Research

Despite many currently available therapeutics to treat heart failure, such as biomimetic scaffolds made of natural or synthetic polymers, their limited mechanical and biodegradable properties, as well as high potential for immunological rejection, are still in question. Direct injection of stem cells or catheter-based intracoronary procedures also reported only modest therapeutic benefits due to poor localized cell survival after injection or lack of supported elements for mature vasculature.  

To improve bio-compatibility and bio-functionality, enhance angiogenesis and facilitate blood vessel maturation, we have been generating stem cell-derived bi-layer cell sheets to treat heart failure progression following myocardial infarction. We hope that the implantation of our unique, spatially oriented bi-layer cell sheet would support the retention of the implanted cells and help form mature vasculature, enhancing the therapeutic effects of the cell sheet technique on ischemic cardiomyopathy (ICM).  

With an aim on clinical translation, we are applying the cell-derived bi-layer cell sheets in a preclinical large animal model of ischemic heart failure. Utilizing cells collected and differentiated in clinically translatable ways, we hope to bridge the gap between basic research and application in human patients for our bio-engineered tissue therapy.

With the invention of the 3D printer, scaffold-based solutions have significantly improved tissue engineering and regenerative medicine. However, these biomaterial-based interventions often entail problems, including imitations in materials used to create scaffolds, immunogenicity triggered by synthetic materials, and scaffold degradation in vivo. Thus, their relatively short lifespan and narrow therapeutic application limit their success as efficient treatments in a clinical setting. 

To overcome such problems, we are combining stem cell biology with the 3D bio-fabrication system to create scaffold-free tissues. These living tissues have low toxicity and high capability to maintain physical and biomechanical properties required for tissue growth long term, augmenting their translatability.

A better understanding of the molecular and genetic basis of myocardial dysfunction has made gene-based therapy a promising treatment alternative for heart failure.  
 
Our laboratory utilizes the latest technologies in next-generation sequencing to analyze the gene expression in the cardiac tissue of the failing heart. In collaboration with the Human Biorepository Tissue Bank for sample collection, we seek to uncover which genes are subject to changes in expression in response to an improvement in blood flow caused by the placement of a ventricular assist device (LVAD). Our virtuous cycle of the bench to bedside to bench again, combining genome sequencing with clinical data and biostatistics, will accelerate insights into the function of genetic variants and signaling pathways that could give rise to therapeutics to improve cardiac function without the need for invasive surgical procedures.  

A left ventricular assist device (LVAD) has emerged as a bridge to transplantation and a viable destination therapy for patients who have reached end-stage heart failure. LVAD implantation still comes with a vast spectrum of long-term complications, particularly confined driveline infections (DLI) affecting the tissues around the driveline outlet.

By using information technology, our laboratory incorporates artificial intelligence (AI) into patient management and DLI detection. We hope to provide patients with an LVAD with a more efficient way to monitor their driveline conditions while decreasing their burden of finding frequent and specialized care. This early intervention will ultimately reduce the incidence of severe DLI and improve patients' lives.