Gastrointestinal Dysmotility
Conditions
Brief 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.
Detailed 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.
Interventions
PROCEDUREEndoscopic 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.
Sponsors
Johns Hopkins University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Visualization of the network of Nestin+ cells in human gut resection specimens. | Up to one year | 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. |
Countries
United States
Outcome results
None listed