Key Takeaways & Executive Findings
- •• Combined MSC and irbesartan therapy significantly reduces proteinuria, renal dysfunction, and inflammation in diabetic nephropathy rats. • MSCs home to damaged kidneys, enhancing targeted delivery of therapeutic effects. • The combination outperforms monotherapy in protecting glomerular podocytes, suggesting a synergistic mechanism. • Findings support potential clinical translation of MSC-based combination therapy for diabetic nephropathy.
Abstract
Background The leading cause of end-stage renal disease (ESRD) is diabetic nephropathy (DN). Podocyte damage is an early event in the development of DN. Currently, there is no effective treatment strategy that can slow the progression of DN or reverse its onset. The role of mesenchymal stem cells (MSCs) transplantation in diabetes and its complications has been extensively studied, and diabetic nephropathy has been a major focus. Irbesartan exerts reno-protective effects independent of lowering blood pressure, can reduce the incidence of proteinuria in rats, and is widely used clinically. However, it remains undetermined whether the combined utilization of the angiotensin II receptor antagonist irbesartan and MSCs could enhance efficacy in addressing DN. Methods A commonly used method for modeling type 2 diabetic nephropathy (T2DN) was established using a high-fat diet and a single low-dose injection of STZ (35 mg/kg). The animals were divided into the following 5 groups: (1) the control group (CON), (2) the diabetic nephropathy group (DN), (3) the mesenchymal stem cells treatment group (MSCs), (4) the irbesartan treatment group (Irb), and (5) the combined administration group (MSC+Irb). MSCs (2×10^6 cells/rat) were injected every 10 days through the tail vein for a total of three injections; irbesartan (30 mg/kg/d) was administered by gavage. Additionally, the safety and homing of mesenchymal stem cells were verified using positron emission tomography (PET) imaging. Results The combination treatment significantly reduced the UACR, kidney index, IGPTT, HOMA-IR, BUN, serum creatine, and related inflammatory factor levels and significantly improved renal function parameters and the expression of proteins related to glomerular podocyte injury in rats. Moreover, MSCs can homing target to damaged kidneys. Conclusions Compared to the administration of MSCs or irbesartan alone, the combination of MSCs and irbesartan exerted better protective effects on glomerular podocyte injury, providing new ideas for the clinical application of mesenchymal stem cells.
1. Introduction
Diabetes mellitus (DM) is an intractable global health challenge, and the number of people suffering from this disease reached 451 million worldwide as of 2017 and is projected to increase to 552 million by 2030 [1]. Approximately 20–40% of people with diabetes suffer from diabetic nephropathy, particularly those with type 2 diabetes mellitus (T2DM) [2].
Diabetic nephropathy (DN) is a type of kidney disease caused by chronic high blood glucose and is one of the most common and serious complications of diabetes. In the early stages of diabetic nephropathy, the glomeruli are damaged, and microalbumin is present in the urine, which is often one of the first signs. If not controlled in time, the patient’s condition will rapidly deteriorate, and the patient will eventually develop end-stage renal disease (ESRD) and require hemodialysis or even kidney transplantation [3].
The pathogenesis of DN has not been fully elucidated, but the role of chronic inflammation induced by prolonged hyperglycemia in podocyte injury has received increasing attention. Podocytes are major components of the glomerular filtration barrier (GFB) [4], thus, podocyte injury impairs GFB integrity and is strongly associated with diffuse glomerulosclerosis and ESRD [5].
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Jing Meng, Xiao Gao, Xiaojuan Liu, Wen Zheng, Yang Wang, Yinghao Wang, Zhenquan Sun, Xiaoxing Yin, Xueyan Zhou (2026). Effects of xenogeneic transplantation of umbilical cord-derived mesenchymal stem cells combined with irbesartan on renal podocyte damage in diabetic rats. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-024-03844-8
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Frequently Asked Questions
What is the main finding of this study?
The combination of umbilical cord-derived mesenchymal stem cells (MSCs) and irbesartan significantly improves renal function and reduces podocyte damage in diabetic rats, outperforming either treatment alone.
How was diabetic nephropathy induced in the rat model?
Type 2 diabetic nephropathy was induced using a high-fat diet and a single low-dose injection of streptozotocin (STZ) at 35 mg/kg.
What are the key mechanisms behind the protective effects?
The combination therapy reduces inflammatory cytokine levels, improves glomerular podocyte integrity, and MSCs home to damaged kidneys, enhancing targeted therapeutic effects.
What is the clinical significance of this research?
The findings suggest that combining MSCs with irbesartan could be a promising therapeutic strategy for diabetic nephropathy, potentially slowing disease progression and reducing the need for dialysis or transplantation.
What are the limitations of the study?
The study is based on an animal model, and further research is needed to validate the efficacy and safety in human clinical trials.
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