Use of MSCs and MSC-Educated Macrophages to Mitigate Hematopoietic Acute Radiation Syndrome

Innovative and minimally toxic treatment approaches are sorely needed for the prevention and treatment of hematopoietic acute radiation syndrome (H-ARS). Cell therapies have been increasingly studied for their potential use as countermeasures for accidental and intentional ionizing radiation exposures which can lead to fatal ARS. Mesenchymal stem/stromal cells (MSCs) are used in cell therapy that have shown promising results in preclinical studies of ARS and are being developed in clinical trials specifically for H-ARS. MSCs, MSC-educated macrophages (MEMs), and MSC-exosome–educated macrophages (EEMs) all have the potential to be used as adoptive cell therapies for H-ARS. Here, we review how MSCs have been reported to mitigate inflammation from radiation injury while also stimulating hematopoiesis during ARS. We discuss emerging work with immune cell subsets educated by MSCs, including MEMs and EEMs, in promoting hematopoiesis in xenogeneic models of ARS. We also discuss the first placental-derived MSC product to enter phase I trials, PLX-R18, and the challenges faced by bringing MSC and other cell therapies into the clinic for treating ARS. Although MSCs, MEMs, and EEMs are potential cell therapy candidates in promoting hematopoietic HRS, challenges persist in translational clinical development of these products to the clinic. Whether any of these cellular therapies will be sufficient as stand-alone therapies to mitigate H-ARS or if they will be a bridging therapy that insures survival until a curative allogeneic hematopoietic stem cell transplant can be performed are the key questions that will have to be answered.