Mesenchymal Stem Cell as Targeted-Delivery Vehicle in Breast Cancer

摘要

Mesenchymal stem cells (MSCs) have been proposed to be cellular vehicles for the targeted delivery and local production of biological agents in tumors. In this proposal we will stably transfect mesenchymal stem cells with a lentiviral vector containing a therapeutic gene and dual reporter gene mrfp- ttk. Specific Aims: 1) We will monitor breast cancer tropism of mesenchymal stem cells by multimodality imaging techniques; 2) We will demonstrate the ability of mesenchymal stem cells to target delivery of gene therapeutics to breast cancer in vitro; 3) We will determine the effect of mesenchymal stem cell to target delivery of gene therapeutics to breast cancer lung metastasis. Major findings from year 1 studies: 1) MSCs home to both subcutaneous breast cancer and its lung metastasis; 2) MSCs home to both premature and well- established breast cancer lung metastasis; 3) MSCs proliferate at tumor site; 4) MSCs show dissimilar differentiation potential at lung tumor and subcutaneous tumor niches; 5) lung tumor microenvironment upregulates BMP-2 and Noggin transcription, which favor MSCs osteoblastogenic differentiation.