MSC transplantation: a promising therapeutic strategy to manage the onset and progression of diabetic nephropathy

Abstract

Currently, one of the main threats to public health is diabetes mellitus. Its most detrimental complication is diabetic nephropathy (DN), a clinical syndrome associated with kidney damage and an increased risk of cardiovascular disease. Irrespective of the type of diabetes, DN follows a well-known temporal course. The earliest detectable signs are microalbuminuria and histopathological changes including extracellular matrix deposition, glomerular basement membrane thickening, glomerular and mesangial expansion. Later on macroalbuminuria appears, followed by a progressive decline in glomerular fi ltration rate and the loss of glomerular podocytes, tubulointerstitial fi brosis, glomerulosclerosis and arteriolar hyalinosis. Tight glycemic and hypertension controls remain the key factors for preventing or arresting the progression of DN. Nevertheless, despite considerable educational eff ort to control the disease, a signifi cant number of patients not only develop DN, but also progress to chronic kidney disease. Therefore, the availability of a strategy aimed to prevent, delay or revert DN would be highly desirable. In this article, we review the pathophysiological features of DN and the therapeutic mechanisms of multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs). The perfect match between them, together with encouraging pre-clinical data available, allow us to support the notion that MSC transplantation is a promising therapeutic strategy to manage DN onset and progression, not only because of the safety of this procedure, but mainly because of the renoprotective potential of MSCs.

Recent Progress in Stem Cell Therapy for Diabetic Nephropathy

“…In preclinical studies, administration of MSCs has also shown potential to treat DN in several animal models. Injection of MSCs into streptozotocin (STZ)-induced type 1 diabetic mice improved renal and pancreatic function [33,34] . In NOD/SCID mice, human MSCs decreased mesangial thickening and reduced macrophage infiltration [35] .…”

Mechanistic Insight and Management of Diabetic Nephropathy: Recent Progress and Future Perspective

“…Furthermore, the present study shows reductions in subsets of stem cells in peripheral blood and renal cell preparations of db/db mice which is a model of DN, which indicates that the decrease of stem cells might be a hallmark of DN [66, 67]. MSC transplantation is a promising therapeutic strategy to delay DN progression in animal models; however, the clinical trials should be performed to investigate the safety and efficacy of MSC transplantation in patients with DN [68]. Overall, stem cells could be used as an early diagnosis marker of DN and have a tendency to play much more important roles in the future.…”

Stem Cell-Based Cell Therapy for Glomerulonephritis

“…It is reported that the low susceptibility of MSCs to the deleterious effect of ROS and reactive nitrogen species correlates with the ability of these cells to effectively scavenge peroxide and peroxynitrite, due to the constitutive expression of SOD1, SOD2, CAT, and GPX1 enzymes and high levels of glutathione. MSCs possess the main enzymatic mechanisms to detoxify reactive species and to prevent oxidative damage of the proteome and genome [91]. …”