Establishing a Platform for in Vivo Functional and Structural Assessment of Composite Tissue Allotransplants with Quantitative Magnetic Resonance and Optical Imaging

Overcoming rejection is the main obstacle of composite tissue allotransplant. The ability to monitor the transplanted graft long-term is vital for the research of rejection process and associated tolerance induction methods. The traditional observation methods, biopsy and blood sampling, are flawed with sampling bias and a lack of dynamic real time inspection; and more importantly, they are both invasive. Biopsy and blood sampling methods are “destructive detections” because that the immunity or cell movement might be affected by the wound and the correctness of the research might be affected consequently. On this account, the development of an in vivo imaging platform for long-term monitoring is urgently needed. The in vivo imaging platform is not only important for the research of mechanisms, but also facilitates the screening of therapies for overcoming rejection; it will provide valuable information for both academic research and clinical application, translating from the bench to bedside. Three specific aims are proposed: I. Establish the platform with tissomic validation for the in vivo monitoring of the rejection after CTA. A. Activated macrophage B. Cell injury C. Blood vessel and blood flow D -1. Representative molecules of the acute rejection -2. Representative molecules of the chronic rejection E. Chimerism II. Assess the effectiveness of adipose-derived stem cell (ADSC)-induced immune tolerance with the in vivo imaging platform. III. Assess the effectiveness of Regulatory T cells (Treg)-induced immune tolerance with the in vivo imaging platform. In this project, optical imaging, magnetic resonance imaging (MRI), and ultrasound imaging will be used in combination to establish a platform for the long-term in vivo monitoring of rejection and immune tolerance in CTA rat models. To confirm the effectiveness and accuracy of this platform, in vitro validation will be completed with objective, accurate and reproducible “tissomic” cellular quantitativeanalysis from the new technology “Tissomics Analyzer/TissueGnostics TissueFAXS PlusTM”. Furthermore, the cellular factors related to rejection and immune tolerance will be multiple-stained and quantitative cross-analyzed for further elucidation of related molecular and cellular mechanisms. Our research team has achieved initial success in developing the therapies with ADSCand Treg-induced immune tolerance. These therapeutic modalities will be further investigated with the in vivo imaging platform. In addition, completion of this project will help us to understand the mechanisms of how ADSC and Treg induce immune tolerance and will provide beneficial information for future clinical applications.

Project ID:PC10107-0360
External Project ID:NSC101-2314-B182-016