Mesenchymal stem cells prevented the progression of diabetic nephropathy, improved renal function and microvascular architecture in a chronic model of type 1 Diabetes Mellitus

EZQUER, FE; GATICA, M; ARREDONDO, V; GIRAUD BILLOUD, M; CONGET, PA; EZQUER, ME

Las Vegas

Congreso; ISCT 2015 Annual Meeting; 2015

ISCT

The most detrimental complication of Diabetes Mellitus (DM) is Diabetic nephropaty (DN) a clinical syndrome comprised of kidney damage and increased risk of cardiovascular disease. Until now, there is no cure for DN; and treatments only helps to slow its progression. The aim of this study was to evaluate the renoprotective effect of mesenchymal stem cells (MSCs) in a chronic model of type 1 DM. C57BL/6 mice rendered diabetic by administration of a single dose high dose of streptozotocin, received intravenously a single dose of MSCs (0,5x106) at 8 weeks after diabetes induction, since at this time diabetic mice presented functional and structural renal alterations. MSCs renoprotection after was evaluated 2 and 8 weeks post-administration. Compared with untreated animals, MSCs-treated mice showed a supressed increase in kidney weight, kidney to body weight index, albuminuria (ELISA) serum creatinine and BUN (enzymatic). These changes were correlated with increased proliferation rate (PCNA), and decreased apoptosis rate (TUNEL). Furthermore, MSC administration restored glomerular capillary surface area (dextran-FITC by confocal microscopy -CM-), and affacement of podocyte foot processes (podoplanin by CM) associated with nephrin expression. we assessed the level of renal cytokines by RT-qPCR and multiplex array. Compared with normal mice, untreated animals pro-inflammatory molecules were increased and anti-inflammatory molecules were diminished. This pattern was almost normalized in MSCs-treated mice. More importantly the number of infiltrated macrophages (by CM) in kidney was effectively suppressed by MSC treatment. Although donor cells were found in the kidney of treated mice, their scarcity suggests that the improvement in kidney function was not mediated by the differentiation of MSCs into renal cells, so we suppose the participation of paracrine mechanisms to limit the progression of DN in MSCs-treated mice.