McGowan Institute for Regenerative Medicine affiliated faculty member Shilpa Sant, PhD, was named one of eleven of the 2017 Young Innovators of Cellular and Molecular Bioengineering (CMBE) and her work is featured in the October 2017 issue of the journal. As a 2017 CMBE Young Innovator, Dr. Sant will present her research in a special, two-part invited platform session at the 2017 Annual Meeting of BMES in Phoenix, Arizona.
Dr. Sant is an Assistant Professor in Pharmaceutical Sciences, with a secondary appointment in Bioengineering. Research in her lab focuses on developing physiologically relevant in vitro disease models and developing novel therapies to combat these diseases.
In the 2017 CMBE Young Innovator issue, Dr. Sant, along with Pitt Pharmacy graduate student, Yingfei Xue, and collaborators report their work on reactive oxygen species (ROS)-modulating shape-specific cerium oxide nanoparticles (CNPs) as a therapeutic strategy to inhibit oxidative stress-induced heart valve calcification. Indeed, elevated levels of reactive oxygen species in valve tissue have been identified as a prominent hallmark and driving factor for valvular calcification, which still remains a significant clinical challenge without effective pharmacological treatments. To address this, Dr. Sant and colleagues developed an oxidative stress-induced valve calcification model using valve interstitial cells (hVICs) isolated from two patients with stenotic valves and a healthy donor. They demonstrated that hVICs derived from calcified valves exhibited impaired antioxidant defense mechanisms and were more susceptible to oxidative stress than normal hVICs. They further demonstrated therapeutic effect of ROS-modulating shape-specific cerium oxide nanoparticles (CNPs) to inhibit oxidative stress-induced valvular calcification. CNPs are a class of self-regenerative ROS-modulating agents, which can switch between Ce3+ and Ce4+ in response to the surrounding oxidative microenvironment.
Other Pitt co-authors of this work include Cynthia St. Hilaire, PhD, and Luis Hortells, DVM, PhD (Cardiology & Vascular Medicine Institute); McGowan Institute for Regenerative Medicine affiliated faculty member Julie Phillippi, PhD (Cardiothoracic Surgery); and Vinayak Sant, PhD (Pharmaceutical Sciences). Read the full research article here.
Building on this work, Dr. Sant and co-authors envision to create a three-dimensional valve calcification model using human cells so that it can be further extended for testing potential therapies. They also envision that self-regenerative cerium oxide nanoparticles will be a useful platform to balance ROS for many other diseases where excessive oxidative stress is implicated in disease progression.
Cellular and Molecular Bioengineering, an official journal of the Biomedical Engineering Society (BMES), publishes research that advances the study and control of mechanical, chemical, and electrical processes of the cell. Each year, the editors of CMBE dedicate the Young Innovators special issue to highlighting the work of assistant professors conducting innovative bioengineering research at the molecular, cellular, and multi-cellular level.
Paper (Shape-specific nanoceria mitigate oxidative stress-induced calcification in primary human valvular interstitial cell culture. Yingfei Xue, Cynthia St. Hilaire, Luis Hortells, Julie A. Phillippi, Vinayak Sant, Shilpa Sant. Cellular and Molecular Bioengineering; October 2017, Volume 10, Issue 5, pp 483–500.)