Proregenerative Microenvironment Triggered by Donor Mesenchymal Stem Cells Preserves Renal Function and Structure in
Fernando Ezquer1, Maximiliano Giraud-Billoud2, Daniel Carpio3
1Centro de Medicina Regenerativa, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Avenida Las Condes 12438, Santiago, Chile.
Abstract:
The aim of our work was to evaluate, in an animal model of severe diabetes mellitus, the effect of mesenchymal stem cells (MSCs) administration on diabetic nephropathy (DN) progression. After diabetes induction, one group of mice received the vehicle (DM) and other group received a single dose of MSCs (DM + MSCs). DM + MSCs mice showed a significant improvement in functional parameters of the kidney compared with untreated mice. While DM mice presented marked histopathological changes characteristics of advanced stages of DN (fibrosis, glomerulosclerosis, glomerular basement membrane thickening, capillary occlusion, decreased podocyte density, and effacement of foot processes), DM + MSCs mice showed only slight tubular dilatation. The renoprotection was not associated with an improvement in diabetic condition and 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, DM + MSC mice presented increased renal proliferation index, decreased renal apoptotic index and the restoration of proregenerative factors, and anti-inflammatory cytokines levels. Moreover, macrophage infiltration and oxidative stress damage were also reduced in DM + MSCs mice. Our data demonstrate that MSC administration triggers a proregenerative microenvironment in DN kidney, which allows the preservation of the renal function even if diabetes was uncorrected.
Insights
Mesenchymal stem cells (MSCs) treatment improved kidney function in a severe diabetes mellitus model. MSCs promoted a pro-regenerative kidney environment, preserving renal function without correcting diabetes.
Area of Science:
- Nephrology
- Regenerative Medicine
- Stem Cell Therapy
Background:
- Diabetic nephropathy (DN) is a severe complication of diabetes mellitus.
- DN progression involves significant histopathological changes in the kidney.
- Current treatments for DN are limited in efficacy.
Purpose of the Study:
- To evaluate the effect of mesenchymal stem cells (MSCs) on diabetic nephropathy progression in an animal model.
- To investigate the mechanisms underlying MSC-mediated renoprotection.
Main Methods:
- Induction of diabetes mellitus in mice.
- Administration of a single dose of MSCs or vehicle.
- Assessment of kidney function, histopathology, and molecular markers.
Main Results:
- MSC treatment significantly improved kidney function and reduced histopathological damage compared to controls.
- MSC treatment did not improve the diabetic condition; few donor cells were detected in the kidneys.
- MSC treatment increased renal proliferation, decreased apoptosis, restored pro-regenerative factors, and reduced inflammation and oxidative stress.
Conclusions:
- MSC administration triggers a pro-regenerative kidney microenvironment in DN.
- MSC-mediated renoprotection is likely due to paracrine effects, not cell engraftment.
- MSC therapy offers a potential strategy for preserving renal function in diabetic nephropathy.
