Abstract
BackgroundBy 2030, diabetes mellitus (DM) will be the 7th leading cause of death worldwide. Type 2 DM (T2DM) is the most common type of DM and is characterized by insulin resistance and defective β-cell secretory function. Stem cells from human exfoliated deciduous teeth (SHED) are favorable seed cells for mesenchymal stem cells (MSCs)-based therapy due to their higher proliferation rates and easier access to retrieval. Currently, no study has revealed the therapeutic efficiency of MSCs for T2DM in Goto-Kakizaki (GK) rats. Hence, we aimed to explore the effect of SHED on T2DM in GK rats.Materials and methodsWe investigated the effects of SHED on the progression of T2DM in GK rats. SHED and bone marrow mesenchymal stem cells (BMSCs) were injected via the tail vein. Body weight, fasting blood glucose and non-fasting blood glucose were measured before and after administration. At 8 weeks after injection, intraperitoneal insulin tolerance tests (IPITTs) and insulin release tests (IRTs) were performed. Additionally, hematoxylin–eosin (HE) staining, periodic acid-Schiff (PAS) staining and double-label immunofluorescence staining were used to explore the pathological changes in pancreatic islets and the liver. Immunohistochemistry (IHC) was employed to detect SHED engraftment in the liver. Additionally, real-time PCR and western blotting were used to explore glycogen synthesis, glycolysis and gluconeogenesis in the liver.ResultsAt 8 weeks after SHED injection, T2DM was dramatically attenuated, including hyperglycemia, IPGTT and IRT. Additionally, histological analysis showed that SHED injection improved pancreatic islet and liver damage. Real-time PCR analysis showed that SHED significantly reversed the diabetic-induced increase of G-6-Pase, Pck1 and PK; and significantly reversed the diabetic-induced decrease of GSK3β, GLUT2, and PFKL. In addition, western blotting demonstrated that SHED significantly reversed the diabetic-induced increase of G-6-Pase and reversed the diabetic-induced decrease of GLUT2, GSK3β and PFKM.ConclusionStem cells from human exfoliated deciduous teeth offers a potentially effective therapeutic modality for ameliorating T2DM, including hyperglycemia, insulin resistance, pancreatic islets and liver damage, and decreased glycogen synthesis, inhibited glycolysis and increased gluconeogenesis in the liver.
Highlights
By 2030, diabetes mellitus (DM) will be the 7th leading cause of death worldwide
Histological analysis showed that Stem cells from human exfoliated deciduous teeth (SHED) injection improved pancreatic islet and liver damage
Real-time polymerase chain reaction (PCR) analysis showed that SHED significantly reversed the diabetic-induced increase of G-6-Pase, Pck1 and PK; and significantly reversed the diabetic-induced decrease of GSK3β, GLUT2, and PFKL
Summary
Type 2 DM (T2DM) is the most common type of DM and is characterized by insulin resistance and defective β-cell secretory function. T2DM is the most common type of DM and is characterized by progressively inexorable β-cell dysfunction and insulin resistance in skeletal muscle, adipose tissue, and the liver [2]. MSCs appear to be an ideal tool for treating DM and the related secondary complications as the cells can be isolated from bone marrow, adipose tissue, cord blood and dental pulp and can be rapidly expanded in vitro [6]. MSCs home to injured organs, contribute to tissue regeneration and have been transplanted into human patients with different diseases with beneficial effects and without major toxicity [7,8,9]. The biological effects of these trophic factors can be direct (triggering intracellular signaling) or indirect (inducing neighboring cells to secrete other bioactive factors) [21, 22]
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