Tissue Modeling in Systemic Sclerosis Using Induced Pluripotent Stem Cells (iPSCs)

NCT07650565 | Not Yet Recruiting

• 2 other identifiers: RECHMPL24_02782025-A02898-41
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of the study is to establish an in vitro model using iPSCs to test the hypotheses developed. The primary objective is to generate, via the SAFE-IPS platform, 8 iPSC lines derived from blood samples taken from:

• Two patients with severe/diffuse SSc with multi-organ involvement (with anti-SCl-70 autoantibodies)
• Two of their healthy close relatives
• Two patients with uncomplicated SSc with localized involvement (with non-SCl-70 autoantibodies)
• Two of their healthy close relatives These 8 cell lines will be differentiated by several teams at the FHU REGENHAB into:
• Immune cells (monocytes/macrophages, neutrophils, dendritic cells, B/T lymphocytes)
• Mesenchymal stromal cells
• Myocardial cells
• Skin cells (fibroblasts)
• Synovial cells
• Bronchial cells
• Endothelial cells This project aims to map cellular and tissue heterogeneity using iPSC lines obtained from patients with both severe and mild SSc, employing single-cell RNA-seq under various pathological conditions, with and without autologous (or even heterologous) autoimmune stimulation. For example, the percentages of different cell types comprising a tissue in these various situations will be calculated. Comparisons will be made with control groups using healthy iPSC lines by recruiting healthy subjects with the same genetic profile and gender as the patients.

Conditions

Systemic Sclerosis (SSc)

Keywords

Systemic Sclerosis; Induced Pluripotent Stem Cells; Autoimmune Disease; Tissue Modeling

Outcome Measures

Primary Outcomes (4)

• Rate of successful iPSC line generation from PBMCs in diffuse/severe systemic sclerosis patients

  Percentage of participants with diffuse/severe systemic sclerosis (anti-Scl-70 positive) from whom at least one iPSC line is successfully generated via Sendai virus reprogramming of peripheral blood mononuclear cells (PBMCs). Unit of Measure: % of participants with at least one validated iPSC line

  At inclusion (Day 0 blood draw; iPSC generation assessed within approximately 3 months post-collection)

• Rate of successful differentiation of iPSCs into at least one target functional cell type in localized/non-complicated systemic sclerosis patients

  Among validated iPSC lines from localized/non-complicated SSc patients, the percentage of lines achieving successful directed differentiation into at least one target cell type (cardiomyocytes, macrophages, bronchial epithelial cells, immune cells, or fibroblasts). Success is confirmed by cell-type-specific marker expression assessed by immunofluorescence and flow cytometry. Unit of Measure: % of validated iPSC lines successfully differentiated into ≥1 target cell type

  At inclusion (assessed within approximately 6 months post-collection)

• Rate of successful iPSC line generation from PBMCs in localized/non-complicated systemic sclerosis patients

  Percentage of participants with localized/non-complicated systemic sclerosis (anti-Scl-70 negative, other SSc-specific antibody positive) from whom at least one iPSC line is successfully generated via Sendai virus reprogramming of PBMCs. Unit of Measure: % of participants with at least one validated iPSC line

  At inclusion (Day 0 blood draw; iPSC generation assessed within approximately 3 months post-collection)

• Rate of successful differentiation of iPSCs into at least one target functional cell type in diffuse/severe systemic sclerosis patients

  Among validated iPSC lines from diffuse/severe SSc patients, the percentage of lines achieving successful directed differentiation into at least one target cell type (cardiomyocytes, macrophages, bronchial epithelial cells, immune cells, or fibroblasts). Success is confirmed by cell-type-specific marker expression assessed by immunofluorescence and flow cytometry (e.g., cTnT for cardiomyocytes; CD68/CSFR1 for macrophages; NKX2.1/MUC5AC for bronchial epithelium). Unit of Measure: % of validated iPSC lines successfully differentiated into ≥1 target cell type

  At inclusion (assessed within approximately 6 months post-collection)

Secondary Outcomes (9)

• Change in cardiomyocyte differentiation efficiency following autologous autoantibody exposure

  At inclusion

• Change in macrophage differentiation and inflammatory cytokine secretion following autologous autoantibody exposure

  At inclusion

• Functional characterization of iPSC-derived cardiomyocytes - spontaneous beating activity

  At inclusion

• Molecular characterization of iPSC-derived cardiomyocytes - cardiac marker expression

  At inclusion

• Phenotypic characterization of iPSC-derived macrophages - pan-macrophage surface marker expression

  At inclusion

Study Arms (1)

Participants with Systemic Sclerosis and Healthy Controls

EXPERIMENTAL

Participants undergo blood sample collection for generation of induced pluripotent stem cells (iPSCs) and in vitro cellular and tissue modeling.

Procedure: Blood Sample Collection

Interventions

Blood Sample Collection PROCEDURE

Collection of approximately 28 mL of blood from each participant to generate induced pluripotent stem cell (iPSC) lines for in vitro cellular and tissue modeling analyses.

Participants with Systemic Sclerosis and Healthy Controls

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 85 years
• Diagnostic criteria for the three groups:
• \> Severe SSc group:
• Diagnosis of diffuse/severe systemic sclerosis by a physician for at least 12 months based on recommendations (according to ACR criteria)
• Known positivity of autoimmunity directed against Scl-70
• \> Localized/non-complicated SSc group:
• Diagnosis of systemic sclerosis by a physician for at least 12 months based on recommendations (according to ACR criteria)
• Documentation of the absence of major vital organ involvement
• Negative anti-Scl-70 autoantibodies but presence of other systemic sclerosis-related autoantibodies
• \> Healthy subjects group:
• First-degree relative of a patient recruited in one of the systemic sclerosis groups (father, mother, brother, sister, adult child)
• Absence of systemic autoimmune diseases

You may not qualify if:

• Other diseases that may affect erythroid progenitor cells (non-exhaustive: active cancer, hematological malignancy, chemotherapy targeting DNA)
• Protected populations according to French public health law (pregnant or breastfeeding women; individuals deprived of liberty by judicial or administrative decision; adults under legal protection (any form of guardianship))
• Absence of informed consent
• Not affiliated with a national health insurance system

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

University hospital Montpellier

Montpellier, France

Location

MeSH Terms

Conditions

Scleroderma, Systemic; Autoimmune Diseases

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Immune System Diseases

Study Officials

• ARNAUD BOURDIN, MD

  University Hospital, Montpellier

  STUDY DIRECTOR

Central Study Contacts

ARNAUD BOURDIN, MD

CONTACT

04 67 33 61 26; a-bourdin@chu-montpellier.fr

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: Single group study in which participants undergo a blood sample collection for the generation of induced pluripotent stem cells (iPSCs) and subsequent in vitro cellular and tissue modeling analyses

Study Record Dates

• First Submitted: May 18, 2026
• First Posted: June 16, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: June 16, 2026

Record last verified: 2026-06

Locations

FR (1)