Treatment of experimental necrotizing enterocolitis with stem cell-derived exosomes.

ABSTRACT

PURPOSE: Necrotizing enterocolitis (NEC) remains a devastating disease in premature infants. We previously showed that four stem cell (SC) types equivalently improve experimental NEC. Exosomes are intercellular nanovesicles containing RNA, miRNA, DNA, and protein. Because SC therapy faces challenges, our aim was to determine if the beneficial effects of SC are achievable with cell-free exosomes. METHODS: Exosomes from four SC types were compared (1) amniotic fluid-derived mesenchymal SC (AF-MSC); (2) bone marrow-derived MSC (BM-MSC); (3) amniotic fluid-derived neural SC (AF-NSC); and (4) neonatal enteric NSC (E-NSC). Rat pups exposed to NEC received a varying concentration of a single type of exosome with control pups receiving PBS only. Intestinal damage was graded histologically. RESULTS: The incidence of NEC was 0% in unstressed pups and 60.7% in control pups subjected to NEC. Exosomes (4.0×108) reduced NEC incidence to AF-MSC 25.0%; BM-MSC 23.1%; AF-NSC 11.1%; E-NSC 27.3%. When administered at a concentration of at least 4.0×108, all groups demonstrated a significant reduction in NEC compared to untreated pups. At this minimum concentration, there was no difference in treatment efficacy between exosomes and the SC from which they were derived. CONCLUSION: Stem cell-derived exosomes reduce the incidence and severity of experimental NEC as effectively as the stem cells from which they are derived, supporting the potential for novel cell-free exosome therapy for NEC. TYPE OF STUDY Basic science.