Labeling of Mesenchymal Stem Cells using Indocyanine Green for Photoacoustic Imaging

Abstract

Stem cell therapies offer great potential for treatment of various diseases and stem cell tracking is a really important subject for clinical applications. Currently, there have been a lot of clinical trials with different kinds of stem cell replacement therapies. Stem cells are quickly developing to regenerating the damaged cardiac tissue and induction to neovascularization. Though, transplanted cells are unknown whether the fate or not. By the observing of the real-time fate of transplanted cells, possible to overcome to this challenge in future. Recently, many methods have been afflicted by limitations such as penetration depth or sensitivity and risk of cytotoxicity of the labeling agents. To be of most useful tracking method should be noninvasive, long-term, selective, sensitive and high resolution abilities to understand mechanisms behind successful therapies. In this study, a vitro experiment was accomplished to demonstrate noninvasive imaging technique with clinically relevant indocyanine green (ICG) which is a safety, cost-effective, and superior labeling technique for imaging and have evidently accepted the effectiveness for clinical studies. PAI system that could visualize transplanted stem cells and further to enhance stem cell delivery techniques, therefore we focused to photoacoustic (PA) signals changes of MSCs labeled with indocyanine green (ICG) at different time points (day 1, 3 and 5, respectively) for real time monitoring of tracking cells. In order to detect PA signals on biological tissues, we utilized a polyvinyl alcohol (PVA) phantom which excluded four compartments to inject MSCs (1 x 106) labeled with ICG (1.0 mg/ml) with different labeling times. As demonstrated by our experiment, there were significantly higher PA signals from mesenchymal stem cells labeled with ICG on day 1 compared to others (day 3 and 5) because of fluorescence gradually decreased that could be influenced PA signal changes. These results revealed the feasibility of using US/PA imaging techniques for longitudinal cell tracking and monitoring for further investigations. Keywords: Indocyanine green, ultrasound and photoacoustic imaging, mesenchymal stem cells, noninvasive photoacoustic imaging, longitudinal cell tracking.