# Sulfur Based Stem Cell Therapeutics in Necrotizing Enterocolitis

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $507,107

## Abstract

This investigator's proposal describes a 5-year project designed to study mesenchymal stem cells derived from
inducible pluripotent stem cells as a treatment modality for necrotizing enterocolitis (NEC). NEC is a devastating
intrabdominal emergency in the neonatal population that often requires the surgical resection of intestine, thereby
leaving infants with a suboptimal length of bowel to absorb nutrition. It occurs in roughly 10% of preterm infants,
carries a 40-50% mortality rate, and costs $1.3 billion in medical costs annual. There has been lack of
advancement in treatment modalities over the last decade for NEC, and cellular therapy may provide beneficial
improvements in outcomes. Investigators hypothesize that hydrogen sulfide (H2S) is a key paracrine factor in
mesenchymal stem cell mediated intestinal protection during necrotizing enterocolitis. To more readily study the
effects of hydrogen sulfide, they propose the development of a near infrared H2S specific probe to more
accurately quantify H2S in biological systems. Further proposed studies overexpress hydrogen sulfide producing
enzymes in iPSC derived MSCs and aim to identify the secreted polysulfides which likely serve as intracellular
signaling molecules. Finally, they assess the role of Cys440 on eNOS as a critical residue that interacts with
hydrogen sulfide to promote mesenteric vasodilation and improved clinical outcomes in experimental NEC. The
investigators propose three Specific Aims: 1) To define the role of hydrogen sulfide signaling from MSCs during
cellular therapy for NEC, 2) To develop and validate a hydrogen sulfide probe to effectively measure H2S in
biological systems, and 3) To evaluate the interaction of iPSC derived MSCs, H2S, and Nitric Oxide (NO) on the
mesenteric endothelium during experimental NEC.
The investigator is a pediatric surgeon scientist who was formally funded through the NIDDK as a K08 awardee.
This grant support expired in May 2022. He is now seeking out his first R01 award as an Early Stage Investigator.
His career goals are to use this R01 to further develop cellular therapy as a viable treatment for necrotizing
enterocolitis. Dr. Markel has a long standing collaborative and mentor relationship with Dr. Ken Olson at Notre
Dame/IU Southbend. He is an international expert in hydrogen sulfide signaling and will continue to assist Dr.
Markel with assays designed to further quantify the secreted polysulfide pool. Dr. Markel has also collaborated
with Dr Ben Gaston at his local institution who is an expert on nitric oxide signaling, as well as Dr. Tim Lescun,
a large animal veterinarian at Purdue University, who has assisted in establishing a piglet model of NEC in Dr.
Markel's laboratory.
In summary, this research aims to understand the mechanism that iPSC derived MSCs use to provide
protection in NEC. The proposal is highly innovative and the investigator has the appropriate support,
collaborations, and infrastructure in place to carry out the stud...

## Key facts

- **NIH application ID:** 10827977
- **Project number:** 5R01DK133418-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** TROY A MARKEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $507,107
- **Award type:** 5
- **Project period:** 2023-04-15 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10827977

## Citation

> US National Institutes of Health, RePORTER application 10827977, Sulfur Based Stem Cell Therapeutics in Necrotizing Enterocolitis (5R01DK133418-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10827977. Licensed CC0.

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