Potential Therapeutic Effect of TLR4-Primed Mesenchymal Stem Cells in Lessening Kidney Damages in Rat Model of Diabetic Nephropathy

Mohammad  Tollabi; Navid  Ghasemzadeh; Ali  Dehghani Firoozabadi

doi:10.18502/ijml.v9i3.10903

Mohammad Tollabi Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
Navid Ghasemzadeh Department of clinical Biochemistry and applied cell sciences, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
Ali Dehghani Firoozabadi Yazd Cardiovascular Research Center, Non-communicable Diseases Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

DOI: https://doi.org/10.18502/ijml.v9i3.10903

Keywords: Diabetic nephropathy, Inflammation, Mesenchymal stem cells, TLR4 priming

Abstract

Background and Aims: Substantial damage to the kidney tissue and diabetic nephropathy (DN) can be caused by chronic hyperglycemic conditions and exposure to a high level of blood glucose. In the current study, we explored the capability of adipose-derived mesenchymal stem cells (ADSCs) and Toll-like receptor-4-primed mesenchymal stem cells (TLR4-primed MSCs) on kidney regeneration, resolution of inflammation, and alleviation of diabetic nephropathy in DN in the rats.

Materials and Methods: STZ-induced diabetic rat models were divided into 5 subgroups, including 1) DN group, 2) DN group received insulin, 3) DN group received human foreskin fibroblast (DN-HFF), 4) DN group received single pulse of 1×10⁶ cells of MSCs and 5) DN group received single pulse of TLR4-primed MScs. Thereafter, biochemical and histological analysis was performed on DN-model groups. Biochemical analysis exhibited a blood urea nitrogen level recovery in both MSCs and TLR4-primed MSCs-treated groups. Administration of MSCs also up-regulated mRNA expression of Bcl-xL, while the expression of Bax was significantly down-regulated.

Results: Histological and molecular results showed that TLR4-primed MSCs have an anti-inflammatory and anti-apoptotic effect on inflamed kidneys and effectively reduced DN indicators in the TLR4-primed MSCs group compared to the unprimed MSCs group.

Conclusion: Priming with LPS improves the therapeutic effects of MSCs in the rat model of DN, consequently lessening the symptoms of DN rats. This study proposes that primed MSCs can be served as a potential therapeutic approach in diabetes mellitus and DN management.