Abstract 16377: Persistence of Highly Purified Murine Induced Pluripotent Stem Cell Derived Cardiomyocytes after Intramyocardial Injection into Syngeneic Mouse Hearts is Increased by Co-Transplantation of Non-Cardiomyocytes
Purpose: Embryonic or induced pluripotent stem cells can differentiate into functional cardiomyocytes (ES- or iPS-CM) which integrate into host myocardium and improve function of failing hearts as cardiac cell replacement therapy. While highly purified ES- or iPS-CM are needed to avoid teratogenic risk, this therapy’s effectiveness is limited by their poor persistence after transplantation which might be due to their purity. Thus, we tested the co-transplantation of non-CM to improve persistence.
Methods: Male iPS-CM were derived from transgenic murine iPS and highly purified using an antibiotic resistance under a cardiac-specific promoter. In syngeneic female wild-type mice, intramyocardial injection (CTx) of 300,000 iPS-CM with or without 300,000 male wild-type murine embryonic fibroblasts (+MEF) or 300,000 male wild-type murine adult mesenchymal bone marrow cells (+MSC) was performed (each n≥4). Hearts were harvested immediately (0h) or after 24h or 7 days and the number of transplanted cells was determined by quantitative real-time PCR with primers specific for SRY or transgene. Each surgery day, one cell aliquot was mixed with an explanted native heart ex vivo as control (=100%).
Results: Immediately after CTx of iPS-CM alone, 28.4±4.0% of transplanted iPS-CM were detected in recipient hearts and the number decreased to 0.6±0.2% at 24h (p<.001), confirming previous results for ES-CM. After co-transplantation with non-CM the number of detectable male cells (iPS-CM+non-CM) tended to be higher at 24h and further increased over time without difference between +MEF (24h: 2.7±1.5%, 7d: 12.3±5.2%) and +MSC (24: 2.9±1.3%, 7d: 6.1±2.0%, p<.05 over time for both). The number of detectable transgenic cells (iPS-CM) was also higher than in iPS-CM alone at 24h with 1.3±0.7% (+MEF) and 1.5±0.2% (+MSC, p<.05 vs. iPS-CM alone), but at 7d it was unchanged in +MEF (2.4±0.9%) and tended to decrease in +MSC (0.7±0.4%, p=.1).
Conclusions: Similarly to ES-CM, highly purified iPS-CM showed a low engraftment and a poor persistence of <1% at 24h after CTx. Although co-transplantation of non-CM (MEF or MSC) enhanced this value 2-fold and should thus be further investigated, selective proliferation of transplanted non-CM seen at 7d after CTx must be cautiously monitored.
- © 2012 by American Heart Association, Inc.