Evaluation of stem cell administration in a model of kidney ischemia-reperfusion injury

Abstract

Ischemia-reperfusion injury is a common early event in kidney transplantation and contributes to a delay in organ function. Acute tubular necrosis, impaired kidney function and organ leukocyte infiltration are the major findings. the therapeutic potential of stem cells has been the focus of recent research as these cells possess capabilities such as self-renewal, multipotent differentiation and aid in regeneration after organ injury. FTY720 is a new synthetic compound that has been associated with preferential migration of blood lymphocytes to peripheral lymph nodes instead of inflammatory sites. Bone marrow stem cells (BMSC) and/or FTY720 were used as therapy to promote recovery of tubule cells and avoid inflammation at the renal site, respectively. Mice were submitted to renal ischemia-reperfusion injury and were either treated with two doses of FTY720, 10 x 10(6) BMSC, or both in order to compare the therapeutic effect with non-treated and control animals. Renal function and structure were investigated as were cell numbers in peripheral blood and spleen. Activation and apoptosis markers were also evaluated in splenocytes using flow cytometry. We found that the combined therapy (FTY720+BMSC) was associated with more significant changes in renal function and structure after ischemia-reperfusion injury when compared with the other groups. Also a decrease at cell numbers and prevention of spleen cells activation and apoptosis was observed. in conclusion, in our model it was not possible to demonstrate the potential of stem cells alone or in combination with FTY720 to promote early kidney recovery after ischemia reperfusion injury. (c) 2007 Elsevier B.V. All rights reserved.