Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapy for Diabetes Mellitus and Diabetic Complications

Abstract

As a novel cell-free strategy, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) inherit the therapeutic potential of donor cells, and are widely used for the treatment of many diseases. Increasing studies have shown that MSC-EVs transfer various bioactive molecules to create a beneficial microenvironment, thus exerting protective roles in diabetic mellitus (DM) and diabetic complications. To overcome the limitations of natural MSC-EVs such as heterogeneity and insufficient function, several modification methods have been established for constructing engineered MSC-EVs with elevated repairing efficiency. In this review, the PubMed library was searched from inception to August 2022, using a combination of Medical Subject Headings (MeSH) and keywords related to MSC-EVs, DM, and diabetic complications. We provide an overview of the major characteristics of MSC-EVs and summarize the recent advances of MSC-EV-based therapy for hyperglycemia-induced tissue damage with an emphasis on MSC-EV-mediated delivery of functional components. Moreover, the potential applications of engineered MSC-EVs in DM-related diseases therapy are discussed by presenting examples, and the opportunities and challenges for the clinical translation of MSC-EVs, especially engineered MSC-EVs, are evaluated.

Research progress in the treatment of cardiovascular diseases with extracellular vesicles

“…For example, in the model of type I diabetes and retinitis, MSC EVs are as effective as MSCs in inhibiting autoimmunity. In addition, the effect of MSC-EVs on acute kidney injury is similar to that of MSCs [9]. These observations indicate that MSC EVs can serve as substitutes for MSC based cell therapy.…”

Advancing diabetes treatment: the role of mesenchymal stem cells in islet transplantation

“…Clinical studies have confirmed the ability of MSCs to evolve into insulin-producing cells and secrete healing factors, positioning them as key players in T1D treatment ( 26 ). Furthermore, engineered MSC-derived EVs are being developed to enhance regenerative efficacy, overcoming natural limitations ( 27 ). Proteomic analyses of MSC exosomes from various sources have revealed that shared mechanisms, notably extracellular matrix interactions, are crucial for their regenerative impact ( 28 ).…”

Regulation of the Nrf2/HO-1 axis by mesenchymal stem cells-derived extracellular vesicles: implications for disease treatment

“…Compared to existing treatments like laser photocoagulation, VEGF inhibitors, and corticosteroids, which often target specific symptoms or disease aspects, MSC-EVs could potentially offer a more comprehensive approach by addressing inflammation, oxidative stress, and cell death. However, for MSC-EV therapy to be clinically feasible, improvements in the formulation and administration techniques are necessary to enhance delivery, efficacy, and the practicality of their use in clinical settings ( Sun et al, 2022b ).…”