SAFE-iPS - France's First Hospital-based Platform for the Production of Induced Pluripotent Stem Cells for the Regenerative Medicine of the Future

Background :

Induced pluripotent stem cells (iPSCs) represent a major advance in regenerative medicine because they can be generated from easily accessible autologous somatic cells and differentiated into virtually any cell type. Their potential clinical applications include hematology, neurology, rare diseases, oncology, and regenerative medicine. However, translation of this technology into clinical practice requires Good Manufacturing Practice (GMP)-compliant production processes and stringent quality standards for Advanced Therapy Medicinal Products (ATMPs).

Currently, no French public hospital has a validated and routinely operational GMP platform dedicated to the production of clinical-grade iPSC lines. The SAFE-iPS platform at Montpellier University Hospital combines dedicated clean-room facilities, an ISO 13485-certified quality management system, and more than ten years of expertise in iPSC production and characterization, providing the necessary infrastructure to establish such a platform.

The central hypothesis of the study is that peripheral blood mononuclear cell (PBMC) reprogramming using a non-integrating Sendai viral vector expressing OCT4, KLF4, SOX2 and c-MYC (OKSM) can be successfully implemented in a hospital GMP environment and reproducibly generate clinical-grade iPSC lines fulfilling international quality requirements for future clinical applications.

Objectives :

Primary objective :

The primary objective is to generate, via the SAFE-iPS platform, four clinical-grade iPSC lines derived from peripheral blood samples collected from healthy volunteers:

• Two healthy male volunteers
• Two healthy female volunteers These iPSC lines will be validated according to international pluripotency criteria for future regenerative medicine applications.

Secondary objectives :

Secondary objectives are to:

• Validate genomic safety.
• Evaluate technical reproducibility.
• Evaluate manufacturing efficiency.
• Evaluate the preliminary medico-economic feasibility of the production process.

Study Procedures :

Healthy volunteers will undergo screening, eligibility assessment and peripheral blood collection. Peripheral blood mononuclear cells (PBMCs) will be isolated and reprogrammed using a non-integrating Sendai viral vector under GMP conditions to generate clinical-grade iPSC lines.

The generated cell lines will undergo quality control assessments including evaluation of pluripotency marker expression, genomic stability, absence of residual viral integration, technical reproducibility, manufacturing time and production costs. The study is designed as a prospective, monocentric, open-label, non-comparative pilot feasibility study evaluating the implementation of a hospital-based GMP manufacturing process.

Study Population :

A maximum of six healthy adult volunteers will be enrolled to obtain two validated clinical-grade iPSC lines from male donors and two from female donors. Enrollment will stop once the four clinical-grade iPSC lines meeting international pluripotency criteria have been successfully generated.

Expected Impact :

The SAFE-iPS study is expected to validate the first French public hospital GMP production process dedicated to clinical-grade iPSC manufacturing. The generated data will support future applications for Advanced Therapy Medicinal Products (ATMPs), establish a pilot biobank of clinical-grade iPSC lines, and provide a reproducible organizational and technical model that may subsequently be implemented in other French university hospitals to facilitate the development of regenerative medicine and cell therapy.

Inclusion criteria

• Age ≥ 18 years and ≤ 35 years
• No medical contraindication to a 54 mL blood sample collection
• Negative viral serology for:

• Human Immunodeficiency Virus (HIV)
• Hepatitis B Virus (HBV)
• Hepatitis C Virus (HCV)
• Human T-lymphotropic Virus type 1 (HTLV-1)
• A participant who agrees to have their anonymized biological samples and cell lines stored in a biological sample collection for other research purposes (including genetic research)

Exclusion criteria

• Any active medical condition
• Any ongoingl treatment
• Subjects who cannot read and/or write
• Inability to ensure participant during the study period
• Participation in another clinical trial or administration of an off-label medication that could interfere with blood test results.
• Participation in another research protocol involving biological sampling that limits the number of mL to be collected.
• Failure to obtain informed consent
• Not enrolled in a social security program,
• Subject participating in another research study with an ongoing exclusion period
• Protected populations under the French Public Health Code (women who are giving birth, breastfeeding, or pregnant; subjects deprived of liberty by judicial or administrative decision; adults under legal protection (under any form of guardianship))