再生医学ジャーナル

Dedifferentiated Adipocytes Improve Heart Function Post-Myocardial Infarction

Eric J Tsang, Maria C Jordan, Kenneth P Roos, Jessica M Gluck, Medet Jumabay, Kristina I Boström, Richard J Shemin and Sepideh Heydarkhan-Hagvall

Background:The development of pluripotent stem cell-based strategies for regenerative medicine offers hope of one day having a limitless source of therapeutic cells for the repairing of damaged cardiac tissue resulting from myocardial infarction (MI). Dedifferentiated adipose cells (DFAT) have recently gained attention in this regard for their in vitro and in vivo ability to express vascular and cardiac-specific markers. To date, there is limited knowledge with respect to their capacity to improve cardiac function and contractility when introduced into the myocardium after the onset of MI. To that end, this study investigated the in vivo potential of intramyocardially injected mouse DFAT (mDFAT) cells to differentiate towards cardiovascular lineages and enhance cardiac function in a murine model of MI.
Methods: Mature adipocytes were harvested from GFP-transgenic mice and dedifferentiated in vitro to produce pluripotent mDFAT cells. Mice that underwent LAD ligation surgery were injected intramyocardially with a dose of therapeutic mDFAT cells (n=6) shortly after the confirmation of successful MI.
Results: Consistent with previous findings by the authors, we observed an immunofluorescent stain pattern in the infarct area of mDFAT cells adjacent to or co-localized with Troponin T, Cx-43, CD31, isolectin B4 and α-SMA up to eight weeks after cell transplantation. Furthermore, echocardiography and hemodynamic catheterization measurements indicated an overall improvement in global cardiac function, including ejection fraction, fractional shortening and contractility.
Conclusions: This study is the first to report that the transplantation of mDFAT cells into a murine model of MI can preserve cardiac function up to eight weeks after the onset of infarction, suggesting a potential role for DFAT cells as a therapeutic pluripotent cell source in cardiovascular tissue repair.