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

Abstract

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.

Figure 1

Specialized proresolving lipid mediator biosynthetic pathways. Main biosynthetic routes, key enzymes, and structures are illustrated (see text for details).

Figure 2

Specialized proresolving lipid mediator (SPM) biosynthesis and bioactions in stem cells (SCs). Direct evidence of SPM biosyntheis has been so far obtained in human periodontal ligament stem cells (hPDLSC) and in mouse bone marrow mesenchymal stromal cells (BM‐MSC) preconditioned with carbon monoxide (CO) in the presence of arachidonic acid or docosahexaenoic acid, as well as coincubated with alveolar epithelial cells. In these last models, SPMs generated by SCs exerted protective actions on organ injury, thus promoting mice survival, bacterial clearance, and inflammation resolution. Direct SPM modulation of SCs functions was observed in mouse and human BM‐MSC, mouse neural stem cells, mouse embryonic stem cells, hPDLSC, and SCs of the human dental apical papilla (SCAP) where LXA₄ stimulated proliferation, migration, and wound healing capacity, while reducing chemokine and growth factor secretion.

Figure 3

Scheme of specialized proresolving lipid mediator (SPM) involvement in stem cells (SCs) pathobiology. SPM binding to its cognate receptor expressed by SCs (top‐left) in conjunction with SPM generation by SCs (top‐right) can regulate SC‐governed pathways involved in immunoregulation, inflammation resolution, and tissue repair through interactions with blood as well as resident cells (center).