# Developing an optimized cell based platform for assays of the gastrointestinal enteroendocrine system

> **NIH NIH R44** · ALTIS BIOSYSTEMS, INC. · 2020 · $712,990

## Abstract

Project Summary
 The human intestine is a remarkable organ which stores and secretes a variety of hormones
from enteroendocrine (EEC) cells. These hormones play critical roles in regulating human
feeding behavior and satiety, and their dysregulation leads to overeating and a host of other
metabolic disorders. For these reasons, there is a need in the therapeutics marketplace for in
vitro intestinal EEC cell platform that precisely recapitulates the physiology of in vivo intestines.
To meet this need, Altis Biosystems Inc., an early stage biotechnology company, has
collaborated with scientists at academic laboratories to develop a novel, primary-stem-cells-
based, in vitro intestinal model (termed RepliGut). We have finished the SBIR Phase I program
by optimizing the RepliGut platform to enrich enterochromaffin (EC) cells, a subtype of EEC
cells, and increase barrier integrity. We have developed a simple but efficient method that
significantly increases the formation of EEC cells compared with the starting culture conditions.
We have investigated signaling molecules for forced differentiation towards EEC lineage
allocation, quantified assays for serotonin, and investigated passage and donor variation. We
validated the platform with a small-scale compound screen for serotonin secretion from EC
cells. All proposed milestones in the Phase I SBIR were accomplished, thus providing a solid
foundation for this Phase II SBIR application. The focus of this Phase II proposal is to continue
the optimization of EEC formation to meet the market needs for high-throughput screening
assays. Besides EC cells, we will extend our research to the other important subtype,
enteroendocrine L-cells, which secrete GLP-1 and PYY in response to the ingestion of food.
Additional characterizations will be focused on the uniformity of cell behaviors within a 96-well
format. Low well-to-well and plate-to-plate variation will be confirmed before use as a cellular
assay platform. Potential regional-, sex- and age-based variations will be further investigated by
testing stem cells derived from 5 donors and all 6 sections of intestine. The platform will be
validated by screening a large library of metabolic compounds. Performance characteristics of
the platform will then be evaluated in comparisons of our in-house assays vs. kits shipped to
collaborating laboratories.

## Key facts

- **NIH application ID:** 10080388
- **Project number:** 2R44DK121580-02
- **Recipient organization:** ALTIS BIOSYSTEMS, INC.
- **Principal Investigator:** Christopher Eldridge Sims
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $712,990
- **Award type:** 2
- **Project period:** 2019-08-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10080388

## Citation

> US National Institutes of Health, RePORTER application 10080388, Developing an optimized cell based platform for assays of the gastrointestinal enteroendocrine system (2R44DK121580-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10080388. Licensed CC0.

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