Ferroptosis Susceptibility in Pediatric Immune Thrombocytopenia: Alteration in Mesenchymal Stromal Cells
- 1Department of Woman, Child and General and Specialist Surgery, University of Campania “Luigi Vanvitelli”, 80138 Napoli, Italy
- 2Department of Haematology, Bambino Gesù Hospital, 00165 Rome, Italy
- 3Department of Life Science, Health and Health Professions, Link Campus University, 00165 Rome, Italy
Abstract
Immune thrombocytopenia (ITP) is the most common pediatric thrombocytopenia, characterized by immune-mediated platelet destruction and altered inflammatory responses. Among these alterations, mesenchymal stromal cells (MSCs) from ITP patients display reduced viability and impaired immunoregulatory functions. Our previous work revealed dysregulated iron metabolism in ITP-MSCs, with increased intracellular iron accumulation driven by hepcidin–FPN1 axis disruption and overexpression of iron importers. Given the link between iron overload, oxidative stress, and ferroptosis, a regulated iron-dependent form of cell death, we investigated whether ITP-MSCs exhibit oxidative and molecular alterations associated with ferroptosis. ITP-MSCs showed increased ROS levels and ACSL4 expression, together with reduced expression of proteins involved in ferroptosis-related antioxidant defense, including SLC3A2, SLC7A11, and GPX4. Increased extracellular release of HMGB1, a DAMP associated with cellular stress and different forms of regulated cell death, was also observed. Treatment with Ferrostatin-1 (Fer-1) and Deferasirox (DFX) reduced oxidative stress and partially restored the expression of ferroptosis-related markers. Similarly, high-dose dexamethasone (HD-Dexa) reduced ROS and ACSL4 levels and limited extracellular HMGB1 release. Collectively, these findings support increased susceptibility to ferroptotic stress in ITP-MSCs and reveal a ferroptosis-associated oxidative stress phenotype with concomitant alterations in ferroptosis-related molecular pathways. Moreover, the effects of HD-Dexa, DFX, and Fer-1 suggest that modulation of these pathways may represent a potential strategy for limiting oxidative cellular damage in ITP-MSCs.
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BibTeX
@article{feo2026ferroptosis,
title = {{Ferroptosis Susceptibility in Pediatric Immune Thrombocytopenia: Alteration in Mesenchymal Stromal Cells}},
author = {Giuseppe Di Feo and Maria Maddalena Marrapodi and Oriana Di Domenico and Lucia Argenziano and Michele La Manna and Elisabetta Lembo and Giuseppe Palumbo and Francesca Rossi and Alessandra Di Paola},
journal = {International journal of molecular sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27198917},
url = {https://europepmc.org/article/PMC/PMC13665037},
note = {CC BY},
}
RIS
TY - JOUR
TI - Ferroptosis Susceptibility in Pediatric Immune Thrombocytopenia: Alteration in Mesenchymal Stromal Cells
AU - Giuseppe Di Feo
AU - Maria Maddalena Marrapodi
AU - Oriana Di Domenico
AU - Lucia Argenziano
AU - Michele La Manna
AU - Elisabetta Lembo
AU - Giuseppe Palumbo
AU - Francesca Rossi
AU - Alessandra Di Paola
PY - 2026
DA - 2026/10/01
JO - International journal of molecular sciences
DO - 10.3390/ijms27198917
UR - https://europepmc.org/article/PMC/PMC13665037
AB - Immune thrombocytopenia (ITP) is the most common pediatric thrombocytopenia, characterized by immune-mediated platelet destruction and altered inflammatory responses. Among these alterations, mesenchymal stromal cells (MSCs) from ITP patients display reduced viability and impaired immunoregulatory functions. Our previous work revealed dysregulated iron metabolism in ITP-MSCs, with increased intracellular iron accumulation driven by hepcidin–FPN1 axis disruption and overexpression of iron importers. Given the link between iron overload, oxidative stress, and ferroptosis, a regulated iron-dependent form of cell death, we investigated whether ITP-MSCs exhibit oxidative and molecular alterations associated with ferroptosis. ITP-MSCs showed increased ROS levels and ACSL4 expression, together with reduced expression of proteins involved in ferroptosis-related antioxidant defense, including SLC3A2, SLC7A11, and GPX4. Increased extracellular release of HMGB1, a DAMP associated with cellular stress and different forms of regulated cell death, was also observed. Treatment with Ferrostatin-1 (Fer-1) and Deferasirox (DFX) reduced oxidative stress and partially restored the expression of ferroptosis-related markers. Similarly, high-dose dexamethasone (HD-Dexa) reduced ROS and ACSL4 levels and limited extracellular HMGB1 release. Collectively, these findings support increased susceptibility to ferroptotic stress in ITP-MSCs and reveal a ferroptosis-associated oxidative stress phenotype with concomitant alterations in ferroptosis-related molecular pathways. Moreover, the effects of HD-Dexa, DFX, and Fer-1 suggest that modulation of these pathways may represent a potential strategy for limiting oxidative cellular damage in ITP-MSCs.
SN - 1422-0067
ER -