Genetically Engineered Mesenchymal Stem Cells for Cell and Gene Therapy

Stem cells have enormous potential for regenerative medicine to treat fatal diseases and injuries that cannot otherwise be healed. In particular, adult stem cell-based therapies have been studied for several decades. Mesenchymal stem cells/marrow stromal cells (MSCs) have shown safety and therapeutic efficacy in preclinical models of various diseases such as cardiovascular disease, cancer, bone defects, renal failure, and neurodegenerative disorders. In spite of the great potential, several factors including low survival rate, low efficiency of MSC homing to injured sites, and poor levels of engraftment and retention have been major technical challenges to be overcome before MSC-based therapy can be applied to clinical applications in a consistently therapeutic manner. Genetically modified MSCs can be one option to overcome some of these problems and to deliver therapeutic agents. MSCs are powerful delivery vehicles and potent protein synthesis factories, and therefore the use of gene-modified MSCs to provide growth factors and other signals to improve the repair of damaged or diseased tissues holds much promise. Here we review the basic biology of human MSCs and the current status of preclinical and clinical trials using genetically engineered MSCs.