Mesenchymal stromal cell-conditioned medium prevents radiation-induced small intestine injury in mice

Cytotherapy. 2012 Mar;14(3):267-73. doi: 10.3109/14653249.2011.616194. Epub 2011 Sep 29.

Abstract

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.

MeSH terms

  • Abdomen / radiation effects
  • Adipogenesis
  • Animals
  • Body Weight
  • Cell Hypoxia
  • Cell Survival
  • Culture Media, Conditioned / metabolism*
  • Diarrhea / pathology
  • Diarrhea / therapy
  • Injections, Intravenous
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / radiation effects
  • Intestine, Small / pathology
  • Intestine, Small / radiation effects*
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Weight
  • Osteogenesis
  • Primary Cell Culture
  • Radiation Injuries, Experimental / metabolism
  • Radiation Injuries, Experimental / pathology
  • Radiation Injuries, Experimental / therapy*
  • Rats
  • Survival Analysis
  • Ultrafiltration
  • Umbilical Cord / cytology

Substances

  • Culture Media, Conditioned