The initial cardiac tissue response to cryopreserved allogeneic adipose tissue‐derived mesenchymal stromal cells in rats with chronic ischemic cardiomyopathy
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The initial cardiac tissue response to cryopreserved allogeneic adipose tissue‐derived mesenchymal stromal cells in rats with chronic ischemic cardiomyopathy. / Follin, Bjarke; Hoeeg, Cecilie; Højgaard, Lisbeth D.; Juhl, Morten; Lund, Kaya B.; Døssing, Kristina B.V.; Bentsen, Simon; Hunter, Ingrid; Nielsen, Carsten H.; Ripa, Rasmus S.; Kastrup, Jens; Ekblond, Annette; Kjaer, Andreas.
In: International Journal of Molecular Sciences, Vol. 22, No. 21, 11758, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The initial cardiac tissue response to cryopreserved allogeneic adipose tissue‐derived mesenchymal stromal cells in rats with chronic ischemic cardiomyopathy
AU - Follin, Bjarke
AU - Hoeeg, Cecilie
AU - Højgaard, Lisbeth D.
AU - Juhl, Morten
AU - Lund, Kaya B.
AU - Døssing, Kristina B.V.
AU - Bentsen, Simon
AU - Hunter, Ingrid
AU - Nielsen, Carsten H.
AU - Ripa, Rasmus S.
AU - Kastrup, Jens
AU - Ekblond, Annette
AU - Kjaer, Andreas
N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Cardioimmunology
KW - Cell therapy
KW - Heart failure
KW - Macrophage
KW - Mesenchymal stem cell
KW - Mode of action
KW - MSC
U2 - 10.3390/ijms222111758
DO - 10.3390/ijms222111758
M3 - Journal article
C2 - 34769184
AN - SCOPUS:85118119207
VL - 22
JO - International Journal of Molecular Sciences (Online)
JF - International Journal of Molecular Sciences (Online)
SN - 1661-6596
IS - 21
M1 - 11758
ER -
ID: 284195759