Prevention of acute graft-versus-host disease by magnetic nanoparticles of Fe₃O₄ combined with cyclosporin A in murine models

Abstract

Objective: To investigate the effect of magnetic nanoparticles (MNPs) of Fe(3)O(4) combined with cyclosporin A (CsA) on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in murine models.

Methods: BALB/c mice preconditioned with total-body irradiation generated aGVHD and then were followed with allo-HSCT from allogeneic C57BL/6. Recipient mice were randomly divided into five groups and then given different supportive care and followed up. The physical signs and median survival time (MST) were recorded, peripheral blood cell counts were assessed, and histological changes of the main tissues were evaluated with hematoxylin-eosin staining. Furthermore, fluorescence polarization immunoassay was used to monitor the concentration of CsA.

Results: The irradiated-only mice developed typical aGVHD, and the typical signs of aGVHD in the skin, liver, and intestine were observed by histopathological examination. Both CsA alone and in combination with Fe(3)O(4) MNPs significantly prolonged the MST of recipient mice compared with both the control and the Fe(3)O(4) MNPs groups. Notably, a combination of CsA with Fe(3)O(4) MNPs can elevate the peripheral white blood cells and alleviate the symptoms of GVHD and the pathological damage after allo-HSCT. In addition, the concentration of CsA was higher in plasma, heart, liver, and spleen of recipient mice with supporting care of the combination of CsA with Fe(3)O(4) MNPs than with CsA alone.

Conclusion: Taken together, Fe(3)O(4) MNPs may be used as a carrier of immunosuppressive agents to alleviate GVHD after allo-HSCT in murine models.

Keywords: HSCT; allogenetic stem cell transplantation; mice.

Figure 1

Survival curve of mice after prevention of aGVHD program. Notes: ^a,b<0.05, compared with the irradiation-only group; ^a<0.05, compared to other groups. Abbreviations: aGVHD, acute graft-versus-host disease; MST, medium survival time; CsA, cyclosporine A; Fe₃O₄ MNPs, Fe₃O₄ magnetic nanoparticles.

Figure 2

Body weights of mice for 25 days after irradiation with or without translation. Abbreviations: CsA, cyclosporine A; Fe₃O₄ MNPs, Fe₃O₄ magnetic nanoparticles.

Figure 3

Peripheral white blood cell counts in recipient mice. Abbreviations: CsA, cyclosporine A; Fe₃O₄ MNPs, Fe₃O₄ magnetic nanoparticles.

Figure 4

Histopathology of skin tissues of mice after allo-HSCT [hematoxylin and eosin, magnification ×4 (objective lens)]. (A) Control group; (B) irradiation-only group; (C) Fe₃O₄ MNPs-treated group; (D) CsA-treated group; (E) CsA + Fe₃O₄ MNPs-treated group. Abbreviations: allo-HSCT, allogenetic hematopoietic stem cell transplantation; CsA, cyclosporine A; Fe₃O₄ MNPs, Fe₃O₄. magnetic nanoparticles.

Figure 5

Histopathology of liver tissues of mice after allo-HSCT [hematoxylin and eosin, magnification ×4 (objective lens)]. (A) Control group; (B) irradiation-only group; (C) Fe₃O₄ MNPs-treated group; (D) CsA-treated group; (E) CsA + Fe₃O₄ MNPs-treated group. Abbreviations: allo-HSCT, allogenetic hematopoietic stem cell transplantation; CsA, cyclosporine A; Fe₃O₄ MNPs, Fe₃O₄ magnetic nanoparticles.

Figure 6

Histopathology of intestine tissues of mice after allo-HSCT [hematoxylin and eosin, magnification ×4 (objective lens)]. (A) Control group; (B) irradiation-only group; (C) Fe₃O₄ MNPs-treated group; (D) CsA-treated group; (E) CsA + Fe₃O₄ MNPs-treated group. Abbreviations: allo-HSCT, allogenetic hematopoietic stem cell transplantation; CsA, cyclosporine A; Fe₃O₄ MNPs, Fe₃O₄ magnetic nanoparticles.