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DOI: 10.1055/s-0034-1367202
Site-specific positioning of magnetic nanoparticle (MNP) loaded progenitors improves survival of the grafted cells and long-term myocardial function upon myocardial infarction
Objectives: Recently we could demonstrate, that myocardial cell engraftment was significantly increased if cells prior to transplantation were loaded with MNP and injected under application of a magnetic field. In the present study we have investigated the underlying mechanisms as well as the consequences on the long-term hemodynamic effects.
Methods: EGFP-transgenic murine embryonic cardiomyocytes (eCM, E 13,5 - 15,5) were isolated and incubated overnight with SOMag5 MNPs (200 pg Fe/cell). Then, 200.000 MNP-loaded cells were injected into a myocardial cryolesion while co-applying a magnetic field. Proliferation and apoptosis of transplanted cells was investigated by immunohistochemistry 2,3,6 and 14 days postoperatively, cardiac function was determined by left ventricular catheterization after 2 and 8 weeks.
Results: Overall cell engraftment rates were improved significantly at 2 and 8 weeks after transplantation. Detailed histological as well as immunohistochemical analysis showed a significantly increased initial cell retention rate after magnet-assisted transplantation. Furthermore, caspase3 and Ki67 staining revealed decreased apoptosis and increased proliferation rates of the transplanted cells in the early postoperative phase. This led also to a significant enhancement of short- (14 days) and long-term (2 months) heart function.
Discussion: Thus, MNP-loading of eCM and consecutive magneto-assisted intramyocardial injection strongly improves cell engraftment and results in a long term improvement of hemodynamics. Besides better retentions rates upon application of the cells (less cell loss through the coronary system and the injection channel), also biological mechanisms seem to be involved.