Efficiency of Bone Marrow-Derived Mesenchymal Stem Cells and Hesperetin in the Treatment of Streptozotocin-Induced Type 1 Diabetes in Wistar Rats

Abstract

Type 1 diabetes mellitus (T1DM) was established to be ameliorated by islet transplantation, but the shortage of the transplanted human islet tissue and the use of immunosuppressive drugs to inhibit the rejection of allogeneic grafts make this type of therapy is limited. Nowadays, therapy with stem cells is one of the most promising future treatments. This kind of therapy could have a profound impact on both replacement, as well as regenerative therapies, to improve or even cure various disorders, including diabetes mellitus. Flavonoids have also been shown to possess anti-diabetic effects. Thus, this study aims to evaluate the effectiveness of the bone marrow-derived mesenchymal stem cells (BM-MSCs) and hesperetin in the treatment of a T1DM rat model. T1DM was induced in male Wistar rats that had been starved for 16 h via intraperitoneal injection of STZ at a dose of 40 mg/kg body weight (b.wt.). After 10 days of STZ injection, the diabetic rats were allocated into four groups. The first diabetic animal group was considered a diabetic control, while the other three diabetic animal groups were treated for six weeks, respectively, with hesperetin (given orally at a dose of 20 mg/kg b.wt.), BM-MSCs (injected intravenously at a dose of 1 × 106 cells/rat/week), and their combination (hesperetin and BM-MSCs). The use of hesperetin and BM-MSCs in the treatment of STZ-induced diabetic animals significantly improved the glycemic state, serum fructosamine, insulin and C-peptide levels, liver glycogen content, glycogen phosphorylase, glucose-6-phosphatase activities, hepatic oxidative stress, and mRNA expressions of NF-κB, IL-1β, IL-10, P53, and Bcl-2 in pancreatic tissue. The study suggested the therapy with both hesperetin and BM-MSCs produced marked antihyperglycemic effects, which may be mediated via their potencies to ameliorate pancreatic islet architecture and insulin secretory response, as well as to decrease hepatic glucose output in diabetic animals. The improvement effects of hesperetin and BM-MSCs on the pancreatic islets of diabetic rats may be mediated via their antioxidant, anti-inflammatory, and antiapoptotic actions.

Mesenchymal Stem Cells and Begacestat Mitigate Amyloid-β 25–35-Induced Cognitive Decline in Rat Dams and Hippocampal Deteriorations in Offspring

“…Female rats underwent surgery as described previously [29]. Free Aβ 25-35 was dissolved to a concentration of 1 mg/mL in 0.9% saline and was aggregated by in vitro incubation at 37 • C for 4 days [29], to obtain a solution of Aβ 25-35 oligomers (oAβ [25][26][27][28][29][30][31][32][33][34][35]. For profound anesthesia, 7 mg/kg xylazine and 70 mg/kg ketamine were injected intraperitoneally into rats.…”

“…Mesenchymal stem cells (MSCs) were extracted from rat bone marrow as described in previous work [30][31][32]. The bone marrow was flushed out of the femur using 4.5% DMEM (Life Science Group Ltd., Sandy, UK), and the solution was centrifuged at 3000 rpm for five minutes.…”

A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome

“…The combined treatment of streptozotocin-induced diabetic rats with bone-marrow-derived MSCs and hesperetin (a citrus flavonoid) improved glucose, insulin, and C-peptide levels. [554] Most of the human studies involved the transplantation of MSCs alone or in combination with mononuclear cells (MNCs) to T1D or T2D patients, which showed promising beneficial effects in terms of improved glucose homeostasis and reduced insulin requirements (Table 4). Autologous MSC transplantation in recent onset T1D patients has been shown to improve glycated HbA1c and C-peptide levels, preserve β-cell function, and shift serum cytokine patterns from pro-inflammatory cytokines to anti-inflammatory cytokines [482,488].…”