The effect of human cord blood therapy on the intestinal tract of lethally irradiated mice: Possible use for mass casualties

Abstract

Purpose: To evaluate the recovery of the gastrointestinal tract in lethally irradiated mice treated with human cord blood and antibiotics.

Materials and methods: A/J mice were randomly assigned to seven study groups, including groups exposed to acute 9 Gy from ¹³⁷Cs γ-rays to the whole body. Four hours after irradiation, exposed mice were treated with either cord blood nucleated cells, Levaquin, or a combination of both. Weight gain/loss and survival were monitored for 2 months. Upon death or euthanasia, the organs were prepared for molecular and histological analyses.

Results: Whereas irradiated mice (n = 9) lived 6–15 days, ∼ 60% of irradiated mice that received the combined treatment (n = 7) survived more than 50 days. None of the treated animals developed Graft versus Host disease. All animals lost weight after irradiation; however, the 50⁺ days-survivors (n = 4) gained on average ∼1.8 g over their initial weight. Whereas hemorrhagic bone marrow and large areas of transmural necrosis were observed in the bowel of the irradiated mice, the 50⁺ days-survivors showed recovery of the bone marrow. They behaved normally and had significant but incomplete recovery of the intestinal and colonic mucosa. Human DNA was detected in their organs, particularly in the large intestine.

Conclusion: Red cell-depleted cord blood transfusions combined with antibiotic treatment contribute to bone marrow and gastrointestinal recovery in high dose-irradiated mice, and may be an available therapy for mass casualties during radiological emergencies.

Keywords:

• Ionising radiation
• human umbilical cord blood
• stem cells
• intestinal tract
• bone marrow
• mass casualties

Acknowledgements

We wish to thank Dr Kenneth Klein for his consultation on the intestinal tract lesions, Lynn Baltimore and Philip Petrucelli for assistance in manuscript preparation, and Dr David Lagunoff and Peter Carroll for histological preparations. The Abraham S. Ende Research Foundation supported this investigation. EIA is supported by NASA grant NNJ06HD91G.

This paper is in memoriam to the late Dr Milton Ende, who with his brother Dr Norman Ende conducted the first reported successful temporary transplantation of human umbilical cord blood in a patient with leukemia. We also acknowledge the contributions of his staff, and collaborators at the South Side Regional Medical Center, Petersburg, VA (physicians and staff) and the Blood Bank at Grady Memorial Hospital, Atlanta, GA.

Declaration of interest: M.K. is an employee of Celgene Cellular Therapeutics and may have a potential conflict of interest; the other authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.