MSC-Derived Extracellular Vesicles to Heal Diabetic Wounds: a Systematic Review and Meta-Analysis of Preclinical Animal Studies

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Abstract

Extracellular vesicles from mesenchymal stromal cells (MSC-EVs) have shown promise in wound healing.  Extracellular vesicles are lipid bilayer-delimited particles that are naturally released from a cell and, unlike a cell, cannot replicate.  Extracellular vesicles range in diameter from near the size of the smallest physically possible unilamellar liposome (around 20-30 nanometers) to as large as 10 microns or more, although the vast majority of  Extracellular vesicles are smaller than 200 nm. They carry a cargo of proteins,nucleic acids, lipids, metabolites, and even organelles from the parent cell. Most cells that have been studied to date are thought to release  Extracellular vesicles, including some archaeal, bacterial, fungal, and plant cells that are surrounded by cell walls. Their use in diabetic wounds specifically, however, remains pre-clinical and their efficacy remains uncertain less clear.

 The administration of MSC-EVs improved closure of diabetic wounds compared to controls with a large observed effect. Healing was further enhanced using MSC-EVs enriched in non-coding RNAs or microRNAs compared to controls . Other outcomes, such as blood vessel density and number, scar width, and re-epithelialization were improved with the administration of MSC-EVs, with a large effect.

Conclusion: Extracellular vesicles, particularly following enrichment for specific RNAs, are a promising treatment for diabetic wounds in pre-clinical studies and translation to the clinical domain appears warranted.

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