Proregenerative Microenvironment Triggered by Donor Mesenchymal Stem Cells Preserves Renal Function and Structure in Mice with Severe Diabetes Mellitus

EZQUER, FE; GIRAUD BILLOUD, M; CARPIO, DJ; CABEZAS, FA; CONGET, PA; EZQUER, ME

BIOMED RESEARCH INTERNATIONAL

Hindawi Pub. Co.

Lugar: New York, NY; Año: 2015 vol. 2015 p. 1 - 23

2314-6133

Diabetic nephropathy (DN) is one of the main causes of end-stage renal disease. Mesenchymal Stem Cells (MSCs) promote regeneration of injured organs, including kidneys. The aim of our work was to evaluate in animal model of severe diabetes mellitus, the effect of MSCs administration on DN progression. Eight weeks after diabetes induction, one group of mice received the vehicle (DM) and other group received a single dose of 0.5x106 MSCs (DM+MSCs). DM+MSCs mice showed a significant improvement in functional parameters of the kidney (reduction in urinary albumin excretion, blood urea nitrogen and plasma creatinine) compared with untreated mice. While, untreated mice presented marked histopathological changes characteristics of advanced stages of DN (glomerular hypertrophy, fibrosis, glomerulosclerosis, glomerular basement membrane thickening, capillary occlusion, decreased podocyte density and effacement of foot processes). DM+MSCs mice showed only slight tubular dilatation and reduced glomerulosclerosis, extracellular matrix protein accumulation and TGF-β1 expression, with preservation of the filtration barrier integrity. The observed renoprotection was not associated with an improvement in diabetic condition since DM+MSCs mice remained hyperglycaemic, hypoinsulinemic and dyslipidemic up to the end of the study. Very low number of donor cells was found in the kidney of DM+MSCs mice, suggesting that renoprotection could be mediated by paracrine effects. Indeed, MSC treated mice presented increased renal proliferation index and a decreased renal apoptotic index, accompanied by the restoration of the circulating levels of the pro-regenerative factors EGF and bFGF, and the anti-inflammatory cytokines IL-4 and IL-10. Moreover, leucocyte infiltration and oxidative stress damage were also reduced by MSC treatment compared with untreated mice. Taken together, our data demonstrate that MSC administration triggers a pro-regenerative microenvironment in DN kidney, which allows the preservation of the renal function even diabetes was uncorrected.