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

Abstract

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.

Keywords

• extrusion
• nano‐vesicles
• umbilical cord mesenchymal stem cells
• wound healing