I am a second year PhD student developing a stem cell based therapy for the treatment of heart failure. My research aims to address the major limitations in the field of cardiac cell therapy, namely the relative immaturity of pluripotent stem cell derived cardiomyocytes (PSC-CMs) in addition to their poor retention following administration to the infarcted heart. Biomaterials have the potential to address these issues however identifying suitable biomaterials with characteristics similar to those of the human heart has proven challenging.
Through the BHF regenerative medicine centre a number of fruitful collaborations have been essential in the development of this project. The lab of Prof. Ipsita Roy has previously generated various Polyhydroxyalkanoates (PHAs), a family of biomaterials produced by bacteria under growth-limited conditions. These biomaterials are mechanically conducive to cardiac tissue engineering and have been shown to be highly bioresorbable with controllable degradation kinetics resulting in the production of non-toxic degradation products.
As such, the initial phase of my PhD involved me conducting numerous bacterial fermentations to generate various PHAs. These were subsequently characterised to determine their mechanical, structural and thermal properties. Following this, I travelled to the Karolinska Institute in Sweden where I spent a month within the lab of Prof. Molly Stevens working on melt electrospinning writing (MEW), a fabrication technique capable of generating reproducible, fibrous 3D scaffolds. PSC-CMs and pluripotent stem cell derived endothelial cells (PSC-ECs) were then generated and seeded upon these MEW scaffolds with subsequent imaging experiments revealing a propensity for the PSC-CMs to adopt an elongated morphology complete with a defined sarcomeric architecture when situated on the scaffold. Current studies are investigating whether this structural enhancement translates to functional maturation of the PSC-CMs.
More recently, working alongside Dr. Gabor Foldes, we have developed conditions for the co-culture of PSC-CMs and PSC-ECs and are currently attempting to scale up the production of pluripotent stem cell derived endothelial cells (PSC-ECs). Additionally, physical and pharmacological mechanisms to improve the long-term stability of these cells are also being studied.
As we continue to develop our biomaterial based stem cell patch, initial in-vivo studies are being conducted in conjunction with Mr Matthew Delahaye and Dr. Catherine Mansfield to determine the degradation kinetics of PHAs in this scaffold configuration in addition to their immunogenicity. In the coming months I am aiming to complete the characterisation of our patch before beginning to determine the functional effects it has on our rat model of myocardial infarction.