ArticleBlood2025
Inflammasome-resistant IPSC-derived myeloid-derived suppressor cells ameliorate xenogeneic graft-versus-host disease.
Article in Blood, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Early high-resolution immune profiles are associated with survival, relapse and graft-versus-host-disease after allogeneic hematopoietic cell transplantation.Bone marrow transplantation · 2026Article
- Infused PMN-MDSCs from G-CSF-mobilized PBSCs protect against II-IV° acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.BMC immunology · 2026Article
- Paeoniflorin prevents acute graft-versus-host disease while preserving graft-versus-tumor effects.Frontiers in immunology · 2026Article
- Myeloid-Derived Suppressor Cells: Immunoregulatory Roles and Therapeutic Prospects in Immune-Mediated Hematological Disorders.Journal of immunology research · 2026Review
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29 authors.
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Abstract
abstractFront-line pharmaceutical interventions for treating acute graft-versus-host disease (GVHD) are not uniformly effective and have toxic side effects. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with potent in vitro and in vivo immunosuppressive functions. Clinical translation of in vitro-generated MDSCs has been limited because of requirements for multiple, high infusion doses, the relatively low yield from peripheral blood-sourced MDSCs (PB-MDSCs), and inconsistent product quality. To circumvent these obstacles, we developed a methodology to generate MDSCs using human induced pluripotent stem cell (iPSC)-derived CD34+ cells. Compared with PB-MDSCs, iPSC-derived MDSCs (iMDSCs) shared similar morphology, phenotype, and suppressive function. We found that the CD14+ iMDSC subset possessed the highest suppressor function. In previous studies, we reported that MDSCs transferred into mice with GVHD lost suppressor function because of inflammasome activation and immature myeloid cell maturation. In striking contrast to human PB-MDSCs, we show herein that iMDSCs retained 95% of suppressor function in vitro despite exposure to lipopolysaccharide (LPS) plus adenosine triphosphate (ATP), which are stimuli that activate the inflammasome via danger-associated molecular patterns released during early posttransplant conditioning and GVHD-induced injury. In an in vivo xenogenic GVHD model with PB mononuclear cells, iMDSCs significantly increased recipient survival without loss of antileukemia effects. iMDSC RNA sequencing and gene knockdown studies revealed that the maintenance of the purine metabolizing enzyme, phosphoglycerate dehydrogenase, during LPS plus ATP treatment, was linked to iMDSC inflammasome resistance. Taken together, these findings provide a platform for translating in vitro-generated, off-the-shelf iMDSCs into the clinic for suppressing a spectrum of adverse immune responses, including GVHD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.