Inhibiting hydrogen sulfide production in umbilical stem cells reduces their protective effects during experimental necrotizing enterocolitis.

Abstract:

INTRODUCTION:Umbilical mesenchymal stem cells (USC) have been shown to reduce illness in animal models of necrotizing enterocolitis (NEC), possibly through the paracrine release of hydrogen sulfide (H2S). We hypothesized that animals treated with USCs with inhibited H2S synthesis would exhibit more severe disease. METHODS:NEC was induced in five-day-old mouse pups by formula feeding and hypoxic and hypothermic stress. Experimental groups received intraperitoneal injection of either saline vehicle or 80,000cells/gram of one of the following cell types: USC, USCs with negative-control siRNA, or USCs with targeted siRNA inhibition of the H2S-producing enzymes. Pups were monitored by clinical assessment and after euthanasia, intestine and lung histologic injury were scored. Tissue was homogenized, and concentrations of IL-6, IL-10, and VEGF were determined by ELISA. For statistical analysis, p<0.05 was considered significant. RESULTS:Animals treated with negative-control siRNA USCs were significantly improved compared to vehicle. Clinical sickness scores as well as intestinal and lung histologic injury scores in the targeted siRNA groups were significantly worse when compared to the negative-control siRNA group. IL-6, IL-10, and VEGF had varying patterns of expression in the different groups. CONCLUSION:Inhibition of H2S production in USCs reduces the beneficial effects of these cells during therapy in experimental NEC. LEVEL OF EVIDENCE:Animal studies are typically described as "foundational evidence" without a true level assigned. TYPE OF STUDY:Animal Study.

journal_name

J Pediatr Surg

authors

Drucker NA,Te Winkel JP,Shelley WC,Olson KR,Markel TA

doi

10.1016/j.jpedsurg.2019.02.037

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

1168-1173

issue

6

eissn

0022-3468

issn

1531-5037

pii

S0022-3468(19)30178-2

journal_volume

54

pub_type

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