Abstract
Some patients who undergo radiotherapy may develop side effects that can be life threatening. Tissue complications can result in functional alterations of organs caused by radiation-induced stem cell depletion. Stem cell therapy is a promising approach to improve radiotherapy-enhanced tissue complications. The multipotential of Mesenchymal Stem Cells (MSC), their easy isolation and high ex vivo expansive capacity make these cells good candidates for replenishment of the depleted stem cell compartment during radiotherapy. In this study, we make the assumption that radiation-induced normal tissue injuries might play a role in the recruitment of MSC for tissue repair. We isolated MSC from the human bone marrow (hMSC) and transplanted them via the systemic route into immunotolerent NOD/SCID mice. Using two models of radiation-induced lesion (total body irradiation: TBI, total abdominal irradiation: TAI), we have studied the link between tissue damage and hMSC implantation. Tissue alterations were studied by histological analysis. hMSC in tissues of transplant was quantified by real-time PCR assay 14 days after their injection. In unirradiated NOD/SCID mice, hMSC homed significantly in lung (0.06% of total lung cells), muscle (0.07%) and bone marrow (0.14%). Following TBI of NOD/SCID mice at a sublethal dose (3.2 Gy), we observed an increase of engraftment in brain (0.07%), heart (0.05%), liver (0.11%), muscle (0.12%) and bone marrow (0.37%) compared to unirradiated mice. TAI (8 Gy) induced a significant increase of hMSC engraftment levels in kidney (0.10%), stomach (0.12%), liver (0.44%), spleen (0.94%), and small intestine (0.17%) compared to TBI mice. Histological study show that MSC reduce radiation-induced intestinal lesion: following AI, MSC accelerate the renewal of small intestine in participating to their regenerative process. From 3 days after radiation exposure, when hMSC are injected, the integrity of small intestine is already regained. The villus length is significantly increased (1.7 fold compared with control). We also observe many proliferating zone). 15 days after irradiation, the villus length remains elevated and is significantly increased in comparison with uninjected or unirradiated group. We then demonstrated that hMSC could accelerate and favour small intestinal regeneration after radiation-induced their damages. We conclude that mainly MSC implantation takes place in radiation-injured organs of exposed areas. We demonstrate the capacity of hMSC to improve the spontaneous renewal of NOD/SCID mice small intestine. The characterization of the capacity of MSC in intestinal functional recover is under progress in our laboratory.
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