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

Harnessing stem cells (SCs) for immunoregulatory and regenerative purposes represents a pivotal goal in SC-related therapeutics. A proper knowledge of SC capability to release and/or respond to agents that promote the resolution of the inflammatory response as well as tissue/organ repair is key to develop innovative approaches, based on SCs, to treat diseases characterized by ongoing unresolved inflammation.