Bone Marrow-Derived Mesenchymal Stem Cells Restored High-Fat-Fed Induced Hyperinsulinemia in Rats at Early Stage of Type 2 Diabetes Mellitus

Abstract

Numerous studies have proposed the transplantation of mesenchymal stem cells (MSCs) in the treatment of typical type 2 diabetes mellitus (T2DM). We aimed to find a new strategy with MSC therapy at an early stage of T2DM to efficiently prevent the progressive deterioration of organic dysfunction. Using the high-fat-fed hyperinsulinemia rat model, we found that before the onset of typical T2DM, bone marrow-derived MSCs (BM-MSCs) significantly attenuated rising insulin with decline in glucose as well as restored lipometabolic disorder and liver dysfunction. BM-MSCs also favored the histological structure recovery and proliferative capacity of pancreatic islet cells. More importantly, BM-MSC administration successfully reversed the abnormal expression of insulin resistance-related proteins including GLUT4, phosphorylated insulin receptor substrate 1, and protein kinase Akt and proinflammatory cytokines IL-6 and TNFα in liver. These findings suggested that MSCs transplantation during hyperinsulinemia could prevent most potential risks of T2DM for patients.

Combinatory Effect and Modes of Action of Chrysin and Bone Marrow-Derived Mesenchymal Stem Cells on Streptozotocin/Nicotinamide-Induced Diabetic Rats

“…The blood C-peptide level was utilized as a good predictor of any change in insulin levels since it was co-secreted with insulin from the pancreatic cells as a consequence of the conversion of proinsulin to insulin ( Figure 8 ) [ 56 ]. In terms of other models of T2DM, our results support those of Li et al [ 19 ], Hussien et al [ 20 ], Si et al [ 22 ], and Hao et al [ 57 ], who reported that BM-MSCs infusions enhanced the status of hyperglycemia, serum C-peptide, and insulin in T2D rats induced by a fat-fed diet and STZ. The ameliorative effect of chrysin and BM-MSCs was also confirmed by the improvement in the histological architecture of the Trichrome-PASS stain and the increase in insulin immunoreactivity.…”

“…One of the most appropriate categories of multipotent adult stem cells, mesenchymal stem cells (MSCs), are readily available from bone marrow (BM), adipose tissues, the umbilical cord, umbilical cord blood, and dental pulp [ 17 , 18 ]. MSCs are undifferentiated cells that possess the properties of self-renewal, the expansion in the presence of culture medium, the activation of endogenous progenitor cells, the modulation of the local environment, the secretion of various factors, and low immunogenicity, but they come with a number of ethical concerns [ 19 , 20 ].…”

“…Recent studies have indicated that BM-derived MSCs (BM-MSCs) could potentially exert anti-diabetic effects in a HFD/STZ rat model of T2DM that resulted in the recovery of pancreatic islets, increased insulin secretion, the correction of hyperglycemia, and ameliorated insulin sensitivity [ 19 , 20 , 21 , 22 ]. In another animal model, the effect of BM-MSCs therapy in NA/STZ-induced T2DM rats was reported by Hamza et al [ 23 ], who stated their potential effects in ameliorating elevated blood glucose levels.…”

Human umbilical cord-derived mesenchymal stem cells prevent the progression of early diabetic nephropathy through inhibiting inflammation and fibrosis

“…The main sources are the bone marrow MSCs (BM-MSCs), adipose-derived MSCs (AD-MSCs), and umbilical cord MSCs (UC-MSCs). A large number of studies have investigated the role of MSCs in many diseases, including diabetic retinopathy [12], myocardial infarction [13], diabetes [14], and DN [15][16][17][18][19] in mice and rats. However, the underlying mechanisms of these beneficial effects are not completely elucidated.…”

Extracellular vesicle microRNA and protein cargo profiling in three clinical-grade stem cell products reveals key functional pathways

“…For over 20 years, BM-MSCs have been studied, with multiple reports supporting utility in several diseases. 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 The BM-MSC lines used in this study were sourced from qualified normal donors, thus avoiding potential adverse effects of medical comorbidities on therapeutic efficacy. Compared with BM-MSCs, UC-MSCs display a more consistent phenotype, higher yields, more rapid growth, and potentially higher therapeutic efficacy (potency).…”