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Updated: Apr 16, 2026
Author Spotlight: Analyzing Bone Marrow Microenvironment in Murine Hematological Malignancies
Published on: November 10, 2023
RETRACTED: Effects of iron overload on the bone marrow microenvironment in mice
Yuchen Zhang1, Wenjing Zhai2, Mingfeng Zhao1
1Department of Hematology, Tianjin First Central Hospital, Tianjin, China.
Objective:
Using a mouse model, Iron Overload (IO) induced bone marrow microenvironment injury was investigated, focusing on the involvement of reactive oxygen species (ROS).
Methods:
Mice were intraperitoneally injected with iron dextran (12.5, 25, or 50 mg) every three days for two, four, and six week durations. Deferasirox(DFX)125 mg/ml and N-acetyl-L-cysteine (NAC) 40 mM were co-administered. Then, bone marrow derived mesenchymal stem cells (BM-MSCs) were isolated and assessed for proliferation and differentiation ability, as well as related gene changes. Immunohistochemical analysis assessed the expression of haematopoietic chemokines. Supporting functions of BM-MSCs were studied by co-culture system.
Results:
In IO condition (25 mg/ml for 4 weeks), BM-MSCs exhibited proliferation deficiencies and unbalanced osteogenic/adipogenic differentiation. The IO BM-MSCs showed a longer double time (2.07±0.14 days) than control (1.03±0.07 days) (P<0.05). The immunohistochemical analysis demonstrated that chemokine stromal cell-derived factor-1, stem cell factor -1, and vascular endothelial growth factor-1 expression were decreased. The co-cultured system demonstrated that bone marrow mononuclear cells (BMMNCs) co-cultured with IO BM-MSCs had decreased colony forming unit (CFU) count (p<0.01), which indicates IO could lead to decreased hematopoietic supporting functions of BM-MSCs. This effect was associated with elevated phosphatidylinositol 3 kinase (PI3K) and reduced of Forkhead box protein O3 (FOXO3) mRNA expression, which could induce the generation of ROS. Results also demonstrated that NAC or DFX treatment could partially attenuate cell injury and inhibit signaling pathway striggered by IO.
Conclusion:
These results demonstrated that IO can impair the bone marrow microenvironment, including the quantity and quality of BM-MSCs.
Insights
Iron overload (IO) injures the bone marrow microenvironment, impairing mesenchymal stem cells (BM-MSCs) and hematopoietic support. Treatments like N-acetyl-L-cysteine (NAC) and Deferasirox (DFX) partially mitigated these negative effects.
Area of Science:
- Hematology
- Stem Cell Biology
- Toxicology
Background:
- Iron overload (IO) is a condition associated with excessive iron accumulation.
- The bone marrow microenvironment is crucial for hematopoiesis and stem cell function.
- Reactive oxygen species (ROS) are implicated in cellular damage and disease pathogenesis.
Purpose of the Study:
- To investigate the impact of iron overload (IO) on the bone marrow microenvironment in a mouse model.
- To elucidate the role of reactive oxygen species (ROS) in IO-induced bone marrow injury.
- To evaluate the therapeutic potential of Deferasirox (DFX) and N-acetyl-L-cysteine (NAC) in mitigating IO effects.
Main Methods:
- Mice were subjected to iron dextran injections to induce iron overload.
- Bone marrow-derived mesenchymal stem cells (BM-MSCs) were isolated and assessed for proliferation, differentiation, and gene expression.
- Immunohistochemistry, co-culture systems, and molecular analyses (PI3K, FOXO3) were employed to evaluate BM-MSC function and signaling pathways.
Main Results:
- Iron overload (IO) significantly impaired BM-MSC proliferation and induced unbalanced osteogenic/adipogenic differentiation.
- IO led to decreased expression of hematopoietic chemokines (SDF-1, SCF, VEGF) and reduced hematopoietic supporting functions of BM-MSCs.
- Elevated PI3K and reduced FOXO3 mRNA expression were observed in IO conditions, correlating with increased ROS generation; NAC and DFX treatments showed partial protective effects.
Conclusions:
- Iron overload (IO) demonstrably impairs the bone marrow microenvironment.
- The quantity and quality of bone marrow-derived mesenchymal stem cells (BM-MSCs) are negatively affected by IO.
- ROS play a significant role in mediating IO-induced bone marrow microenvironment damage.
