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"... Now, a new study led by researchers ... has examined the role of exosomes in diabetics, whose wounds tend to heal more slowly and progress more quickly, increasing the risk of infections and other serious complications. ..."
"... “In patients with diabetes, wound healing is impaired because of excess inflammation,” ... When exosomes, small particles that carry information between cells, do not function properly in patients with diabetes, inflammation can increase and impair wound healing.
Researchers collected bandages containing wound fluid from 22 diabetic and 15 non-diabetic patients in order to isolate and examine exosomes.
They found that if signals contained within the exosomes were correct, then inflammation in the wound would ultimately be resolved. However, they found that diabetic exosomes, or “diaexosomes,” compromised wound healing and led to the production of pro-inflammatory compounds. ..."
From the abstract:
"Exosomes, a class of extracellular vesicles of endocytic origin, play a critical role in paracrine signaling for successful cell-cell crosstalk in vivo. However, limitations in our current understanding of these circulating nanoparticles hinder efficient isolation, characterization, and downstream functional analysis of cell-specific exosomes. In this work, we sought to develop a method to isolate and characterize keratinocyte-originated exosomes (hExoκ) from human chronic wound fluid. Furthermore, we studied the significance of hExoκ in diabetic wounds. LC-MS-MS detection of KRT14 in hExoκ and subsequent validation by Vesiclepedia and Exocarta databases identified surface KRT14 as a reliable marker of hExoκ. dSTORM nanoimaging identified KRT14+ extracellular vesicles (EVκ) in human chronic wound fluid, 23% of which were of exosomal origin. An immunomagnetic two-step separation method using KRT14 and tetraspanin antibodies successfully isolated hExoκ from the heterogeneous pool of EV in chronic wound fluid of 15 non-diabetic and 22 diabetic patients. Isolated hExoκ (Ø 75–150 nm) were characterized per EV-track guidelines. dSTORM images, analyzed using online CODI platform followed by independent validation using Nanometrix, revealed hExoκ Ø as 80–145 nm. The abundance of hExoκ was low in diabetic wound fluids and negatively correlated with patient HbA1c levels. The hExoκ isolated from diabetic wound fluid showed a low abundance of small bp RNA (<200 bp). Raman spectroscopy underscored differences in surface lipids between non-diabetic and diabetic hExoκ. Uptake of hExoκ by monocyte-derived macrophages (MDM) was low for diabetics versus non-diabetics. Unlike hExoκ from non-diabetics, the addition of diabetic hExoκ to MDM polarized with LPS and INFγ resulted in sustained expression of iNOS and pro-inflammatory chemokines known to recruit macrophages (mϕ).This work provides maiden insight into the structure, composition, and function of hExoκ from chronic wound fluid thus providing a foundation for the study of exosomal malfunction under conditions of diabetic complications such as wound chronicity."
Skin cells at the edge of a diabetic wound. Red and green colors depict two proteins involved in the release of exosomes from these cells
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