Abstract 11204: Emulating the Cardiac Mechanical and Humoral Cues to Prolong Human Heart Slice Culture

• DOI: 10.1161/circ.144.suppl_1.11204
• Publication Date: 2022-03-19T23:58:21Z
• Authors: Moustafa Meki; Jessica Miller; Qinghui Ou; Ahmad Gebreil; AbouBakr Salama; Xianliang Tang; Riham Abouleisa; Ayman S El-Baz; Guruprasad Giridh...; Tamer Mohamed
• Keywords: 03 medical and health sciences; 0302 clinical medicine; 3. Good health

Introduction: Drug induced cardiotoxicity is a major cause of market withdrawal. The limited availability human heart tissue has led to inaccurate interpretations cardiac related drug effects. Our group had developed culture system for pig/human slices that functionally and structurally viable 6 days under electric stimulation enriched media could reliably demonstrate the subacute toxic effect anti-cancer therapeutics. However, by day 10, underwent cardiomyocyte dedifferentiation fibrotic remodeling, making them inadequate long-term testing. Aims: Including physiological mechanical humoral cues within can prolong viability in culture. Methods Results: Following small molecule screening, we found incorporation 100 nM Tri-iodo-thyronine (T3) 1 μM Dexamethasone (Dex) into our preserved microscopic structure 12 pig slices. RNA sequencing revealed significant down regulation contractile genes as early 8 To address this, novel bioengineered Cardiac Tissue Culture Model (CTCM) electro-mechanically stimulate with preload afterload during each cycle (Figure 1). Transcriptionally, combining CTCM T3/Dex treatment, was able maintain gene expression at same levels fresh hear tissue. Functionally, cultured completely structural metabolic activity days. Conclusion: This study demonstrates new provides maintaining functionality may be an ideal platform chronic