Reply to Zhang and Hei: Mesenchymal Stem Cell–derived Exosomes: Are They Another Therapeutic Method for Extracorporeal Membrane Oxygenation–supported Acute Respiratory Distress Syndrome?

Abstract

We thank Zhang and Hei for their insightful comments on our study of mesenchymal stromal cells (MSCs) in a sheep model of extracorporeal membrane oxygenation and acute respiratory distress syndrome (ARDS) (1). Their principal thesis is that the adverse interaction that we observed, between MSCs and the membrane oxygenator, may be overcome by substituting MSCs with MSCderived exosomes. This proposal has merit. The MSC secretome has been of interest as a therapeutic for some time, particularly MSCderived extracellular vesicles (2), MSC-derived exosomes (3), and MSC-conditioned media (4). These each offer several theoretical advantages over conventional MSC therapy. First, contents of the secretome do not express major histocompatibility complex antigens, removing concerns about immunogenicity. Second, components of the secretome are, in general, easier to store and less susceptible to the adverse effects of storage on efficacy. Third, components of the MSC secretome are much smaller than the cells from which they are derived and thus less likely to be subject to “trapping” in the pulmonary circulation (5). Recently, an early phase trial of an MSCderived exosome treatment for severe coronavirus disease (COVID19) has been reported with no apparent safety issues (6). However, there are some unresolved issues that should be borne in mind.