In vivo Evaluation Using Fluorescence Imaging after Transplanting Tissue Constructs Fabricated by 3D Bioprinting Technology

Abstract

Stem cell therapy has been actively studied as a treatment for ischemic heart disease. Particularly, a patch-type carrier can improve the therapeutic effect by enhancing homing and engraftment of stem cells into damaged myocardial tissues. Meanwhile, 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 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 longterm 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. In this study, we are aiming to monitor the efficacy of cardiac stem cell-laden patch in ischemic myocardial tissue by using optical fluorescence imaging based on the NIR probes. First, we used three sets of spectral filter and CCD sensor. Second, contrast agents were selected to observe ischemic tissue, mitochondria, and lipoprotein. Using 3D bioprinting technology, we fabricated a pre-vascularized tissue construct with bioink composed of decellularized extracellular matrix and stem cells. Finally, we observed the interaction between the delivered construct and the ischemic myocardial tissue after transplanting it into the heart of the rats.