Enteric Neural Precursor Cells (ENPC) in the Human Gut

Gastrointestinal Dysmotility Clinical Trial

Official title:

Enteric Neural Precursor Cells (ENPC) in the Human Gut - Identification of Molecular Signature and Characterization of Their Proliferative & Neurogenic Potential Using Surgical/Endoscopic Biopsies in Vitro

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04880538
• Other study ID #: IRB00146589
• Status: Completed
• Start date: April 26, 2021
• Est. completion date: September 11, 2023

Study information

• Verified date: March 2024
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The study aim is to acquire human tissues to (a) understand the structure and organization of the human Enteric Nervous System; (b) perform a molecular transcriptomic profile of individual cells residing in the human gut; (c) study the turnover rates of individual cell types by Fluorescence-activated cell sorting-aided C14 dating of cells; and finally (d) culture the human gut-derived cells characterize the human adult enteric neural stem cell and study its potential for Neuro-glial differentiation. This study will advance our knowledge of the the cellular and molecular correlates of changes in the Enteric Nervous System that are associated with disorders of motility.

Description:

(i) To study the structure and organization of the human Enteric Nervous System by tissue clarification, immunofluorescence, and 2-photon and light-sheet microscopy. (ii) To find out the molecular signature that defines various gastrointestinal cells that include the neurons, glia, precursor cells within the Enteric Nervous System and cells associated with the Enteric Nervous System, such as Interstitial Cell of Cajal and macrophages in the human whole gut surgical resection and full thickness endoscopic resection-derived tissues using single cell RNA sequencing and analyses. (iii) To isolate these cells and study their proliferative and neurogenic potential in vitro and on transplantation into the gut tissue of immunodeficient mice. (iv) To time stamp and determine the age of Enteric Nervous System cells in adults and determine whether different enteric disease states alter the cycling times of these cells. (v) To use gut specimens derived from surgical resections and full thickness endoscopic resection-derived tissues for 1. Generating ex vivo preps to study and understand the electrophysiological properties of the gut wall and 2. Generating cultured ex vivo preps to understand the interaction between enteric extracellular matrix and cells of the Enteric Nervous System.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: September 11, 2023
• Est. primary completion date: September 11, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• English speaking patients in the age range 18 - 100.
• Patients suffering from Irritable Bowel Syndrome, Inflammatory Bowel Disease, Diabetes, Gastroparesis, will be included.
• Patients suffering from Collagen disorders such as Alport Syndrome, Ehlers-Danlos Syndrome, Goodpasture Syndrome.
• Patients suffering from plexiform neurofibromas.
• Patients with bariatric surgery.
• Patients with appendicitis.
• Patients with scleroderma.

Exclusion Criteria:

• Patients suffering from HIV, Hepatitis C, and other infectious diseases that require the handling of tissues in a Bio-safety level 3 environment.
• Patients suffering from infectious enteric disorders.
• Patients without any Gastrointestinal disorders (i.e. healthy volunteers).

Related Conditions & MeSH terms

• Gastrointestinal Dysmotility

Intervention

Procedure:
• Endoscopic procedure
Endoscopic biopsy of one or more of the following: esophagus, stomach, small bowel, colon, or rectum as part of patient clinical care. Biopsies will be performed during endoscopy or colonoscopy and will be transported to the research laboratory for evaluation.

Locations

Country	Name	City	State
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Visualization of the network of Nestin+ cells in human gut resection specimens.	Presence or absence of antibodies (including but not limited to) specific to Nestin, p75 neurotrophin receptor, pan-neuronal antibodies, pan-glial antibodies, antibodies against Interstitial Cells of Cajal.	Up to one year