Transplantation of Mesenchymal Stem Cells to Prevent Radiation-induced Intestinal Injury in Mice

Abstract

Mesenchymal stem cells/Transplantation/Embryonic stem cells/Radiation/Intestinal injury.The effective treatments of radiation-induced intestinal injury are currently unavailable. Developing new treatments for radiation-induced intestinal injury is thus important. The present study investigated whether transplantation of mesenchymal stem cells (MSCs) is able to prevent radiation-induced intestinal injury. Intestines of female nude mice (ICR nu/nu) were irradiated at a single dose of 30 Gy. Transplantation of male MSCs (C57BL/6) was then immediately performed into the walls of irradiated intestine by direct injection for the irradiation + MSCs group. Mice were weighed daily and survival was recorded for 13 days after irradiation. From 13 to 27 days after irradiation, intestines of mice were obtained in order to assay histological changes by staining with hematoxylin-eosin and Masson trichrome. Mean body weight of the irradiation + MSC group was significantly higher than that of the irradiation-only group from 8 days after irradiation. In addition, survival rates were significantly higher in the irradiation + MSC group than for the irradiation-only group from 5 days after irradiation. Histological observation revealed that intestines of irradiation + MSC-transplanted mice were thick in the submucosal and muscle layers, and had almost fully recovered from radiation-induced intestinal injury at day 27. Specifically, ulcerated areas in the intestines of the irradiation + MSC-transplanted mice were smaller by 13 days after irradiation and were fewer in numbers at 27 days when compared with the irradiation-only group. Our results suggest that transplanted MSCs may play an important role in preventing radiation-induced injury and may offer a novel method to treat radiation-induced intestinal injury.

Adipose mesenchymal stromal cells minimize and repair radiation-induced oral mucositis

“…MSCs have been applied for the repair of arthritis [63], cardiac muscle [152,153], lung tissue [150], diabetes [154], skin [81,83,155,156], skeletal tissue [157], and digestive tract tissue [87,148,158]. …”

“…When MSCs were given before irradiation, treated mice showed higher body weight, thicker intestinal submucosal and muscle layer, significant higher survival rates and stromal derived factor-1 (SDF-1) expression, and lower numbers of radiation-induced ulcers [158,161]. Another study reported that MSCs therapy showed better maintenance of epithelial homeostasis, neovascularization, high antiinflammatory IL-10, increased expression of VEGF, b-FGF and EGF in irradiated intestine, and increased the homing of CD31-positive hematopoietic stem cells or hematopoietic progenitor cells to the irradiated intestine [70].…”

“…MSCs in measurable numbers at the intestinal injury site [87,158,163]. There were increased levels of IL-10, VEGF, b-FGF, and EGF.…”

Intestinal stem cells and celiac disease

“…A third potential source of ISCs is represented by circulating multipotent SCs of BM origin that can colonize the intestinal epithelium and contribute to its turnover and regeneration [41][42][43] . BM stem cells may participate in gut repair by giving rise to ISCs through direct differentiation and also by providing supporting elements within the ISC niche, as demonstrated in different experimental models [44][45][46][47] . However, the reduced levels of engraftment and the low rate of differentiation into intestinal cells reported in most of these studies discouraged the practical application of these cells in a clinical setting.…”

New insights for pelvic radiation disease treatment: Multipotent stromal cell is a promise mainstay treatment for the restoration of abdominopelvic severe chronic damages induced by radiotherapy

“…After abdominal irradiation, MSCs have the capacity to engraft into the enteric mucosa [14][15][16][17][18] . MSCs are able to repair radiation-induced intestinal damage by inhibiting ulceration [19][20][21] . Mitigation of radiation-induced lethal intestinal injury can similarly be achieved by transplantation of bone marrow-derived adipose stromal cells (BMASC).…”