Keratinocyte growth factor enhanced immune reconstitution in murine allogeneic umbilical cord blood cell transplant

Abstract

Umbilical cord blood (UCB) is used increasingly as a source of hematopoietic cells because of a lower risk of graft-versus-host disease (GVHD). Myeloablative conditioning before allogeneic umbilical cord blood transplant (allo-UCBT) results in thymic epithelial cell injury and T-cell immune deficiency. Full-term fetal blood cells were used as hematopoietic cells in a previous murine allo-UCBT model with a limited number of mice surviving the myeloablative conditioning. We designed a viable murine allo-UCBT protocol with platelet concentrate support. Keratinocyte growth factor (KGF) is a mitogen of thymic epithelial cells that promotes recovery of thymic epithelium when given before total body irradiation (TBI)-containing conditioning in experimental murine models. We hypothesized that KGF pre-administration would improve post-allo-UCBT thymopoiesis. To test this hypothesis, allo-UCBT recipient mice were given KGF or control saline prior to UCBT. Platelet concentrate support significantly improved the survival rate of murine allo-UCBT recipients. KGF administration significantly increased donor-derived T and natural killer T (NKT) cells at day +35 in spleens of allo-UCBT recipients. KGF administration also improved thymic function after allo-UCBT, resulting in higher copies of signal joint T-cell receptor rearrangement excision circles (sjTRECs) in splenocytes. Finally, we found that KGF pre-administration could enhance the graft-versus-leukemia effect. In conclusion, KGF can be administered safely to recipients of allo-UCBT to enhance T-cell immune reconstitution.

Keywords:

• Umbilical cord blood transplant
• keratinocyte growth factor
• immune reconstitution
• graft-versus-leukemia
• murine model

Acknowledgements

We thank the staff of Soochow University Animal Facility for animal care. We would like to thank Xiaobo Wang for assistance in collecting murine fetal blood, Sheng Xu for mouse irradiation, and Xiulin Hu for critical reading of the manuscript.

This study was supported by grants SS0718, KF200943 and H200721 from the Suzhou Science and Development Program, grant 20093201110010 from the Ministry of Education of the People's Republic of China, grant LJ200626 from the Scientific Research Foundation of the Health Ministry of China, grant 2009ZX09503 from the National Science and Technology Major Program, and grant Q312203210 for a Suzhou University Young Researcher.

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