Core A: Ultrastructural Assessment & Human Tissue

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SUMMARY/ABSTRACT – Scientific Core - Structure The goal of the Ultrastructural Assessment and Human Tissue Core is to maximize the scientific progress and productivity of the PPG investigators by providing essential services. The primary function of Core A is to serve human and porcine myocardial and stellate ganglion tissue needs across all projects and Core B. Given significant regulatory and logistical hurdles needed to procure and study human heart and stellate ganglion tissues, it is ideal for this to be handled by a central core. The core will perform three key functions for the study: 1) tissue clearing and ultrastructural imaging; 2) procurement of normal (or near normal) and diseased human tissues, specifically hearts and stellate ganglia; and 3) molecular biology. All 3 projects of this PPG with utilize at least two of these services, and there will be tight links between this core and Core B, the Functional Assessment and Instrumentation Core. Over the past 15 months, we have built a pipeline to obtain diseased hearts from patients undergoing orthotopic heart transplantation, and normal or near normal hearts rejected for organ transplant. Our infrastructure for obtained stellate ganglia from patients with cardiomyopathy undergoing stellectomy, and stellate ganglia from patients without cardiopulmonary disease at the time of heart and/or lung donation has existed for 5 years. Given the unpredictable times at which these tissues become available, centralizing the tissue procurement activities within this core will benefit the PPG by streamlining protocols and approvals, minimizing cost, and boosting productivity. The Core will also streamline the 4-week process of tissue clearing from pigs and humans by batching tissues to minimize error, tissue clearing involves numerous steps and chemicals. Finally, it is most ideal that tissues are cleared and imaged in high resolution in close coordination with study team members from Projects 1-3 in this Core whether or not the tissues are cleared. For the duration of the PPG, the core is poised – with experience, robust protocols, and experienced personnel – to provide critical services that ensure the success of this PPG.