#IDIBELLfellows: Laura Casado Medina / Lidia Collado Rodríguez

3D Bioprinted Tubular Cardiac Tissues as a Tool for Cardiac Therapies
Laura Casado Medina  – Stem Cell Potency Group
Heart failure remains a global health concern, necessitating advancements in regenerative strategies. Tubular engineered cardiac tissues (tECTs) integrated into ventricular assist devices could significantly enhance heart failure treatment. This study aims to generate tECTs that closely mimic ventricular wall organization and functionality through innovative tissue engineering techniques. The central layer, emulating the myocardium, is 3D bioprinted to form a tubular construct using an optimized bioink based on gelatin, fibrinogen, hyaluronic acid, and cardiac cells derived from human-induced pluripotent stem cells (hiPSC). Immunohistochemical analysis confirmed the expression of key cardiac markers, with spontaneous contractions observed even 30 days post-bioprinting under all culture conditions. However, when cultured under continuous flow perfusion and mechanical stimulation, the tECTs showed improved stability and cellular organization, better elongation and orientation of cells along the axis of stimulation, and enhanced cell viability due to improved diffusion. Current efforts are also focused on incorporating inner and outer layers, mimicking the endocardium and epicardium, to further enhance structural and functional integrity. This approach effectively mimics the natural ventricular wall composition and organization, representing a crucial step towards physiologically accurate cardiac tissues for therapeutic applications, disease modeling, and drug testing in cardiology.

Regulation of cell death and cytokine secretion by the Integrated Stress Response. Involvement in lung cancer progression
Lidia Collado Rodríguez – Preclinical and Experimental Research in Thoracic Tumors (PReTT) Group
Cells that form solid tumors are frequently stressed due to their high metabolic needs and their exhaustion of nutrients. To deal with this, cells display the Integrated Stress Response (ISR), mediated by phosphorylation of eIF2α and induction of the transcription factor ATF4. This response leads to metabolic rewiring and secretion of cytokines that may contribute to permanent inflammation and immunosuppression. The ISR is initiated by four eIF2α kinases: PERK, GCN2, PKR, and HRI depending on the stimuli. Particularly, PERK is important for ISR activation under glucose deprivation and contributes to tumor growth and immune evasion in mouse models. Here we study how glucose deprivation affects cell proliferation and cell death in human lung cancer cells. We obtained the transcriptome of glucose-deprived A549 cells showing the activation of the ISR upon glucose deprivation in our cells. Then, we investigated how ISR impairment affects cell death and proliferation using different inhibitors. Last, we used free-glucose physiological-like media to check whether our results were replicated in a more physiological environment.