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.