Abstract 349: Tracking Human Pluripotent Stem Cell-Derived Cardiomyocytes in Post-Myocardial Infarction Heart with Photoacoustic Imaging

Abstract

Background: Molecular imaging has helped unravel potential benefits and barriers of stem cell therapy, yet in vivo tracking of cell injection and engraftment with high 3D spatial resolution remains a challenge. This study aims to testify the feasibility of photoacoustic imaging (PAI) as an efficient method to monitor transplanted therapeutic cells in post-myocardial infarction (MI) hearts. Methods: Cell penetrating peptide-conjugated photoacoustic nanoparticles (PANPs) were synthesized and applied directly to cultured human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) at the concentration of 4nM for 6h. Post exogenous labeling, cells were injected into mouse MI hearts (n=5) guided by PAI and then monitored by PAI in vivo . These engraftments were further confirmed by immunostaining. Results: Flow cytometry and confocal imaging indicated that PANP labeling significantly increased the labeling efficiency of hPSC-CMs from 38% to 90% compared to endocytosis labeling. Moreover, calcium imaging and contractile analysis indicated that PANP labeling had no cardiotoxicity to both electrical and mechanical functions of hPSC-CMs. In addition, quantitative polymerase chain reaction (qPCR) showed no adverse effects of PANP labeling on the genes related to cardiomyocyte structures and functions. Finally, animal experiments demonstrated the feasibility of PAI for both injection guidance and followed tracking of hPSC-CMs in vivo . The real-time acquired PAI images showed a high spatial resolution (~100 μm) for mice hearts and a high intensity for the labeled cells. Conclusion: We utilized PAI for the first time to monitor cardiac regenerative therapy in a preclinical study. PAI demonstrated its superior potential to track cell therapy in vivo due to its high spatial resolution, low cost, and non-radioactivity. It will be a useful tool for the investigation of cardiac regenerative therapy.