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 Fe₃O₄ 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 Fe₃O₄ MNPs significantly prolonged the MST of recipient mice compared with both the control and the Fe₃O₄ MNPs groups. Notably, a combination of CsA with Fe₃O₄ 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 Fe₃O₄ MNPs than with CsA alone.

Conclusion

Taken together, Fe₃O₄ MNPs may be used as a carrier of immunosuppressive agents to alleviate GVHD after allo-HSCT in murine models.

Keywords:

• allogenetic stem cell transplantation
• mice
• HSCT

Acknowledgments

This work was supported by 973 National Key Fundamental Research Project of China (No 2006 CB933205), National Nature Science Foundation of People’s Republic of China (No 30740062 and No 30872970), and Special-Purpose Science Research Foundation for High School (No 20070286042).

Disclosures

The authors have no conflicts of interest to report in this work.