Ex Vivo Study of hAMSC Secretome in Inflammatory Bowel Disease: Effects on Inflammation and Fibrosis (TARGET)

NCT07721207 | Not Yet Recruiting

• 1 other identifier: TARGET 27622
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

Inflammatory Bowel Diseases (IBD), including ulcerative colitis and Crohn's disease, are chronic immune-mediated disorders characterized by relapsing gastrointestinal inflammation driven by genetic, immune, microbial, and environmental factors. Despite advances in biologic therapies and small molecules, a substantial proportion of patients exhibit incomplete response, loss of response over time, or progression toward structural bowel damage, including fibrosis, for which no approved anti-fibrotic therapies are currently available. Current treatments mainly target single inflammatory pathways and are insufficient to restore the complex immune, epithelial, and stromal network dysfunction underlying disease persistence and progression, particularly in refractory disease and fibrostenotic Crohn's disease. This study investigates the ex vivo effects of human amniotic mesenchymal stromal cell (hAMSC)-derived secretome, a cell-free biologic product containing bioactive mediators and extracellular vesicles with immunomodulatory, anti-inflammatory, anti-fibrotic, and pro-regenerative properties. The secretome is hypothesized to modulate immune responses, epithelial barrier integrity, mucosal repair, and fibrotic pathways simultaneously. Preliminary data in peripheral blood mononuclear cells (PBMCs) show reduced T helper 1 (Th1) polarization with decreased interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α), and increased regulatory T cells (FOXP3+). Ex vivo experiments in Crohn's disease biopsies indicate a shift toward a more tolerogenic and reparative cytokine profile. This monocentric translational study includes 40 adult patients (≥18 years) with confirmed IBD, stratified into four clinical subgroups based on disease activity, treatment exposure, and fibrostenotic phenotype. Intestinal biopsies and PBMCs are collected prospectively and analyzed within 7 days of sampling. The primary objective is to evaluate ex vivo modulation of inflammatory, immune, epithelial, and fibrotic pathways after exposure to hAMSC secretome. Secondary objectives include assessment of fibrosis markers (COL1A1, ACTA2), epithelial barrier proteins (claudin-1, claudin-2, MUC2), barrier function (TEER), and molecular pathway changes using patient-derived organoids and co-culture systems under basal and pro-fibrotic conditions. The study duration is 36 months, including sample collection, laboratory experiments, multi-omics analyses, and data integration.

Conditions

Inflammatory Bowel Diseases

Outcome Measures

Primary Outcomes (3)

• Ex vivo modulation of immune cell populations by hAMSC-derived secretome

  Frequency and activation status of T helper 1 (Th1), T helper 17 (Th17), regulatory T cells (Treg), and innate immune populations in patient-derived intestinal biopsies and peripheral blood mononuclear cells (PBMCs) after ex vivo exposure to hAMSC-derived secretome, assessed by multicolor flow cytometry.

  Ex vivo assessment performed within 7 days of sample collection.

• Ex vivo modulation of inflammatory cytokines by hAMSC-derived secretome

  Levels of key inflammatory and regulatory cytokines, including tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin 6 (IL-6), and interleukin 10 (IL-10), in supernatants of patient-derived intestinal biopsies and PBMCs after ex vivo exposure to hAMSC-derived secretome, assessed by multiplex cytokine assays.

  Ex vivo assessment performed within 7 days of sample collection.

• Ex vivo modulation of fibrosis- and mucosal repair-related markers by hAMSC-derived secretome.

  Molecular analysis of fibrosis- and mucosal repair-related markers expression in patient-derived intestinal biopsies and PBMCs after ex vivo exposure to hAMSC-derived secretome.

  Ex vivo assessment performed within 7 days of sample collection.

Secondary Outcomes (3)

• Intestinal epithelial barrier integrity and function

  Ex vivo analysis within 7 days of treatment

• Transcriptomic and spatial omics profiling of immune-epithelial-fibrotic niche

  Within study period (months 6-30)

• Immune-epithelial cross-talk modulation

  Ex vivo analysis within 7 days of treatment

Study Arms (1)

hAMSC secretome-treated samples

OTHER

Ex vivo treatment of patient-derived intestinal biopsies, peripheral blood mononuclear cells (PBMCs), and organoid co-culture systems with human amniotic mesenchymal stromal cell (hAMSC)-derived secretome.

Biological: Human amniotic mesenchymal stromal cell (hAMSC)-derived secretome

Interventions

Human amniotic mesenchymal stromal cell (hAMSC)-derived secretome BIOLOGICAL

Ex vivo exposure of patient-derived intestinal biopsies, peripheral blood mononuclear cells (PBMCs), and intestinal organoid co-culture systems to human amniotic mesenchymal stromal cell (hAMSC)-derived secretome. The secretome consists of bioactive soluble factors and extracellular vesicles evaluated for immunomodulatory, anti-inflammatory, anti-fibrotic, and pro-regenerative effects on immune, epithelial, and stromal pathways.

Also known as: amniotic MSC secretome, mesenchymal stromal cell secretome, conditioned medium hAMSC, extracellular vesicles hAMSC

hAMSC secretome-treated samples

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Confirmed diagnosis of inflammatory bowel disease (IBD), including Crohn's disease or ulcerative colitis
• Classification into one of the predefined clinical subgroups (remission, active treatment-naïve disease, refractory disease defined as failure of ≥2 lines of therapy, or fibrostenotic Crohn's disease phenotype)
• Availability of intestinal biopsies and/or peripheral blood mononuclear cells (PBMCs) for ex vivo analyses
• Written informed consent for collection, storage, and use of biological samples for research purposes, in accordance with the Declaration of Helsinki and local Ethics Committee approval

You may not qualify if:

• Age \< 18 years
• Presence of systemic diseases not related to inflammatory bowel disease (IBD) that may interfere with immunological or molecular analyses
• Inadequate or unavailable biological material for ex vivo experiments, including inability to generate patient-derived intestinal organoids

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Ex vivo translational study using patient-derived intestinal biopsies, peripheral blood mononuclear cells, and organoid co-culture systems treated with human amniotic mesenchymal stromal cell (hAMSC)-derived secretome.

Study Record Dates

• First Submitted: July 1, 2026
• First Posted: July 22, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 22, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share