Iron Overload Results in Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation By Impairing Hematopoiesis

Background:

Clinical data suggest that pre-transplant iron overload due to high transfusion requirements may affect graft function after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .

OBJECTIVE:

To determine the impact of iron overload and its underlying mechanism on poor graft function (PGF) .

METHODS:

In the setting of allo-HSCT, a BALB/C mice and a C57/BL6 (H-2b) were used as recipient and donor, respectively. Recipient mice were injected intraperitoneally with iron sucrose with the cumulative doses of 50 mg, 100 mg, and 200 mg in three experimental groups, while the control with phosphate-buffered saline. All mice received total body irradiation for HSCT. Plasma iron levels and Iron stores of liver, spleen and bone marrow (BM) were measured. Hematological parameter, CD34+ cells and the hematopoietic colony-forming capacity were monitored to evaluate the hematopoietic recovery. Bone marrow derived mesenchymal stem cells (BM-MSCs) were isolated and assessed for proliferation. Immunohistochemical analysis assessed the BM microenvironment, expression of haematopoietic chemokines and immunological parameters.

RESULTS:

Iron overload aggravated PGF as observed by the results that peripheral blood cells were significantly lower in number and recovered less rapidly with a dose-dependend manner, compared with that of controls (P<0.05). In the experimental groups, BM was hypocellular, CD34+ cell counts and colony-forming units were significantly decreased (P<0.05). BM-MSCs showed a longer double time than control (P<0.05). Furthermore, the immunohistochemical analysis demonstrated the immunological impairment and the low expression of stem cell factor -1 and vascular endothelial growth factor-1.

CONCLUSION:

Current evidence shows that iron overload is an important risk factor for PGF by damaging hematopoietic stem cells and the microenvironment, which highlights the need for optimizing iron management to improve the transplantation outcomes.