the antidiabetic effect of mscs is not impaired by insulin prophylaxis and is not improved by a second dose of cellsmsc的抗糖尿病的作用不受胰岛素预防和不提高了第二个剂量的细胞.pdfVIP

The Antidiabetic Effect of MSCs Is Not Impaired by Insulin Prophylaxis and Is Not Improved by a Second Dose of Cells Fernando Ezquer, Marcelo Ezquer, Valeska Simon, Paulette Conget* Instituto de Ciencias, Facultad de Medicina, Clinica Alemana Universidad del Desarrollo, Santiago, Chile Abstract Type 1 diabetes mellitus (T1D) is due to autoimmune destruction of pancreatic beta-cells. Previously, we have shown that intravenously administered bone marrow-derived multipotent mesenchymal stromal cells (MSCs) allows pancreatic islet recovery, improves insulin secretion and reverts hyperglycemia in low doses streptozotocin (STZ)-induced diabetic mice. Here we evaluate whether insulin prophylaxis and the administration of a second dose of cells affect the antidiabetic therapeutic effect of MSC transplantation. Insulitis and subsequent elimination of pancreatic beta-cells was promoted in C57BL/6 mice by the injection of 40 mg/kg/day STZ for five days. Twenty-four days later, diabetic mice were distributed into experimental groups according to if they received or not insulin and/or one or two doses of healthy donor-derived MSCs. Three and half months later: glycemia, pancreatic islets number, insulinemia, glycated hemoglobin level and glucose tolerance were determined in animals that did not received exogenous insulin for the last 1.5 months. Also, we characterized MSCs isolated from mice healthy or diabetic. The therapeutic effect of MSC transplantation was observed in diabetic mice that received or not insulin prophylaxis. Improvements were similar irrespective if they received one or two doses of cells. Compared to MSCs from healthy mice, MSCs from diabetic mice had the same proliferation and adipogenic potentials, but were less abundant, with altered immunophenotype and no osteogenic potential.