Abstract
Mesenchymal stromal cells (MSCs) are applied in regenerative medicine of several tissues and organs nowadays by virtue of their self-renewal capabilities, multiple differentiation capacity, potent immunomodulatory properties, and their ability to be favourably cultured and manipulated. With the continuous development of “cell-free therapy” research, MSC-derived small extracellular vesicles (MSC-sEVs) have increasingly become a research hotspot in the treatment of various diseases. Small extracellular vesicles (SEVs) are membrane vesicles with diameters of 30 to 150 nm that mediate signal transduction between adjacent or distal cells or organs by delivering non-coding RNA, protein, and DNA. The contents and effects of sEVs vary depending on the properties of the originating cell. In recent years, MSC-sEVs have been found to play an important role in the occurrence and development of diabetes mellitus as a new way of communication between cells. Diabetes mellitus is a common metabolic disease in clinic. Its complications of the heart, brain, kidney, eyes, and peripheral nerves are a serious threat to human health and has been a hot issue for clinicians. MSC-sEVs could be applied to repair or prevent damage from the complications of diabetes mellitus through anti-inflammatory effects, reduction of endoplasmic reticulum-related protein stress, polarization of M2 macrophages, and increasing autophagy. Therefore, we highly recommend that MSC-sEVs-based therapies to treat diabetes mellitus and its chronic complication be further explored. The analysis of the role and molecular mechanisms of MSC-sEVs in diabetes and its related complications will provide new idea and insights for the prevention and treatment of diabetes.
Highlights
Diabetes is a group of metabolic diseases characterized by chronic hyperglycemia caused by multiple causes
The results showed that, after treatment with small extracellular vesicles (sEVs), the expression of tumor necrosis factor-a (TNF-a) in nerve tissues was reduced, and the levels of TGF-b, IL-10, and Arg1 increased, indicating that exosome treatment reversed the increase in M1 type macrophages and the decrease in M2 type macrophages caused by diabetes, which is achieved by the polarization of macrophages M2 to reduce inflammation and improve neurovascular function
With a more complete understanding of the mechanisms driving sEVs formation, sEVs could be engineered as vectors for the targeted delivery of molecular therapies injection of these sEVs would, in theory, allow for the discriminate delivery of medicine directly into specific target cells
Summary
Diabetes is a group of metabolic diseases characterized by chronic hyperglycemia caused by multiple causes It is caused by defects in insulin secretion and/or function. Numerous studies have shown that the therapeutic effects of MSCs are mediated in a paracrine manner, mainly through extracellular vesicles such as small extracellular vesicles (sEVs) [15]. Existing studies have shown that MSC-sEVs have a therapeutic effect on diabetes [16, 17]. The regenerative and immunomodulatory properties of MSC-sEVs have the potential to treat diabetes and related complications, such as diabetic nephropathy (DN) [18] and central nervous system damage [19]. The role of MSC-sEVs in the treatment of diabetes diseases is an area of active preclinical study. The diabetes-based existence of a chronic inflammatory state, impaired immune response, impaired coagulation and other related complications could be among the underlying pathophysiological mechanisms contributing to the increased morbidity and mortality of people with diabetes
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