Optical Fluorescence Imaging-based Real-time Monitoring of Myocardial Tissue Regeneration

Abstract

Real-time longitudinal monitoring of living cells provides an insight in understanding the mechanism of cellular migration from the transplanted graft and its integration with that of the host tissues. Different kinds of imaging modalities using nontoxic and stable contrast agents have been explored to quantify the presence of cellular migrations from the graft to the host tissues. However, longitudinal monitoring of cells is currently limited by the lack of a stable probe in the near-infrared (NIR) window. In addition, difficulties related to the use of multimodal channels limit its application in real-time tracking of multiple cells in vivo , thereby demanding for an alternate approach to combat the existing challenges. The present work demonstrated long-term simultaneous tracking of multiple cells in vivo using 3 charge-coupled device (3CCD) optical fluorescence imaging technique and different types of stable, nontoxic and target-specific fluorescent dyes in the NIR window. To do so, a cell-laden patch using tissue derived extracellular matrix (dECM) encapsulated with endothelial cells was fabricated via 3D bioprinting technique and implanted at the site of myocardial infarction (MI) in a rat MI model. Furthermore, the multimodal 3CCD optical fluorescence imaging based system was employed to differentiate between healthy and ischemic zone using different contrast agents and track the cellular migration from implanted graft to host tissue. Thus, the developed imaging system having high sensitivity and multimodal capability offers a platform to longitudinally monitor living cells in vivo , which is pivotal for understanding biological mechanisms such as cell migration, integration and neovascularization.