Engineering THP-1 Cells to Enable Longitudinal Reporter Gene Imaging to Assess Decellularized Adipose Tissue Hydrogels as a Delivery Platform for Human Monocytic Cells
Abstract
Cell-based therapies using biomaterial scaffolds for localized injection of pro-regenerative cells offer a promising approach for vascular regeneration in peripheral artery disease. The objective of this project was to evaluate decellularized adipose tissue (DAT) hydrogels as an injectable delivery vehicle to enhance the localized retention of monocytes, using the THP-1 monocytic cell line as a surrogate for human monocytes. The THP-1 cells were engineered to co-express the red fluorescence reporter gene dTomato, the bioluminescence imaging (BLI) reporter gene firefly luciferase 2, and the magnetic resonance imaging reporter gene organic anion transporting polypeptide 1B3 to longitudinally track viable cell retention within the DAT hydrogels. In vitro BLI confirmed THP-1 cell persistence in DAT hydrogels over 11 days. Additionally, BLI demonstrated retention and survival of THP-1 cells following intramuscular injection in NOD/SCID mice within the DAT hydrogels compared to saline delivery controls, highlighting the potential of DAT hydrogels for localized monocyte delivery.