Regenerative Cell and Cell-Free Therapies for Necrotizing Enterocolitis: Progress Toward Clinical Translation

Area of Science:

• Regenerative Medicine
• Neonatal Research
• Gastroenterology

Background:

• Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in premature infants with high mortality and no targeted therapies.
• Current treatment options for NEC are limited, highlighting the need for novel therapeutic strategies.

Purpose of the Study:

• To review preclinical and translational evidence for stem cell and extracellular vesicle (EV)-based regenerative therapies for NEC.
• To identify key steps for the clinical translation of these promising therapies.

Main Methods:

• A narrative review of preclinical studies, systematic reviews, meta-analyses, and early-phase clinical trial data.
• Evidence was synthesized across various stem cell types (MSCs, AFSCs, etc.) and their derived EVs.
• Mechanistic, translational, safety, and ethical considerations were analyzed.

Main Results:

• Multiple stem cell types demonstrated consistent reduction in NEC incidence, severity, and mortality in experimental models.
• Protective effects involve epithelial reinforcement, Wnt/β-catenin activation, immunomodulation, and angiogenesis.
• Cell-free EV strategies showed comparable benefits with improved manufacturing and safety profiles; early trials in other neonatal conditions suggest tolerability.

Conclusions:

• Regenerative cell and cell-free therapies offer a compelling disease-modifying approach for NEC.
• Advancement requires standardized characterization, optimized protocols, large-animal validation, and rigorous clinical trials.
• Careful attention to safety, ethics, and regulatory frameworks is crucial for clinical translation.