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Delayed Intramyocardial Delivery of Stem Cells after Ischemia Reperfusion Injury in a Murine Model
Published on: September 3, 2020
Central zone of myocardial infarction: a neglected target area for heart cell therapy
Peifeng Jin1, Enshi Wang, Ye-Huan Wang
1Department of Surgery and Research Center for Cardiac Regenerative Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Insights
Transplanting bone marrow mesenchymal stem cells (BMSCs) into the central zone of myocardial infarction (MI) promotes angiogenesis and improves scar thickness. Multiple injection sites (border and central zones) are recommended for effective cell therapy in MI.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Stem Cell Biology
Background:
- Myocardial infarction (MI) leads to significant cardiac damage and impaired heart function.
- Cell therapy is a promising approach for cardiac repair, but optimal delivery sites remain debated.
- Understanding the fate and impact of transplanted cells in different infarct zones is crucial for therapeutic efficacy.
Purpose of the Study:
- To investigate the survival and impact of transplanted bone marrow mesenchymal stem cells (BMSCs) in the central zone of myocardial infarction (MI).
- To clarify the relationship between injection site (border vs. central zone) and the efficacy of cell therapy post-MI.
- To evaluate the potential of BMSCs to promote angiogenesis, myogenesis, and reverse cardiac remodeling.
Main Methods:
- Myocardial infarction induced by coronary ligation in female rats.
- Direct injection of labeled male BMSCs into the border zone (BZC) or central zone (CZC) of MI.
- Assessment of cell survival, apoptosis, angiogenesis, myogenesis, cardiac function, and morphometry using qPCR, TUNEL, caspase-3, immunofluorescence, echocardiography, and Masson's Trichrome staining.
Main Results:
- Transplanted BMSCs did not migrate between MI zones.
- BMSCs in the central zone showed comparable survival and apoptosis rates to those in the border zone.
- Cell delivery to the central zone promoted angiogenesis and myogenic differentiation, increased scar thickness, and trended towards reverse remodeling.
Conclusions:
- The central zone of MI is a viable site for cell transplantation and should not be overlooked in cell-based therapies.
- While central zone injection alone did not improve overall heart function compared to border zone injection, it offered regenerative benefits.
- Multiple site injection (border and central zones) is recommended for maximizing the therapeutic potential of cell transplantation in myocardial infarction.
Abstract:
The purpose of this study was to investigate the fate of transplanted cells in the central zone of myocardial infarction (MI), and to clarify the relationship between the injection-site impact and the efficacy of cell therapy. MI was created by coronary ligation in female rats. Three weeks later, 3-million labelled male bone marrow mesenchymal stem cells (BMSCs) were directly injected into the border (BZC group) or central zone (CZC group) of MI area. As a control, culture medium was injected into the same sites. Cell survival was evaluated by quantitative real-time polymerase chain reaction, and apoptosis was assayed with TUNEL and caspase-3 staining. Four weeks after transplantation, heart function and cardiac morphometry were evaluated by echocardiography and Masson's Trichrome staining, respectively. Angiogenesis and myogenesis were detected by immunofluorescence staining. After cell transplantation into the border or central zone, there was no cell migration between the different zones of MI. BMSCs in the CZC group exhibited no difference in apoptotic percentage, in the long-term survival, when compared with those in the BZC group. However, they did effectively promote angiogenesis and cellular myogenic differentiation. Although cell delivery in the central zone of MI had no effect on the recovery of heart function compared with the BZC group, the retained BMSCs could still increase the scar thickness, and subsequently exhibit a trend in the reverse remodelling of ventricular dilation. Hence, we concluded that the central zone of MI should not be ignored during cell-based therapy. Multiple site injection (border+central zone) is strongly recommended during the procedure of cell transplantation.
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