Melatonin Promotes the Therapeutic Effect of Mesenchymal Stem Cells on Type 2 Diabetes Mellitus by Regulating TGF-β Pathway

Abstract

Abundant evidence proves the therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) in the treatment of diabetes mellitus. However, the problems have not been solved that viability of ADMSCs were inconsistent and the cells quickly undergo senescence after in vitro cell culture. In addition, the therapeutic effect of ADMSCs is still not satisfactory. In this study, melatonin (MLT) was added to canine ADMSC culture medium, and the treated cells were used to treat type 2 diabetes mellitus (T2DM). Our research reveals that adding MLT to ADMSC culture medium can promote the viability of ADMSCs. This effect depends on the binding of MLT and MLT receptors, which activates the transforming growth factor β (TGF-β) pathway and then changes the cell cycle of ADMSCs and improves the viability of ADMSCs. Since ADMSCs were found to be used to treat T2DM by anti-inflammatory and anti-endoplasmic reticulum (ER) stress capabilities, our data demonstrate that MLT augment several effects of ADMSCs in remission hyperglycemia, insulin resistance, and liver glycogen metabolism in T2DM patients. This suggest that ADMSCs and MLT-ADMSCs is safe and vabulable for pet clinic.

Melatonin treatment improves human umbilical cord mesenchymal stem cell therapy in a mouse model of type II diabetes mellitus via the PI3K/AKT signaling pathway

“…In this experiment, we developed a novel strategy based on a specific small molecule (melatonin) to preserve the stemness of hUC-MSCs. Treatment with low-dose melatonin relieves the senescence of MSCs and increases the proliferation and differentiation of MSCs [ 12 , 22 ]. On the other hand, the combination of melatonin with MSCs in clinical application has not been reported.…”

“…The pathophysiology of T2DM, also known as chronic disease and insulin-independent diabetes mellitus, is characterized by a state of persistent insulin resistance, pancreatic beta-cell dysfunction, abnormal incretin effect, hyperglycemia and excessive cell glucagon production are interrelated defects [ 22 – 25 ]. The prominent characteristic of T2DM is insulin resistance, which impairs the action of insulin.…”

Injectable Peptide Hydrogel Encapsulation of Mesenchymal Stem Cells Improved Viability, Stemness, Anti-Inflammatory Effects, and Early Stage Wound Healing

“…MSCs can generate and secrete a large variety of bioactive factors that can modulate immune response [ 2 , 3 , 4 ], promote angiogenesis [ 5 ], stimulate cell survival and proliferation, and affect differentiation of specific cells for tissue repair [ 6 ]. Studies have demonstrated great potential of MSCs and their secretome in alleviation or treatment of diseases, such as osteoarthritis [ 7 , 8 , 9 , 10 , 11 ], type 2 diabetes mellitus [ 12 , 13 ], obesity-induced metabolic dysregulation [ 14 ], cardiovascular diseases [ 5 ], and graft-versus-host disease (GVHD) [ 4 ]. Allogeneic MSC transplants were proven safe by multiple clinical studies [ 15 , 16 , 17 ], which expands therapeutic potentials of MSCs.…”

Melatonin alleviates PM2.5‐induced glucose metabolism disorder and lipidome alteration by regulating endoplasmic reticulum stress

“…Melatonin is involved in regulating a diverse range of physiological functions (e.g., sleep, mood, and reproduction). Besides its well‐known antioxidative stress effects, melatonin also restores glucose metabolic dysregulation in T2DM mice and repairs hepatic lipid accumulation to normal levels caused by ER stress 18 . A recent study showed that PM 2.5 not only promotes melatonin synthesis in the lung but also suppresses daily plasma melatonin rhythm 19 .…”

“…Besides its well-known antioxidative stress effects, melatonin also restores glucose metabolic dysregulation in T2DM mice and repairs hepatic lipid accumulation to normal levels caused by ER stress. 18 A recent study showed that PM 2.5 not only promotes melatonin synthesis in the lung but also suppresses daily plasma melatonin rhythm. 19 This makes it important to explore the relationship between exogenous melatonin supplementation and air pollution.…”