Introduction: Cell-based regenerative therapies hold promise in providing treatment strategies for heart failure. Previous work from our laboratory has shown that tissue engineered cardiac constructs enhance improvements in cardiac function by providing structural and nutrient support, potentially aiding in transplanted cell survival, integration and re-population of injured tissues. Our current studies focus on the development and testing of second-generation cardiac constructs utilizing high purity human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs).
Methods: High purity hiPSC-CMs were seeded and co-cultured onto a vicryl matrix embedded with biologically active human dermal fibroblasts. The hiPSC-CM constructs were maintained at 37°C and 5% CO2. Patches were constructed maintained as described for both in vitro and in vivo evaluation. Patches for in vivo evaluation were seeded, cultured and implanted onto the rat heart 3 weeks after left coronary artery ligation to assess improvements in LV function. Patches prepared for in vitro evaluation were seeded and cultured 1-10 days.
Results: Patches constructed with hiPSC-CMs displayed synchronized and spontaneous contractions within 48hrs of culture which developed in robustness over time. At maximal robustness, contractions were visualized across the full thickness of the construct. Contractions were recorded at 36+5 beats BPM. In addition hiPSC-CM constructs respond to electrical stimulation with increased rate of contraction while maintaining their synchrony. Post pacing, the hiPSC-CM constructs return to their intrinsic rhythm.
Conclusion: These findings show that high purity hiPSC-CMs can be seeded and co-cultured onto a vicryl and fibroblast construct in manner permitting adhesion and electromechanical coupling of the hiPSC-CMs to form a fully contractile construct. This is supported by the observation that the hiPSC-CMs contract spontaneously and in a synchronized manner in a directional fashion.