Casting Doubt on the Safety of “Off-the-shelf” Mesenchymal Stem Cells for Cell Therapy

Abstract

Mesenchymal stem cells (MSCs) show promise for gene delivery to treat various diseases such as anemia and stroke, as well as other oncological and neural disorders.1,2 In this issue of Molecular Therapy, Campeau et al.3 report on an experimental model that compares the responses of allogeneic and syngeneic hosts to the transfer of erythropoietin (EPO)-expressing MSCs. The studies were based on the premise that EPO could be delivered using genetically modified MSCs to treat anemia or myocardial infarction. The treatment of anemia with expanded autologous MSCs seems plausible, in that the chronic nature of anemia is compatible with the time needed to expand bone marrow−derived MSCs to sufficient numbers. However, in the case of acute disorders such as myocardial infarction and stroke,4,5 gene delivery interventions would have to be immediate, thereby eliminating autologous gene-modified MSCs as an option. Because MSCs have been reported to suppress allogeneic responses, in particular graft-versus-host disease,6,7,8 “off-the-shelf” sources of such cells have been proposed to treat various clinical disorders that require intervention at early time points.