(3j) Angiogenic and Immuno-Suppressive Scaffold for Cell Transplantation with Magnetic Resonance and X-Ray Imaging of Graft Viability

Background. Currently, I am an instructor with a joint appointment in the Institute for Cell Engineering and the Department of Radiology at the Johns Hopkins University School of Medicine with Dr. Jeff W.M. Bulte as my supervisor. My postdoctoral work focuses on pancreatic beta islet cell engraftment. Here, beta islet cells are encapsulated inside biocompatible hydrogel microcapsules that prevent the opsonization of host antibodies and the subsequent destruction of the graft by the host immune system. The microcapsules are trackable by MRI, X-ray/CT and ultrasonography for image-guided cell transplantation in real-time, and non-invasive imaging of the graft distribution in vivo. I obtained my doctoral degree from the Department of Chemical and Biomolecular Engineering at the University of Notre Dame under the guidance of Dr. Andre F. Palmer. In my graduate research, I synthesized artificial red blood cells using surface-engineered liposomes and polymeric vesicles for blood substitute applications and treatment of anemia. Applying a combination of my backgrounds, I would like to pursue a research in tissue engineering and therapeutic agent delivery with medical imaging capabilities to guide, study and monitor the efficacy of treatment in vivo.

Angiogenic and Immuno-suppressive Scaffold to Support Cell Transplantation.  Transplantation of organ or cells holds great potential to treat and cure various diseases, such as diabetes, liver failure, stroke and heart disorders. Cell transplantation in humans, however, has been hampered by severe immune rejection, potential toxicity of immunosuppressive drugs used to suppress the immune responses, insufficient cell graft revascularization, and the lack of ability to monitor the fate of graft post-transplantation. Furthermore, grafts should survive the initial hypoxic condition following engraftment and eventually connect with the host vasculature system in order to have a therapeutic benefit. My target disease is type I diabetes and engraftment of pancreatic beta islet cells is currently the most promising therapy to treat this disorder. Here, I propose to design and develop a scaffold system to promote vascularization of the graft, and provide anti- inflammatory and immuno-suppressive properties without the use of drugs. My biomaterial of choice for the scaffold is a biodegradable and anti-inflammatory hydrogel that has tunable physical properties and encourages integration of the graft into host tissues. Supportive stem cells will be co-encapsulated inside the scaffold to promote intra- and extra-islet cell vascularization. Unlike previous cell encapsulating scaffolds that rely on co-encapsulated growth factors and immuno-suppressive agents, these supportive cells 1) produce a steady supply of growth factors in vivo to support the formation and the subsequent maturation of blood vessels, 2) support the graft during the initial hypoxia following transplantation, and 3) modulate the host immune responses by secreting immuno-suppressive factors.

Non-Invasive Monitoring and Quantification of Graft Viability Using Magnetic Resonance Imaging and X-ray Computed Tomography. Prior to encapsulation into scaffold, cell grafts will be labeled with bioinert perfluorocarbon (PFC) nano-emulsions for monitoring of the grafts using magnetic resonance imaging (MRI) and/or X-ray computed tomography (CT). Non-viable cells release their PFC agents, which are subsequently removed by the body. The mass of viable cell graft correlates with the signals of MRI and CT. Therefore, this strategy offers a non-invasive method to monitor and quantify the graft survival over time, and is particularly beneficial in clinical cases.

Drug Delivery Vehicles with Imaging Capabilities. I am also interested to explore the applications of PFC nano-emulsions as drug delivery vehicles that can be tracked by MR-, CT- and/or ultrasound imaging. Drugs and other therapeutic compounds can be loaded inside PFC emulsions. The surface of the emulsions can be engineered to target specific in vivo sites or cells. Using PFC, the delivery and in vivo distribution of therapeutic agents can be guided, serially tracked and/or quantified by clinical medical imagers.