BACKGROUND AIMS: Effective therapy for radiation-induced intestinal injury is currently unavailable. Mesenchymal stromal cells (MSC) are expected to be useful in repairing intestinal damage caused by irradiation. We determined whether the MSC-derived bioactive components could protect radiation-induced small intestine injury in mice. METHODS: Human umbilical cord (UC)-derived MSC were isolated, expanded and exposed to hypoxic conditions in vitro. The hypoxia-conditioned medium was ultrafiltrated with a 3-kDa molecular weight cut-off to prepare the high molecular weight fraction (HMWF). The effect of HMWF on the viability of irradiated rat intestinal epithelial cells (IEC-6) was examined by MTT(methyl thiazolyl tetrazolium) assay. HMWF was also delivered to BALB/C male mice by tail intravenous injection immediately after receiving local abdominal irradiation at a selected dose of 10 Gy. Animal body weight, survival and diarrhea were monitored for 30 days. The improvement of mice intestine structure, including epithelium thickness and villus height, was examined by histology. RESULTS: HMWF enhanced the viability of irradiated IEC-6 cells in vitro. Repeated infusion of HMWF for 7 days immediately after abdominal irradiation of 10 Gy ((60)Coγ-ray) increased the survival rate, decreased diarrhea occurrence and improved the small intestinal structural integrity of irradiated mice. CONCLUSIONS: MSC-derived bioactive components could be a novel therapeutic approach for the treatment of radiation-induced injury.
BACKGROUND AIMS: Effective therapy for radiation-induced intestinal injury is currently unavailable. Mesenchymal stromal cells (MSC) are expected to be useful in repairing intestinal damage caused by irradiation. We determined whether the MSC-derived bioactive components could protect radiation-induced small intestine injury in mice. METHODS:Human umbilical cord (UC)-derived MSC were isolated, expanded and exposed to hypoxic conditions in vitro. The hypoxia-conditioned medium was ultrafiltrated with a 3-kDa molecular weight cut-off to prepare the high molecular weight fraction (HMWF). The effect of HMWF on the viability of irradiated rat intestinal epithelial cells (IEC-6) was examined by MTT(methyl thiazolyl tetrazolium) assay. HMWF was also delivered to BALB/C male mice by tail intravenous injection immediately after receiving local abdominal irradiation at a selected dose of 10 Gy. Animal body weight, survival and diarrhea were monitored for 30 days. The improvement of mice intestine structure, including epithelium thickness and villus height, was examined by histology. RESULTS: HMWF enhanced the viability of irradiated IEC-6 cells in vitro. Repeated infusion of HMWF for 7 days immediately after abdominal irradiation of 10 Gy ((60)Coγ-ray) increased the survival rate, decreased diarrhea occurrence and improved the small intestinal structural integrity of irradiated mice. CONCLUSIONS: MSC-derived bioactive components could be a novel therapeutic approach for the treatment of radiation-induced injury.
Authors: Marc Benderitter; Fabio Caviggioli; Alain Chapel; Robert P Coppes; Chandan Guha; Marco Klinger; Olivier Malard; Fiona Stewart; Radia Tamarat; Peter van Luijk; Charles L Limoli Journal: Antioxid Redox Signal Date: 2014-02-03 Impact factor: 8.401