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Novel Lipid Mediator 7S,14R-Docosahexaenoic Acid: Biogenesis and Harnessing Mesenchymal Stem Cells to Ameliorate Diabetic Mellitus and Retinal Pericyte Loss
Lu, Y.; Tian, H.; Peng, H.; Wang, Q.; Bunnell, B.A.; Bazan, N.G.; Hong, S. Novel Lipid Mediator 7S,14R-Docosahexaenoic Acid: Biogenesis and Harnessing Mesenchymal Stem Cells to Ameliorate Diabetic Mellitus and Retinal Pericyte Loss. Frontiers in Cell and Developmental Biology 2024, 12, doi:10.3389/fcell.2024.1380059.
Lu, Y.; Tian, H.; Peng, H.; Wang, Q.; Bunnell, B.A.; Bazan, N.G.; Hong, S. Novel Lipid Mediator 7S,14R-Docosahexaenoic Acid: Biogenesis and Harnessing Mesenchymal Stem Cells to Ameliorate Diabetic Mellitus and Retinal Pericyte Loss. Frontiers in Cell and Developmental Biology 2024, 12, doi:10.3389/fcell.2024.1380059.
Lu, Y.; Tian, H.; Peng, H.; Wang, Q.; Bunnell, B.A.; Bazan, N.G.; Hong, S. Novel Lipid Mediator 7S,14R-Docosahexaenoic Acid: Biogenesis and Harnessing Mesenchymal Stem Cells to Ameliorate Diabetic Mellitus and Retinal Pericyte Loss. Frontiers in Cell and Developmental Biology 2024, 12, doi:10.3389/fcell.2024.1380059.
Lu, Y.; Tian, H.; Peng, H.; Wang, Q.; Bunnell, B.A.; Bazan, N.G.; Hong, S. Novel Lipid Mediator 7S,14R-Docosahexaenoic Acid: Biogenesis and Harnessing Mesenchymal Stem Cells to Ameliorate Diabetic Mellitus and Retinal Pericyte Loss. Frontiers in Cell and Developmental Biology 2024, 12, doi:10.3389/fcell.2024.1380059.
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 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. MSCs treated with 7S,14R-diHDHA were delivered into db/db mice i.v. every 5 days for 35 days. 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+ β-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 β-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. Our findings provide a novel strategy for improving therapy for diabetes and diabetic retinopathy using 7S,14R-diHDHA-primed MSCs.
Keywords
diabetic mellitus and complications; mesenchymal stem cell; 7S,14R-diHDHA; db/db mice; blood glucose level; β-cell and α-cell; macrophage; insulin; pancreas and islets; retinopathy
Subject
Medicine and Pharmacology, Medicine and Pharmacology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
