Fig. 2
From: Stem cell therapy as a promising strategy in necrotizing enterocolitis
The different types of stem cells used to treat NEC and their signaling pathways. Stem cells exert NEC therapeutic effects via various signaling pathways. Mainly, MSCs exert therapeutic effects through paracrine signaling. In addition, BM-MSCs inhibit prolyl hydroxylase 2 to promote nuclear factor-κB activation and increase the release of the intestinal protective factors. UC-MSCs activate endothelial nitric oxide synthase and secrete hydrogen sulfide in NEC therapy. NSCs can repair and replenish neurons in the ENS, activate the neuronal nitric oxide synthase to prevent the ENS from being damaged, and preserve intestinal integrity. AF-MSCs activate ER stress response to process the unfolded tight junction proteins and promote the expression of Bcl-2/Bax gene. Moreover, AF-MSCs increase the expression of COX-2 in the lamina propria. AF-MSCs and P-MSCs restore the ISC niche to promote IECs proliferation with increased Wnt/β-catenin signaling. ISCs are deservedly responsible for the differentiation to IECs via various signaling pathways. BM-MSCs bone marrow-derived mesenchymal stem cells; UC-MSCs umbilical cord-derived stem cells; NSCs neural stem cells; ENS enteric neural system; COX-2 cyclooxygenase 2; Bcl-2 B-cell lymphoma 2; Bax Bcl-2-associated X protein; AF-MSCs amniotic fluid-derived mesenchymal stem cells; ISCs intestinal stem cells; P-MSCs placental-derived mesenchymal stem cells