Exosome RNA Exosome RNA Research & Industry News
Cutaneous Leishmaniasis is a parasitic disease that causes skin lesions and tissue damage. Researchers led by the first author from the Instituto Gonçalo Moniz investigated whether extracellular vesicles, or EVs, released by human umbilical cord mesenchymal stem cells (hUCMSC-EVs), could help fight the infection and promote tissue repair.
Functional enrichment and protein–protein interaction analysis of
hUCMSC-EV proteome and genes overexpressed in infected skin
A Gene Ontology (GO) analysis showing key biological processes enriched in the hUCMSC-EV proteome, including parental terms. B Sankey diagram highlighting key biological processes, including protein catabolic processes and response to stress, and their connection to wound healing, immune regulation, and defense responses. The color gradient represents the degree of enrichment, with darker shades indicating higher enrichment. C High-confidence protein–protein interaction (PPI) network performed by STRING integrating hUCMSC-EV proteins and proteins encoded by DEGs in CL lesions. Nodes represent proteins, with EV-derived proteins shown in orange and proteins encoded by upregulated CL DEGs shown in blue. Edges indicate high-confidence interactions (score > 0.9). Key proteins in CL lesions involved in extracellular matrix (ECM) remodeling, including COL3A1, COL5A1, COL5A2, and MMPs, are highlighted, along with their interactions with proteins from hUCMSC-EVs (FN1, TIMP1, ANXA1, ANXA2, and SERPINE1). D PPI subnetwork showing interactions between lesion-derived proteins (TNF, TGFB, IL10) and EV-derived proteins (TIMP1, DCN, UBC), emphasizing their roles in inflammatory signaling and ECM organization
In lab experiments, these EVs were applied to macrophages, a type of immune cell, that were infected with the parasite Leishmania braziliensis. The EVs helped the macrophages adopt a mixed M1/M2 profile, boosting both inflammatory and regulatory signals, increasing TNF-α and IL-10 secretion, and reducing the number of parasites inside the cells. Protein analysis of the EVs revealed molecules involved in wound healing, which was confirmed in tests where cells were monitored for migration and closure of artificial scratches.
In animal experiments, intravenous injection of hUCMSC-EVs into infected mice reduced lesion thickness and decreased collagen buildup at the site of infection. These findings indicate that the EVs not only enhance parasite clearance but also support tissue repair.
Overall, hUCMSC-EVs show potential as an adjunctive therapy for Cutaneous Leishmaniasis by modulating the immune response and promoting healing, suggesting broader possibilities for stem cell-derived EVs in treating infectious diseases.
