Therapeutic effects of mesenchymal stem cell conditioned media on streptozotocin-induced diabetes in Wistar rats

Abstract

Cell-based therapy is a new direction of treatment of diseases such as type 1 diabetes mellitus (T1DM); but unfortunately, its severe side effects include immunogenicity and tumor development. Using Mesenchymal stem cells conditioned medium (MSCs-CM) may be an alternative therapy to avoid stem cell risks, preserving effectiveness and demonstrating noticeably increased levels of cytokines, angiogenic factors, and growth factors that encourage and support regenerative processes. In the current work, we examined the effects of MSCs-CM injected in tail vein and pancreas directly compared with the standard antidiabetic drug, glimepiride in streptozotocin-induced type 1 diabetic rats. Fifty adults Male Wistar rats were allocated equally into five groups: normal, diabetic control and three diabetic groups treated respectively with glimepiride, MSCs-CM injected daily into tail vein (MSCs-CMT) and MSCs-CM injected directly in pancreas (MSCs-CMP); all treatments continued for 28 days. The treatments produced a significant improvement in blood glucose level and glycosylated hemoglobin A1c (HbA1c), serum insulin level and lipid panel, and pancreas apoptosis-related markers including B cell lymphoma-2 (Bcl-2) and vimentin. In addition, the treatments resulted in suppression in the oxidation stress and enhancement in the antioxidant, which were manifested by the suppressed lipid peroxidation and the increased antioxidant markers (glutathione, catalase and superoxide dismutase) in the pancreas. In association with the significant decrease in tumour necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) and a significant increase in interleukin-10 (IL-10) levels, the inflammatory mediator nuclear factor-kappa B (NF-κB) expression was significantly decreased by MSCs-CMT and MSCs-CMP. The histological amelioration of the pancreatic islet cells assured our study especially in MSCs-CMP group than MSCs-CMT which supports islet regeneration and elevated circulating insulin. These results imply that MSCs-CM infusion has therapeutic benefits in T1DM rats and may be a viable novel therapeutic approach; MSCs-CMP was shown to be more effective than glimepiride and MSCs-CMT. The mechanisms of antidiabtic actions may be mediated via the antioxidant, anti-apoptotic and anti-inflammatory effects.

Keywords

• Mesenchymal-stem cells conditioned media
• Streptozotocin
• Diabetes mellitus
• Wistar rats