Abstract
BackgroundEffective therapeutic strategies to address intestinal complications after radiation exposure are currently lacking. Mesenchymal stem cells (MSCs), which display the ability to repair the injured intestine, have been considered as delivery vehicles for repair genes. In this study, we evaluated the therapeutic effect of hepatocyte growth factor (HGF)-gene-modified MSCs on radiation-induced intestinal injury (RIII).MethodsFemale 6- to 8-week-old mice were radiated locally at the abdomen with a single 13-Gy dose of radiation and then treated with saline control, Ad-HGF or Ad-Null-modified MSCs therapy. The transient engraftment of human MSCs was detected via real-time PCR and immunostaining. The therapeutic effects of non- and HGF-modified MSCs were evaluated via FACS to determine the lymphocyte immunophenotypes; via ELISA to measure cytokine expression; via immunostaining to determine tight junction protein expression; via PCNA staining to examine intestinal epithelial cell proliferation; and via TUNEL staining to detect intestinal epithelial cell apoptosis.ResultsThe histopathological recovery of the radiation-injured intestine was significantly enhanced following non- or HGF-modified MSCs treatment. Importantly, the radiation-induced immunophenotypic disorders of the mesenteric lymph nodes and Peyer’s patches were attenuated in both MSCs-treated groups. Treatment with HGF-modified MSCs reduced the expression and secretion of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ), increased the expression of the anti-inflammatory cytokine IL-10 and the tight junction protein ZO-1, and promoted the proliferation and reduced the apoptosis of intestinal epithelial cells.ConclusionsTreatment of RIII with HGF-gene-modified MSCs reduces local inflammation and promotes the recovery of small intestinal histopathology in a mouse model. These findings might provide an effective therapeutic strategy for RIII.
Highlights
Radiation exposure may occur due to a nuclear accident or radiotherapy
The therapeutic effects of non- and hepatocyte growth factor (HGF)-modified Mesenchymal stem cells (MSCs) were evaluated via FACS to determine the lymphocyte immunophenotypes; via enzyme-linked immunosorbent assay (ELISA) to measure cytokine expression; via immunostaining to determine tight junction protein expression; via PCNA staining to examine intestinal epithelial cell proliferation; and via TUNEL staining to detect intestinal epithelial cell apoptosis
Several experimental and clinical studies have reported the therapeutic effects of MSCs in alleviating gastrointestinal disorders in patients with severe steroid-resistant graft-versus-host disease (GVHD), and the recovery of rectovaginal and perianal fistulas in patients with Crohn’s disease [7, 8]
Summary
Radiation exposure may occur due to a nuclear accident or radiotherapy. The development of novel approaches that protect living tissues from radiation-induced damage is an important field in radiation biology. Several experimental and clinical studies have reported the therapeutic effects of MSCs in alleviating gastrointestinal disorders in patients with severe steroid-resistant graft-versus-host disease (GVHD), and the recovery of rectovaginal and perianal fistulas in patients with Crohn’s disease [7, 8]. Immunomodulatory activities, such as the suppression of T-cell proliferation and the distribution of MSCs in inflamed tissue, are considered as the central mechanisms of action of MSCs [9, 10]. We evaluated the therapeutic effect of hepatocyte growth factor (HGF)-gene-modified MSCs on radiation-induced intestinal injury (RIII)
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