October 6, 2022

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Stem cells: Mechanisms for intervention and treatment of metabolic syndrome

Clinically discovered that the three major mechanisms of stem cells have become the main mechanisms for intervention and treatment of metabolic syndrome

 

Stem cells: Mechanisms for intervention and treatment of metabolic syndrome.  The theoretical basis and experimental research of mesenchymal stem cells in the treatment of various diseases through regeneration, direct repair, immune regulation and other mechanisms provide new ideas for the clinical application of Mscs in the treatment of metabolic syndrome.

Metabolic syndrome (Ms) is a general term for a group of metabolic diseases that are mainly characterized by insulin resistance, which can cause obesity, hypertension, hyperglycemia, and dyslipidemia, and lead to a significantly increased risk of cardiovascular disease and diabetes.

 

At present, the treatment of MS mainly focuses on improving lifestyle and drug therapy. These treatments require patients to have strong compliance, have adverse drug reactions, and it is difficult to fundamentally improve and cure MS.

Mesenchymal stem cells (MSCs) are cells with self-replication ability and multiple differentiation potentials. At present, the application of MSCs in disorders of glucose and lipid metabolism, insulin resistance, hypertension and cardiovascular diseases has been reported.

Mesenchymal stem cells derived from embryos, umbilical cord, bone marrow and fat are currently used in the treatment of metabolic syndrome.

 

 

Three Mechanisms of Mesenchymal Thousand Cells in Treating Metabolic Syndrome

The secretory effect of mesenchymal stem cells inhibits chronic inflammation and reduces obesity

Studies have confirmed that obesity is a systemic chronic low-grade inflammation. This inflammatory state provides the best “environment” for the occurrence and development of MS.

Hypertrophic adipocytes secrete MCP-1 and other chemokines to recruit monocytes and macrophages to accumulate in adipose tissue to cause inflammation, and at the same time secrete a large number of inflammatory factors; secondly, local hypoxia and endoplasmic reticulum stress Etc. can promote the expression and secretion of inflammatory factors (IL-6, TNF-α, etc.) by activating the inflammatory signal pathway.

Therefore, controlling obesity-related inflammation is a key link in controlling the occurrence and development of Ms. As an important cell for regeneration and repair, MSCs have been confirmed to play an anti-inflammatory and immune regulatory role through their secretion mechanism.

 

The secretion of mesenchymal stem cells effectively improves the body’s insulin resistance

Insulin resistance (IR) is another important trigger of Ms, and inflammation is an important cause of IR.

In Diabetes, it was first proposed and confirmed that BMMSCs can relieve hyperglycemia by improving pancreatic β-cell function and peripheral target tissue insulin resistance in the early stage of infusion, while in the late stage of infusion, it can achieve long-term blood glucose control by improving peripheral tissue insulin resistance the goal of.

In vitro experiments confirmed that BMMscs can reduce blood glucose by activating skeletal muscle, fat, and liver insulin receptor substrates-1-AKT-GLUT signaling pathway to improve insulin resistance in peripheral tissues.

 

Mesenchymal stem cells promote blood vessel regeneration and repair myocardium, effectively improve blood circulation

When tissues and cells of the body are damaged, the damaged blood vessels, cells and the released inflammatory factors (TNF-α, IL-1β, etc.) activate immune cells such as macrophages, neutrophils, T cells and β cells. In the microenvironment of damaged tissues, Mscs are recruited to the damaged site to differentiate into vascular endothelial cells, cardiomyocytes and smooth muscle cells, and directly participate in angiogenesis and repair of damaged myocardium.

In addition, Mscs can secrete pro-angiogenic molecules, such as vascular endothelial growth factor, hepatocyte growth factor, basic fibroblast growth factor, transforming growth factor-β and insulin-like growth factor-1 to promote the self-repair of blood vessels .

In general, various experimental data and clinical evidence have shown that MSCs transplantation can promote vascular regeneration and repair damaged cardiomyocytes, thereby improving heart function and blood circulation.

 

Original idea

Zhao et al. in 2011 [1], Gopurappilly and Bhonde [2] in 2012 successively proposed the hypothesis that “Mscs treats type 2 diabetes by regulating IR”.

Stem cells: Mechanisms for intervention and treatment of metabolic syndrome

 

Basic research

At the same time, an experimental study on the treatment of type 2 diabetic rats induced by high-sugar and high-fat diet combined with injection of streptomycin by infusion of bone marrow-derived mesenchymal stem cells (BMMscs).

It was further confirmed that intravenous infusion of rat BMMscs significantly improved the IR index of rats, enhanced the P13K-AKT signal in the insulin target tissue, promoted the expression of glucose transporter 4 and membrane translocation, and then improved the rat’s With high blood sugar, different degrees of regeneration of pancreatic islets have also been found.

 

Clinical case

In a 2018 clinical trial of MSCs for the treatment of type 2 diabetes, the researchers injected Mscs with 1×10^6kg via peripheral vein directly and via splenic vein into the pancreas on the 5th and 10th day, respectively. Infusions were given to 22 recruited diabetic patients to observe the changes of related indicators before and after cell therapy.

This study confirmed that the patient’s insulin resistance was significantly improved after MSCs infusion, and it was found that the levels of IL-1B and IL-6 in the patient’s serum decreased significantly after 6 months of cell infusion. It is suggested that Mscs may regulate the secretion of inflammation-related factors and improve the IR treatment of MS.

 

Conclusion:

The theoretical basis and experimental research of mesenchymal stem cells in the treatment of various diseases through regeneration, direct repair, immune regulation and other mechanisms provide new ideas for the clinical application of Mscs in the treatment of metabolic syndrome.

The role and molecular mechanism of MScs transplantation in insulin resistance, glucose and lipid metabolism disorders, cardiovascular disease and nephropathy provide more hope and possibilities for further exploration of MSCs transplantation for the treatment of metabolic syndrome, as well as future animal experiments and clinical studies Provide certain background support.

 

(sourceinternet, reference only)


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