Stem Cell-Based Macrophage Gene Therapy for Atherosclerosis

Peyton Bluhm

Mentor: Dr. Senlin Li

Macrophages are associated with atherogenises due to their involvement in both lipid metabolism and inflammation, which are two critical processes in atherogenesis. Macrophages are known to have certain genes that are anti-atherogenic and others that are pro-atherogenic. By manipulating these genes through over-expression of anti-atherogenic genes and/or knocking down of pro-atherogenic genes, novel strategies for treatments of atherosclerosis may be developed.
Our goal was to generate bone marrow-derived apoE-/- hematopoietic stem cells (HSC) that had been transfected with lentiviral vectors that express therapeutic genes when the HSCs differentiated into macrophages. The HSC that had undergone gene therapy were transplanted into irradiated apoE-/- atherosclerosis model mice to ameliorate the atherosclerosis condition (i.e. reduced plaque formation and size).