Piggy-back heart – a self powered Fontan assist device
Murali Padala, PhD, Emory University
Award Type: Innovation Fund
Abstract: Children surviving with a Fontan circulation lack a pump in their venous circulation, with the venous flow passively flowing into the lungs. A slightly higher pulmonary vascular resistance can impede venous flow, leading to its pooling in the vena cavae. Central venous pressure rises, and that has an adverse impact on the liver and several other organ systems. The need for mechanical devices that can assist the venous circulation in these patients is now established, but appropriate technologies are lacking that can be used in the long-term, without the risk of thrombosis and drive line infections, and do not make the child bed ridden. In this talk, I will introduce our concept of a piggy back heart, which is a self powered implantable chamber to drive Fontan circulation.
Development of a tissue engineered trans-catheter heart valve for use in the endovascular repair of single ventricle cardiac anomalies in utero
Dr Lakshmi Prasad Dasi, Georgia Tech
Award Type: Innovation Fund
Unlocking Our Regenerative Capacity: Elucidating The Role Of LYST On Neotissue Formation In Tissue Engineered Vascular Grafts
Gabriel Mirhaidari, BS, The Abigail Wexner Research Institute at Nationwide Children’s Hospital / The Ohio State University
Award Type: Innovation Fund (Chris Breuer)
Abstract: Tissue engineered vascular grafts (TEVGs) hold great promise for advancing the care of children born with single ventricle defects by providing an autologous vessel that can grow and remodel with the patient. However, TEVG stenosis remains a challenge to clinical translation. Our bench-to-beside and back again approach has focused on utilizing small animal models to better inform the biological mechanisms behind TEVG stenosis and identify potential therapeutic interventions for use in the clinic. We serendipitously discovered that TEVGs have improved performance when implanted in Beige mice, which are defined by a mutant gene encoding lysosomal trafficking regulator (LYST) protein, and were able to reproduce this effect through anti-LYST antibody treatment. As little is known about LYST and its immunomodulation effects, we herein report a series of experiments to further elucidate the role of LYST mediated immunomodulation in TEVG neovessel development. Wild-type (C57BL6/J) mice and Beige mice are implanted with TEVGs. At 2 weeks, mice are imaged utilizing micro-PET CT to determine degree of TEVG stenosis and inflammation. TEVGs are explanted and digested for single cell RNA-sequencing with follow-up hierarchical clustering, heat map and gene ontology and pathway analyses performed. An anti-LYST locked nucleic acid (LNA) siRNA is generated to allow selective silencing of LYST and subsequently its molecular signaling pathways associated with LYST-mediated neovessel formation. An optimized dose of the LNA is administered to mice implanted with TEVGs with follow-up micro-PET CT angiography at 2-weeks to assess TEVG stenosis and inflammation. Grafts are explanted for single-cell RNA sequencing. The incidence of stenosis and inflammation, as well as results from single-cell RNA sequencing pathway analysis, is compared to results from the non LNA treated wild-type and beige mice to inform differences in molecular signaling pathways associated with LYST-mediated neotisue formation and LYST’s role in inhibiting TEVG stenosis.