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

• Published in: International journal of radiation biology 2010-06, Vol.86 (6), p.467-475
• Main Authors: Azzam, Edouard I., Yang, Zhi, Li, Min, Kim, Soyeon, Kovalenko, Olga A., Khorshidi, Manoochehr, Ende, Norman
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; bone marrow; Cord Blood Stem Cell Transplantation; DNA - metabolism; Female; Fetal Blood - transplantation; Gastrointestinal Tract - drug effects; Gastrointestinal Tract - pathology; Gastrointestinal Tract - radiation effects; Gastrointestinal Tract - surgery; human umbilical cord blood; Humans; intestinal tract; Ionising radiation; Levofloxacin; mass casualties; Mass Casualty Incidents; Mice; Ofloxacin - pharmacology; Space life sciences; stem cells; Survival Rate; Time Factors
• ISSN: 0955-3002; 1362-3095
• DOI: 10.3109/09553000903567987

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.