Optogenetic engineered umbilical cord MSC-derived exosomes for remodeling of the immune microenvironment in diabetic wounds and the promotion of tissue repair.
J Nanobiotechnology
; 21(1): 176, 2023 Jun 02.
Article
en En
| MEDLINE
| ID: mdl-37269014
ABSTRACT
BACKGROUND:
Angiogenesis and tissue repair in chronic non-healing diabetic wounds remain critical clinical problems. Engineered MSC-derived exosomes have significant potential for the promotion of wound healing. Here, we discuss the effects and mechanisms of eNOS-rich umbilical cord MSC exosomes (UCMSC-exo/eNOS) modified by genetic engineering and optogenetic techniques on diabetic chronic wound repair.METHODS:
Umbilical cord mesenchymal stem cells were engineered to express two recombinant proteins. Large amounts of eNOS were loaded into UCMSC-exo using the EXPLOR system under blue light irradiation. The effects of UCMSC-exo/eNOS on the biological functions of fibroblasts and vascular endothelial cells in vitro were evaluated. Full-thickness skin wounds were constructed on the backs of diabetic mice to assess the role of UCMSC-exo/eNOS in vascular neogenesis and the immune microenvironment, and to explore the related molecular mechanisms.RESULTS:
eNOS was substantially enriched in UCMSCs-exo by endogenous cellular activities under blue light irradiation. UCMSC-exo/eNOS significantly improved the biological functions of cells after high-glucose treatment and reduced the expression of inflammatory factors and apoptosis induced by oxidative stress. In vivo, UCMSC-exo/eNOS significantly improved the rate of wound closure and enhanced vascular neogenesis and matrix remodeling in diabetic mice. UCMSC-exo/eNOS also improved the inflammatory profile at the wound site and modulated the associated immune microenvironment, thus significantly promoting tissue repair.CONCLUSION:
This study provides a novel therapeutic strategy based on engineered stem cell-derived exosomes for the promotion of angiogenesis and tissue repair in chronic diabetic wounds.Palabras clave
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Banco de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Experimental
/
Exosomas
Límite:
Animals
Idioma:
En
Año:
2023
Tipo del documento:
Article