CBE Seminar - Brad Berron

William J. Bryan Associate Professor, Department of Chemical Engineering, University of Kentucky

Cellular Coatings for Isolation and Implantation of Therapeutic Cells

Abstract

Significant advances have been made in stem cell therapies for damaged cartilage, brain tissue and heart tissue, where modest recovery of function results from paracrine interactions at the site of injection. Still, these therapies have yet to live up to their full potential. The efficacy of stem cell repair of heart tissue is directly correlated with the number of cells injected, and this trend continued up to the maximum obtainable autologous dose. This suggests the benefit to regeneration is dependent on the number of stem cells in the tissue, and that there is a potential for improved functional recovery if more cells are in the injured tissue. Critically in many stem cell therapies, fewer than 5% of the injected stem cells remain at the injection site 24 h after administration; instead these cells are found throughout nonspecific internal organs. Stem cells are typically injected with a buffer to safely lower the viscosity of the injection. Critically, the buffer swells the local tissue with fluid. As this fluid leaves, these rare cells are rinsed away.

Our team recently discovered a naturally degradable, photopolymerized coating technique which temporarily immobilizes cells on targeted surfaces. The cellular coatings are decorated with adhesive ligands which retain the cells at sites of targeted recognition. Further, these 100 nm coatings enable cells to escape over 48 h through the action of biologically-relevant levels of protease enzymes. This pairing of technologies allows active control over cellular retention timescales while not impacting cellular viability and function. Animal studies demonstrate an increase in cell retention in the heart wall at 3 days and a significant improvement in cardiac function at 30 days post infarction with the coated cells over the uncoated cells.

The second portion of this talk will focus on the formation of an interfacial polymer network as a tool to control transport of materials at a mammalian cell membrane. The discussion will be is focused on applications of cellular coatings for the isolation of therapeutic cells. An entirely new approach to cellular sorting will be presented that is based on the selective deposition of a protective coating on a cell and the destruction of all unprotected cells. This new batch process takes less than an hour and is readily scaled up to large batch sizes. Critically, the system is designed for high purity, where all uncoated cells are readily lysed. Purities >95% are common when sorting mixtures of cultured cells and for isolation of cells from whole blood. Multiple modes of protection will be discussed, as will their relationship to mechanical properties and molecular transport across the polymer coating.

Finally, the biomedical research community has aggressively pursued the removal of cells from unmatched hearts and the repopulation of the extracellular matrix with patient derived cells to address the persistent shortage of patient-matched hearts. In these strategies, heart geometry is preserved, immunogenic materials are eliminated, and functional autologous cells are returned to the heart. There are no methods to accurately control the location or density of a given cell population during recellularization, making a full reconstruction of a functioning heart impossible. To solve this problem, we are using binding motifs on the cell surface and on targeted locations in the heart scaffold to specifically load cells at their physiological location.

 

Biography

Dr. Berron is an Associate Professor of Chemical Engineering at the University of Kentucky, and has recently been named the William T. Bryan Professor of Chemical Engineering. His research focuses on polymers and interfacial chemistry, and his work has found a natural fit in the modification of living cell and tissue interfaces. He earned his B.S. in Chemical Engineering from Rose-Hulman Institute of Technology in 2002. He earned his PhD in Chemical Engineering at Vanderbilt University under the direction of G. Kane Jennings in 2008. His research at Vanderbilt on surface modification of electrode surfaces was supported by an NSF fellowship in nanoscale materials science and engineering. Dr. Berron was a postdoctoral researcher at the University of Colorado-Boulder for 3 years where he researched diagnostic assay development in the lab of Christopher N. Bowman. During this time, he earned a position in an NIH training program in pediatric pulmonary disease, where he developed new polymerization mechanisms and approaches appropriate for application in novel diagnostic assays. Following his appointment at UK in the Department of Chemical and Materials Engineering, Dr. Berron was recognized with an NSF CAREER award in the area of biological separations and with a Doctoral New Investigator Award in the field of Surface Science by the American Chemical Society. He has also been awarded an R01 grant from the NIH for his work in cellular coatings.