Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Planar culture of gastrointestinal stem cells for screening pharmaceuticals for adverse event risk

Award Number: R43TR004230
ORGANIZATION: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2023

Group Awards By:

View Award Description

Planar culture of gastrointestinal stem cells for screening pharmaceuticals for adverse event risk - Project Summary GI side effects, such as ulcers and diarrhea, represent the most common source of adverse events for pharmaceuticals. GI stem cells are responsible for repairing and replenishing GI epithelium, and pharmaceutical inhibition of these functions likely contribute to adverse event risk. Currently there are no high-throughput and cost-effective means of screening candidate therapeutics for effects on GI stem cells. Animal models are fraught with confounds (e.g., rats generally do not exhibit diarrhea until death is imminent) and current in vitro models like the Caco-2 tumor cell line do not include a normal stem cell population. While 3D-organoid cultures have a stem cell component, access to the apical aspect of the monolayer for compound exposure is not possible without low-throughput microinjection. Altis Biosystems, Inc. has developed a proprietary culture platform, RepliGut® Planar, enabling primary human GI cells to form an epithelium for drug screening. In preliminary efforts, we initiated development of a GI stem cell-specific platform called RepliGut® StemScreen to address the unmet need for high-throughput, cost-effective GI stem cell screening, including a range of assays to measure properties that might lead to adverse events. These include assays for proliferation using S-phase staining and assessing downstream differentiation and ability to establish barrier function via non-destructive transepithelial electric resistance (TEER) analysis. A panel of pharmaceutical agents associated with clinically adverse GI side effects, tested in a classic EdU assay using StemScreen planar cultures, demonstrated dose-dependent inhibition of stem cell proliferation and prevented stem cell differentiation into a mature epithelium with barrier function. During Phase I we will: 1) characterize monolayer proliferation properties of donor cells in the Altis biobank(initially transverse colon stem cells will be evaluated, with other regions tested in Phase II) from three donors and 2) test a selection of therapeutic agents with known GI adverse event risks for effects on stem cell proliferation, impacting differentiation and the formation of a functional epithelial barrier (indexed as TEER). Demonstrating that the StemScreen platform provides an in vitro screening tool capable of predicting a drug’s risk for GI adverse events in Phase I will enable deeper characterization of stemness, stem cells from other GI regions (e.g., ascending and descending colon; small intestine regions including jejunum, etc.), and stem cell phenotypes. In Phase 2, we plan externally validate the platform in collaboration with leading industry laboratories prior to commercial launch.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	ALTIS BIOSYSTEMS, INC.	6 DAVIS DR	DURHAM	NC	27709	DURHAM	USA	National Center for Advancing Translational Sciences	000	1	2/23/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $256,574 )
2022	2022	ALTIS BIOSYSTEMS, INC.	6 DAVIS DR	DURHAM	NC	27709	DURHAM	USA	National Center for Advancing Translational Sciences	000	1	6/23/2022	NEW	$256,574
														Subtotal = $256,574

Grand Total All Awards = $256,574

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Planar culture of gastrointestinal stem cells for screening pharmaceuticals for adverse event risk

Award Number: R43TR004230

ORGANIZATION: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2023

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer