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Updated: Dec 20, 2025
Delayed Intramyocardial Delivery of Stem Cells after Ischemia Reperfusion Injury in a Murine Model
Published on: September 3, 2020
Intravenously delivered mesenchymal stem cells prevent microvascular obstruction formation after myocardial
Junzhuo Wang1, Ziwei Chen2, Qing Dai2
1Department of Cardiology, Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, China.
Abstract:
Microvascular obstruction (MVO) after primary percutaneous coronary intervention (pPCI) is identified as an independent risk factor for poor prognosis in patients with acute myocardial infarction (AMI). The inflammatory response induced by ischemia and reperfusion (I/R) injury is considered one of the main mechanisms of MVO. Mesenchymal stem cells (MSCs) are a unique stromal cell type that confers an immunomodulatory effect in cardiac disease. The present study aimed to investigate whether immediate intravenous delivery of MSCs could be used as a potential therapeutic method to attenuate MVO formation. A cardiac catheterization-induced porcine model of myocardial I/R injury was established, and allograft MSCs were immediately delivered intravenously. Cardiac magnetic resonance (CMR) imaging was performed on days 2 and 7 after the operation to determine the infarct area, MVO, and cardiac function. The pigs with allograft MSCs showed decreased MVO and infarct size, as well as an improved left ventricular ejection fraction (LVEF). Histological analysis revealed decreased myocyte area, fibrosis, and inflammatory cell infiltration in the peri-infarct zone of pigs with allograft MSCs. Moreover, the concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6) and C-reactive protein (CRP) in the serum were reduced in the allograft MSC group compared to the control group. Flow cytometry indicated decreased natural killer (NK) cells in the peripheral blood and ischemic heart tissue in the pigs with allograft MSCs. In summary, allograft MSCs delivered intravenously and immediately after myocardial I/R injury can attenuate MVO formation in a porcine model through a decline in the number of NK cells in the myocardium.
Insights
Immediate intravenous delivery of mesenchymal stem cells (MSCs) reduced microvascular obstruction (MVO) and improved cardiac function after myocardial ischemia-reperfusion injury in a porcine model. This therapeutic approach attenuated inflammation and decreased natural killer cell presence.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Stem Cell Therapy
Background:
- Microvascular obstruction (MVO) following primary percutaneous coronary intervention (pPCI) is a key predictor of poor prognosis in acute myocardial infarction (AMI) patients.
- Ischemia-reperfusion (I/R) injury triggers an inflammatory response, a primary driver of MVO.
- Mesenchymal stem cells (MSCs) possess immunomodulatory properties beneficial for cardiac conditions.
Purpose of the Study:
- To evaluate the efficacy of immediate intravenous administration of allograft MSCs in mitigating MVO post-myocardial I/R injury.
- To assess the impact of MSCs on infarct size, cardiac function, and inflammatory markers.
Main Methods:
- A porcine model of myocardial I/R injury was created using cardiac catheterization.
- Allograft MSCs were administered intravenously immediately after the I/R procedure.
- Cardiac magnetic resonance (CMR) imaging and histological analyses were performed to assess MVO, infarct size, cardiac function, and inflammation.
Main Results:
- MSCs significantly reduced MVO and infarct size.
- Left ventricular ejection fraction (LVEF) improved in the MSC-treated group.
- Histological examination showed reduced myocyte area, fibrosis, and inflammatory cell infiltration.
- Serum levels of IL-1β, IL-6, and CRP were decreased in the MSC group.
- Flow cytometry revealed a reduction in natural killer (NK) cells in peripheral blood and heart tissue.
Conclusions:
- Immediate intravenous delivery of allograft MSCs effectively attenuates MVO in a porcine model of myocardial I/R injury.
- MSC therapy improves cardiac function and reduces myocardial damage post-I/R.
- The mechanism involves the reduction of NK cell populations and inflammatory markers.
