Proresolving Lipid Mediators and Receptors in Stem Cell Biology: Concise Review

Abstract

Summary Accumulating evidence indicates that stem cells (SCs) possess immunomodulatory, anti‐inflammatory, and prohealing properties. The mechanisms underlying these functions are being investigated with the final goal to set a solid background for the clinical use of SCs and/or their derivatives. Specialized proresolving lipid mediators (SPMs) are small lipids formed by the enzymatic metabolism of polyunsaturated fatty acids. They represent a leading class of molecules that actively and timely regulate the resolution of inflammation and promote tissue/organ repair. SC formation of these mediators as well as expression of their receptors has been recently reported, suggesting that SPMs may be involved in the immunomodulatory, proresolving functions of SCs. In the present review, we summarize the current knowledge on SPMs in SCs, focusing on biosynthetic pathways, receptors, and bioactions, with the intent to provide an integrated view of SPM impact on SC biology. Stem Cells Translational Medicine 2019;8:992–998

Could Arachidonic Acid-Derived Pro-Resolving Mediators Be a New Therapeutic Strategy for Asthma Therapy?

“…Thus, catabolization and antagonization of pro-inflammatory mediators, a decrease in leukocyte numbers at inflammatory sites, and tissue repair are key events in the resolution process ( 13 ). It is notewothy that different from classical anti‐inflammatory molecules, the SPMs modulate the end of the inflammatory response, without promoting unwanted immunosuppression ( 15 ). During the resolution phase, leukocyte apoptosis and metabolization of intracellular inflammatory signals lead to the clearance of inflammatory cells by specialized phagocytes.…”

“…These endogenous mediators are biosynthesized in local inflamed tissue microenvironments, and can control the magnitude/duration of the inflammatory response as well as the timing of tissue restoration ( 17 ). They primarily come from the metabolism of polyunsaturated fatty acids, such as AA, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA) ( 15 ). Interestingly, several AA-derived mediators have consistently presented pro-resolving and tissue protecting activities in asthma ( 24 , 25 ).…”

Resolvin D1 supports skeletal myofiber regeneration via actions on myeloid and muscle stem cells

“…These autocoids actively limit PMN influx, while simultaneously stimulating macrophage functions essential for timely resolution of inflammation (8). Emerging evidence suggests that SPMs can also exert important biological actions on nonimmune cell populations (e.g., stem cells) that may contribute to their physiological effects (9).…”

Roles of Specialized Pro-Resolving Lipid Mediators in Autophagy and Inflammation

“…Despite Formyl peptide receptor 2 (ALX/FPR2, also termed FPR2, FPRL1, or FPR2/ALX) being the first discovered and the most studied SPM receptor able to convey LXA 4 bioactions in PMNs [72], it is now clear that this receptor is expressed in multiple cell types including myeloid cells and lymphocytes, resident endothelial, epithelial cells, fibroblasts [73], and stem cells [74], and is also activated by other SPMs (RvD1, AT-RvD1, RvD3, AT-RvD3, and AT-LXA 4 ) [69,[75][76][77][78]. In addition, in vitro studies showed that ALX/FPR2 is a promiscuous receptor that is also recognized and stimulated by a variety of natural and synthetic peptides to translate effects ranging from pro-inflammatory to anti-inflammatory and pro-resolution depending on the activating ligand (reviewed in [79]).…”