Science Highlights
Published on September 16, 2025
Developing off-the-shelf human iPSC-derived MDSCs resistant to inflammasome activation for the prevention of GVHD
by Blood
Ma L, Koehn BH, Zaiken MC, et al. Inflammasome-Resistant IPSC-Derived Myeloid-Derived Suppressor Cells Ameliorate Xenogeneic Graft-Versus-Host-Disease. Blood. 2025; (doi: 10.1182/blood.2025028562).
Scientists say myeloid-derived suppressor cells (MDSCs) engineered with human induced pluripotent stem cells (iPSC) may hold the key to migrating off-the-shelf MDSCs to the clinical setting, where they promise to combat graft-versus-host disease (GVHD). Using MDSCs for this purpose has been elusive, in part because a series of infusions is needed to effectively curtail inflammation. Additionally, there must be a high number of suppressor cells compared to T cells; yet peripheral blood samples deliver relatively small yields. MDSCs developed with iPSC-derived CD34+ cells (iMDSCs) exhibited immune-suppressing activity on par with blood-derived versions. However, unlike conventional MDSCs — which are stripped of their suppressive properties as a result of inflammasome activation and immature myeloid cell maturation related to GVHD injury — the iMDSCs preserved 95% of suppressor function. Researchers attribute this resistance against inflammasome effects to the fact that iMDSCs expressed and maintained high levels of phosphoglycerate dehydrogenase — a serine-producing enzyme — in the presence of inflammasome-activating stimuli. When transferred in vivo with peripheral blood MDSCs, the iMDSCs prolonged survival and preserved anti-leukemia effects.
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