>+</sup> macrophages (<i>p</i> = 0.047 and <i>p</i> = 0.021), as well as in the CD4/CD8 lymphocyte ratio (<i>p</i> = 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.Bjarke FollinCecilie HoeegLisbeth D. HøjgaardMorten JuhlKaya B. LundKristina B. V. DøssingSimon BentsenIngrid HunterCarsten H. NielsenRasmus S. RipaJens KastrupAnnette EkblondAndreas KjaerMDPI AGarticlemesenchymal stem cellMSCcell therapyheart failuremode of actionmacrophageBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11758, p 11758 (2021) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
mesenchymal stem cell MSC cell therapy heart failure mode of action macrophage Biology (General) QH301-705.5 Chemistry QD1-999 |
| spellingShingle |
mesenchymal stem cell MSC cell therapy heart failure mode of action macrophage Biology (General) QH301-705.5 Chemistry QD1-999 Bjarke 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 The Initial Cardiac Tissue Response to Cryopreserved Allogeneic Adipose Tissue-Derived Mesenchymal Stromal Cells in Rats with Chronic Ischemic Cardiomyopathy |
| description |
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<sup>+</sup> and CD38<sup>+</sup> macrophages (<i>p</i> = 0.047 and <i>p</i> = 0.021), as well as in the CD4/CD8 lymphocyte ratio (<i>p</i> = 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. |
| format |
article |
| author |
Bjarke 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 |
| author_facet |
Bjarke 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 |
| author_sort |
Bjarke Follin |
| title |
The Initial Cardiac Tissue Response to Cryopreserved Allogeneic Adipose Tissue-Derived Mesenchymal Stromal Cells in Rats with Chronic Ischemic Cardiomyopathy |
| title_short |
The Initial Cardiac Tissue Response to Cryopreserved Allogeneic Adipose Tissue-Derived Mesenchymal Stromal Cells in Rats with Chronic Ischemic Cardiomyopathy |
| title_full |
The Initial Cardiac Tissue Response to Cryopreserved Allogeneic Adipose Tissue-Derived Mesenchymal Stromal Cells in Rats with Chronic Ischemic Cardiomyopathy |
| title_fullStr |
The Initial Cardiac Tissue Response to Cryopreserved Allogeneic Adipose Tissue-Derived Mesenchymal Stromal Cells in Rats with Chronic Ischemic Cardiomyopathy |
| title_full_unstemmed |
The Initial Cardiac Tissue Response to Cryopreserved Allogeneic Adipose Tissue-Derived Mesenchymal Stromal Cells in Rats with Chronic Ischemic Cardiomyopathy |
| title_sort |
initial cardiac tissue response to cryopreserved allogeneic adipose tissue-derived mesenchymal stromal cells in rats with chronic ischemic cardiomyopathy |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/3b8acc9f596b4907945dad69b47704df |
| work_keys_str_mv |
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