Multiscale Fractal Shape Cues Support Hierarchical Maturation Of Podocytes Via Curvature induced Extracellular Matrix Patterning

Purpose/Objectives: Nature efficiently self-organizes cells and tissues into complex fractal forms. Whether fractal patterning contributes functionally to maturation, and how cells sense and interpret such shape cues, is not well understood. Methodology: Using kidney podocytes as a model system, bioinspired templating of glomerular histology was leveraged to design controlled fractal 21/2 -D surfaces for cell culture. Results: Microcurvature was associated with charge density gradients in space, found to direct extracellular matrix protein organization resulting in hierarchical assembly of cell structures and fractally-branching podocyte morphology in vitro, that was delineated clearly in vitro with a novel highresolution fluorescent assaying technique. Shape stimulation was uniquely associated with development of mature-like foot processes and organized ECM. In applications of drug testing, coronavirus infection, and a cells-as-sensors approach to patient serum diagnostics, fractally stimulated cells were more responsive than flat cultures. Conclusion/Significance: Fractal frameworks may thus provide a functional role in podocyte maturation and could serve to advance other bioengineered systems.

STUDYING CARDIAC SIDE EFFECTS OF SARS-COV-2 INFECTION AND SCREENING EXTRACELLULAR VESICLE THERAPEUTICS IN VITRO

Unlike seasonal coronaviruses, SARS-CoV-2 has a profound tropism for the heart. Estimates indicate 78% of individuals infected with SARS-CoV-2 experience cardiac side effects, with asymptomatic individuals still at risk of viral-induced heart failure, yet the mechanisms and consequences of such effects remain unclear. [1] Thus, therapeutics targeting SARS-CoV-2-induced heart failure remain elusive. The organ-on-a-chip industry has emerged at the intersection of microfluidics and tissue engineering, combining cells and biomaterials in arrangements that mimic organ processes, facilitating investigation of human physiology in a controlled and accessible environment. [2],[3] Recent studies indicate that cell signalling in the heart plays an integral role in tissue physiology and phenotype. [4],[5] For instance, it has been suggested that extracellular vesicles (EVs) released and taken up by cells in the heart are critical to regulating cardiac function and cellular responses to stress, disease, and injury. [6],[7] The “Biowire” model of cardiac tissueon-a-chip was used to study the cardiac side effects of coronavirus infection in the heart and to screen EV therapeutics for mitigating such effects. EVs sourced from induced pluripotent stem cells (iPSCs) facilitated the recovery of infected cardiac tissue function to baseline levels. miRNA sequencing and gene ontology analyses suggested several stress responsive pathways are targeted by iPSCEV miRNA that may alleviate some detrimental effects of coronavirus infection. Limited knowledge regarding SARS-CoV-2 side effects in the heart make tissue-on-a-chip models a novel tool to better understand the mechanisms of viral-induced heart failure and to study the potential for cell signalling-based therapeutics to improve patient outcomes.

Kidney Transplantation in a Recipient with Positive RT-PCR for SARS-CoV-2

When it is safe to proceed with transplantation after coronavirus disease 2019 (COVID-19) infection is still unknown. We describe the clinical course and management of immunosuppression in a patient with positive real-time polymerase chain reaction (RT-PCR) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in a nasopharyngeal swab at the time of kidney transplantation, and with positive antibodies for SARS-CoV-2. The patient had no complications and was discharged with a functioning graft.