Robust T-tubulation and maturation of cardiomyocytes using tissue-engineered epicardial mimetics

Complex three-dimensional (3-D) heart structure is an important determinant of cardiac electrical and mechanical function. In this study, we set to develop a versatile tissue-engineered system that can promote important aspects of cardiac functional maturation and reproduce variations in myofiber directions present in native ventricular epicardium. We cultured neonatal rat cardiomyocytes within a 3-D hydrogel environment using microfabricated elastomeric molds with hexagonal posts. By varying individual post orientations along the directions derived from diffusion tensor magnetic resonance imaging (DTMRI) maps of human ventricle, we created large (2.5 × 2.5 cm²) 3-D cardiac tissue patches with cardiomyocyte alignment that replicated human epicardial fiber orientations. After 3 weeks of culture, the advanced structural and functional maturation of the engineered 3-D cardiac tissues compared to age-matched 2-D monolayers was evident from: 1) the presence of dense, aligned and electromechanically-coupled cardiomyocytes, quiescent fibroblasts, and interspersed capillary-like structures, 2) action potential propagation with near-adult conduction velocity and directional dependence on local cardiomyocyte orientation, and 3) robust formation of T-tubules aligned with Z-disks, co-localization of L-type Ca²⁺ channels and ryanodine receptors, and accelerated Ca²⁺ transient kinetics. This biomimetic tissue-engineered platform can enable systematic in vitro studies of cardiac structure–function relationships and promote the development of advanced tissue engineering strategies for cardiac repair and regeneration.     

Retroperitoneal aspergilloma

We report a previously healthy 8-year-old boy who presented to the hospital with a palpable abdominal mass, fever and abdominal pain. CT and MRI scans confirmed a large mass that was centered in the retroperitoneum. The lesion was biopsied and the histology showed branching hyphae. Tissue cultures grew Aspergillus fumigatus and a diagnosis of aspergilloma was made. The immunological work-up did not reveal an immunodeficiency. This case is a unique presentation of aspergilloma presenting in an unusual location and in an immunocompetent patient.