Novel Lipid Mediator 7,14-docosahexaenoic Acid: Biogenesis and Harnessing Mesenchymal Stem Cells to Ameliorate Diabetic Mellitus and Retinal Pericyte Loss

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2024 Mar 27

PMID 38533089

Authors

Yan Lu

Haibin Tian

Hongying Peng

Quansheng Wang

Bruce A Bunnell

Nicolas G Bazan

Song Hong

Affiliations

Soon will be listed here.

Abstract

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 7,14-dihydroxy-4,8,10,12,16,19-docosahexaenoic acid (7,14-diHDHA), a maresin-1 stereoisomer biosynthesized by leukocytes and related enzymes. Moreover, 7,14-diHDHA can enhance mesenchymal stem cell (MSC) functions in the amelioration of diabetic mellitus and retinal pericyte loss in diabetic mice. MSCs treated with 7,14-diHDHA were delivered into mice every 5 days for 35 days. Blood glucose levels in diabetic mice were lowered by 7,14-diHDHA-treated MSCs compared to control and untreated MSC groups, accompanied by improved glucose tolerance and higher blood insulin levels. 7,14-diHDHA-treated MSCs increased insulin β-cell ratio and decreased glucogan α-cell ratio in islets, as well as reduced macrophages in pancreas. 7,14-diHDHA induced MSC functions in promoting MIN6 β-cell viability and insulin secretion. 7,14-diHDHA induced MSC paracrine functions by increasing the generation of hepatocyte growth factor and vascular endothelial growth factor. Furthermore, 7,14-diHDHA enhanced MSC functions to ameliorate diabetes-caused pericyte loss in diabetic retinopathy by increasing their density in retina in mice. Our findings provide a novel strategy for improving therapy for diabetes and diabetic retinopathy using 7,14-diHDHA-primed MSCs.

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