Umbilical cord mesenchymal‐stem‐cell‐derived nanovesicles as a novel strategy to promote wound healing in diabetes

Abstract

Objective: Recent studies found that exosomes (Exo) derived from mesenchymal stem cells (MSC) (MSC-Exo) accelerated diabetic wound healing. However, the low yield during exosome extraction is still a major barrier to their clinical utility. Methods: We constructed a method to produce umbilical cord MSC-derived nanovesicles (UCMSC-NV) by serial extrusion through filters and investigated the effects of UCMSC-NV on wound healing in vivo and in vitro, as well as the potential mechanisms. Results: We found that the characteristics of UCMSC-NV were similar to those of exsome (UCMSC-Exo) but with much higher production yields. Further analysis showed that UCMSC-NV promoted the migration of fibroblasts and angiogenesis in vitro, and both UCMSC-NV and UCMSC-Exo showed similar therapeutic capacities for wound healing in vivo. Sequencing analysis revealed that UCMSC-NV and UCMSC-Exo had similar miRNA compositions, and the target genes of the differentially expressed miRNAs in UCMSC-NV were enriched in pathways of inflammation and damage-repair-related functions. Mass spectrometry analysis showed that UCMSC-NV encapsulated functional proteins that may achieve therapeutic effect equally as good as UCMSC-Exo. Conclusions: UCMSC-NV are more efficacious and can be obtained at a higher yield than UCMSC-Exo and are a promising therapeutic strategy to improve wound healing in diabetes patients.