The administration of amnion-derived multipotent cell secretome ST266 protects against necrotizing enterocolitis in mice and piglets

Chhinder P. Sodhi, Raheel Ahmad, Hongpeng Jia, William B. Fulton, Carla Lopez, Andres J. Gonzalez Salazar, Asuka Ishiyama, Maame Sampah, Steve Steinway, Sanxia Wang, Thomas Prindle, Menghan Wang, David L. Steed, Howard Wessel, Ziv Kirshner, Larry R. Brown, Peng Lu, David J. Hackam

Research output: Contribution to journalArticlepeer-review


Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in premature infants and is steadily rising in frequency. Patients who develop NEC have a very high mortality, illustrating the importance of developing novel prevention or treatment approaches. We and others have shown that NEC arises in part from exaggerated signaling via the bacterial receptor, Toll-like receptor 4 (TLR4) on the intestinal epithelium, leading to widespread intestinal inflammation and intestinal ischemia. Strategies that limit the extent of TLR4 signaling, including the administration of amniotic fluid, can reduce NEC development in mouse and piglet models. We now seek to test the hypothesis that a secretome derived from amnion-derived cells can prevent or treat NEC in preclinical models of this disease via a process involving TLR4 inhibition. In support of this hypothesis, we show that the administration of this secretome, named ST266, to mice or piglets can prevent and treat experimental NEC. The protective effects of ST266 occurred in the presence of marked TLR4 inhibition in the intestinal epithelium of cultured epithelial cells, intestinal organoids, and human intestinal samples ex vivo, independent of epidermal growth factor. Strikingly, RNAseq analysis of the intestinal epithelium in mice reveals that the ST266 upregulates critical genes associated with gut remodeling, intestinal immunity, gut differentiation. and energy metabolism. These findings show that the amnion-derived secretome ST266 can prevent and treat NEC, suggesting the possibility of novel therapeutic approaches for patients with this devastating disease.

Original languageEnglish (US)
Pages (from-to)G265-G282
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number3
StatePublished - Sep 2022


  • RNAseq
  • Toll-like receptor 4
  • enterocyte
  • intestinal transcriptome
  • necrotizing enterocolitis

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology


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