Novel lipid mediator 7S,14R-docosahexaenoic acid: biogenesis and harnessing mesenchymal stem cells to ameliorate diabetic mellitus and retinal pericyte loss.
Front Cell Dev Biol
; 12: 1380059, 2024.
Article
de En
| MEDLINE
| ID: mdl-38533089
ABSTRACT
Introduction:
Stem cells can be used to treat diabetic mellitus and complications. ω3-docosahexaenoic acid (DHA) derived lipid mediators are inflammation-resolving and protective. This study found novel DHA-derived 7S,14R-dihydroxy-4Z,8E,10Z,12E,16Z,19Z-docosahexaenoic acid (7S,14R-diHDHA), a maresin-1 stereoisomer biosynthesized by leukocytes and related enzymes. Moreover, 7S,14R-diHDHA can enhance mesenchymal stem cell (MSC) functions in the amelioration of diabetic mellitus and retinal pericyte loss in diabetic db/db mice.Methods:
MSCs treated with 7S,14R-diHDHA were delivered into db/db mice i.v. every 5 days for 35 days.Results:
Blood glucose levels in diabetic mice were lowered by 7S,14R-diHDHA-treated MSCs compared to control and untreated MSC groups, accompanied by improved glucose tolerance and higher blood insulin levels. 7S,14R-diHDHA-treated MSCs increased insulin+ ß-cell ratio and decreased glucogan+ α-cell ratio in islets, as well as reduced macrophages in pancreas. 7S,14R-diHDHA induced MSC functions in promoting MIN6 ß-cell viability and insulin secretion. 7S,14R-diHDHA induced MSC paracrine functions by increasing the generation of hepatocyte growth factor and vascular endothelial growth factor. Furthermore, 7S,14R-diHDHA enhanced MSC functions to ameliorate diabetes-caused pericyte loss in diabetic retinopathy by increasing their density in retina in db/db mice.Discussion:
Our findings provide a novel strategy for improving therapy for diabetes and diabetic retinopathy using 7S,14R-diHDHA-primed MSCs.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Langue:
En
Journal:
Front Cell Dev Biol
Année:
2024
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique
Pays de publication:
Suisse