IMAGING-AIDED GENE THERAPY USING MESENCHYMAL STEM CELLS AS TARGET-DELIVERY VEHICLE

摘要

Compositions and methods of use thereof encompass engineered mesenchymal stem cells as a vehicle to deliver secreted tissue necrosis factor-RGD4C fusion polypeptides for tumor treatment, thereby reducing side effects of TNF. A reporter gene can be included in vector constructs to monitor the localization and viability of engineered MSCs after administration into a recipient animal. The genetically modified mesenchymal stem cell can comprise an expression cassette comprising a nucleic acid sequence operably linked to a gene expression promoter and encoding the heterologous fusion polypeptide comprising a tissue necrotic factor region and an integrin-binding region. Another aspect of the disclosure encompasses embodiments of a method of modulating the proliferation of a targeted population of tumor cells by delivering a population of the genetically modified mesenchymal stem cells to tumor cells, allowing the mesenchymal stem cells to express the heterologous polypeptide, thereby reducing the proliferative capacity of the tumor cells.