Amniotic fluid stem cell attenuated necrotizing enterocolitis progression by promoting Rspo3/AMPKα axis

Area of Science:

• Gastroenterology
• Stem Cell Therapy
• Molecular Biology

Background:

• Necrotizing enterocolitis (NEC) is a severe intestinal disease in neonates.
• Intestinal epithelial cell differentiation is critical in NEC pathogenesis.
• R-spondin 3 (Rspo3) plays a role in cellular processes and intestinal development.

Purpose of the Study:

• To investigate the role and mechanism of Rspo3 in NEC.
• To determine if amniotic fluid stem cells (AFSCs) therapy impacts NEC via Rspo3.
• To elucidate the Rspo3/AMPKα signaling pathway in NEC.

Main Methods:

• Assessed Rspo3 alteration in NEC patients and LPS-induced in vitro models.
• Conducted gain-of-function assays for Rspo3 in NEC.
• Analyzed adenosine 5'-monophosphate-activated protein kinase α (AMPKα) activation.
• Co-cultured human intestinal epithelial cells (HIECs) with AFSCs.

Main Results:

• Rspo3 expression was significantly reduced in NEC.
• Rspo3 overexpression ameliorated LPS-induced injury, inflammation, and tight junction damage in HIECs.
• Rspo3 overexpression reversed NEC-induced AMPKα inactivation; Compound C blocked this effect.
• AFSCs treatment restored Rspo3 expression and attenuated NEC progression, potentially via exosomes.

Conclusions:

• Rspo3 plays a protective role in NEC pathogenesis.
• AFSCs therapy benefits NEC by restoring Rspo3 expression and activating the Rspo3/AMPKα axis.
• The Rspo3/AMPKα pathway, possibly mediated by exosomes, is a potential therapeutic target for NEC.