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

Sponsor
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study ID
NCT07721207
Status
Not Yet Recruiting

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Conditions

  • Inflammatory Bowel Diseases

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

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.

Study Details

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.

Key Dates

First listed
Jul 22, 2026
Start date
Nov 1, 2026
Status verified
Jul 2026
Primary completion
Nov 1, 2027
Completion
Dec 1, 2027

Study Design

Enrollment
40 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE

Arms

  • Other: hAMSC secretome-treated samples
    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.

Primary Outcome Measure

Ex vivo modulation of immune cell populations by hAMSC-derived secretome [ Time Frame: Ex vivo assessment performed within 7 days of sample collection. ]

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