Effects of transplanted bone marrow mesenchymal stem cells on the irradiated intestine of mice

Abstract

We investigated the potency of exogenous bone marrow mesenchymal stem cells (MSCs) to engraft into irradiated intestine, as well as these cells' effects on radiation-induced enteric injury. MSCs from beta-Gal-transgenic mice were transplanted into C57BL/6J recipient mice that received abdominal irradiation (13 Gy). At different time points, recipient intestines were examined for the engraftment of donor-derived cells by immunofluorescence analysis. Additionally, the expression status of chemokines induced by radiation injury was analyzed in the irradiated intestine. Next, MSCs were transduced with an adenoviral vector encoding a certain chemokine receptor gene in order to promote the engraftment rate via chemotaxis. The intestinal permeability and histomorphological alterations were measured to evaluate the therapeutic effect of MSC transplantation. The results demonstrated that infused MSCs possessed the potency to engraft into irradiated enteric mucosa, but the engraftment rate was too low to produce a therapeutic effect. The expression of stromal cell-derived factor-1 (SDF-1) was up-regulated in irradiated intestine. MSCs genetically modified by CXCR4 (the receptor for SDF-1) engrafted into irradiated intestine at a significantly elevated level and ameliorated the intestinal permeability and histopathological damage.