PMID- 32762286 OWN - NLM STAT- MEDLINE DCOM- 20210903 LR - 20210903 IS - 1557-8534 (Electronic) IS - 1547-3287 (Linking) VI - 29 IP - 20 DP - 2020 Oct 15 TI - Immediate Intracoronary Delivery of Human Umbilical Cord Mesenchymal Stem Cells Reduces Myocardial Injury by Regulating the Inflammatory Process Through Cell-Cell Contact with T Lymphocytes. PG - 1331-1345 LID - 10.1089/scd.2019.0264 [doi] AB - Inflammatory response regulation is a mechanism through which human umbilical cord mesenchymal stem cells (HUCMSCs) improve myocardial ischemia reperfusion injury (IRI); however, the timing of HUCMSC delivery to achieve maximum effectiveness is controversial. To investigate the effects of HUCMSC delivery on the acute inflammatory stage of IRI, we transplanted HUCMSCs or HUCMSCs with cyclosporin A (CsA) through the coronary artery simultaneously during ischemia reperfusion in pigs. Ferumoxytol-labeled HUCMSCs (HUCMSC), HUCMSCs with cyclosporin A (HUCMSC+CsA), and PBS (control) groups were investigated to evaluate the homing of transplanted cells and changes in infarct features, cardiac activity, and inflammatory response at three time points post-transplantation. Animals were sacrificed 2 weeks later for histological analysis of the hearts. We detected Prussian blue-dyed granules distributed around T lymphocyte clusters in the infarct area in the HUCMSC group. Infarct size and collagen deposition in the infarct area were lower in the HUCMSC group than in the control and HUCMSC+CsA groups. Cardiac function was mildly impaired in both the control and HUCMSC groups, whereas added CsA had a more severe impact. The levels of proinflammatory markers were lower in the HUCMSC group than in the control group at 24-h follow-up, and the difference was more significant after adding CsA. There were more CD3(+) T lymphocytes and Foxp3(+) Tregs in the HUCMSC group infarct area than in the other two groups. Proliferation rate of T lymphocytes was higher in the HUCMSC group than in the other two groups. Indirect co-culture experiments in vitro showed that MSCs promoted the generation of CD4(+)CD25(+) Foxp3(+)Tregs through a paracrine mechanism. These results indicate that immediate intracoronary delivery of HUCMSCs after ischemia reperfusion can reduce acute myocardial IRI and promote myocardial repair, mainly through T lymphocyte interactions to regulate the intense inflammatory response during the acute inflammatory stage. FAU - Liu, Chen AU - Liu C AD - Department of Cardiology, Affiliated Hospital of Yangzhou University, Yangzhou City, People's Republic of China. FAU - Kang, Li-Na AU - Kang LN AD - Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing City, People's Republic of China. FAU - Chen, Fu AU - Chen F AD - Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing City, People's Republic of China. FAU - Mu, Dan AU - Mu D AD - Department of Radiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing City, People's Republic of China. FAU - Shen, Song AU - Shen S AD - Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing City, People's Republic of China. FAU - Wang, Kun AU - Wang K AD - Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing City, People's Republic of China. FAU - Hu, Jia-Xin AU - Hu JX AD - Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing City, People's Republic of China. FAU - Xie, Jun AU - Xie J AD - Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing City, People's Republic of China. FAU - Xu, Biao AU - Xu B AD - Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing City, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200827 PL - United States TA - Stem Cells Dev JT - Stem cells and development JID - 101197107 RN - 0 (Biomarkers) RN - 9007-34-5 (Collagen) RN - XM0M87F357 (Ferrosoferric Oxide) SB - IM MH - Animals MH - Biomarkers/blood MH - *Cell Communication MH - Cell Proliferation MH - Collagen/metabolism MH - Disease Models, Animal MH - Female MH - Ferrosoferric Oxide/metabolism MH - Heart Ventricles/pathology/physiopathology MH - Inflammation/blood/*pathology MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*cytology MH - Myocardial Infarction/pathology/physiopathology/therapy MH - Myocardium/*pathology MH - Paracrine Communication MH - Perfusion MH - Swine MH - Swine, Miniature MH - Systole MH - T-Lymphocytes/*immunology MH - Umbilical Cord/*cytology OTO - NOTNLM OT - T lymphocytes OT - cyclosporin A OT - human umbilical cord mesenchymal stem cells OT - inflammation OT - myocardial ischemia reperfusion injury EDAT- 2020/08/09 06:00 MHDA- 2021/09/04 06:00 CRDT- 2020/08/09 06:00 PHST- 2020/08/09 06:00 [pubmed] PHST- 2021/09/04 06:00 [medline] PHST- 2020/08/09 06:00 [entrez] AID - 10.1089/scd.2019.0264 [doi] PST - ppublish SO - Stem Cells Dev. 2020 Oct 15;29(20):1331-1345. doi: 10.1089/scd.2019.0264. Epub 2020 Aug 27.