The Effects of Co-injecting Human iPSC-Derived Cardiomyocytes/Pre-epicardial Cells into Cryoinjured Rat Hearts

Objectives: Previously, pre-epicardial cells derived from human-induced pluripotent stem cells successfully recapitulated important developmental effects, including the induction of cardiomyocyte proliferation and compaction in vitro.In this study, we tested the use of pre-epicardial cells (PECs) in cardiomyocyte (CM) therapy for cryoinjured rat hearts. Materials and methods:Adult male Sprague Dawley rats (250-300g) were administered cyclosporin 3 days prior to surgery.All rats were intubated and underwent thoracotomy under general anaesthesia.Hearts were cryoinjured using a liquid nitrogen-cooled vanadium cryoprobe twice, with 30 seconds for each application.After 10 minutes, CMs (1×106) were injected perpendicularly into the affected ventricular area, towards the infarct border region, both with and without PECs (1×106).Shamoperated and untreated groups (PBS-treated) served as controls.Cardiac haemodynamics were measured using the Millar Pressure Volume System after 4 weeks.Differences between groups were determined using ANOVA and considered significant when p<0.05. Results:The preliminary results showed that cryoinjury reduced the left ventricular ejection fraction to 48.2 ± 4.6% (n=5), compared to 77.7 ± 4.8% in the sham group (n=4, p=0.0065).CM and CM/PEC treatment improved the LVEF to 57.85 ± 5.8% and 57.5 ± 4.1% (n=6), respectively, but the difference was not significant compared to the untreated group after 4 weeks.Resting end-systolic elastance (Ees), which measures load-independent cardiac contractility, was improved in the CM-treated group (0.8 ± 0.4 mmHg/ml versus 0.3 ± 0.1 mmHg/ml in the untreated group, p=0.01).No significant difference was observed between the CM and CM/PEC groups. Conclusion:Further in-depth assessments are required to examine the effects of pre-epicardial cells in cardiomyocyte therapy in vivo.