The present study confirmed our hypothesis that PHD2 silencing enhances the paracrine efficacy of BM-MSCs on NEC, and demonstrated that PHDMSC-CM, but not MSC-CM, (1) improves survival and promotes the structural and functional restoration of NEC by regulating epithelial regeneration and inflammatory response; (2) activates NF-κB to increase their secretion of pivotal factor IGF-1 and TGF-β2 via binding to IGF-1 and TGF-β2 gene promoter, therefore provides superior therapeutic efficacy on NEC. This evidence concerns the gene TGFB2 and necrotizing enterocolitis.