Off-the-Shelf Cord-Blood Mesenchymal Stromal Cells: Production, Quality Control, and Clinical Use

Area of Science:

• Cellular and Molecular Medicine
• Immunology
• Regenerative Medicine

Background:

• Mesenchymal stromal cells (MSCs) are recognized for their role in transplantation, offering immune tolerance and reducing reliance on immunosuppressive drugs.
• Cord blood (CB)-derived MSCs are particularly valuable due to their immunological naivety and potent anti-inflammatory and anti-apoptotic properties.

Purpose of the Study:

• To establish an inventory of CB-derived MSCs suitable for large-scale advanced therapy medicinal product (ATMP)-based clinical trials.
• To detail the manufacturing process and clinical applications of GMP-certified MSCs.

Main Methods:

• MSCs were isolated using plastic adherence in a Good Manufacturing Practice (GMP)-compliant system.
• A master cell bank and working cell bank were established, producing certified MSC(CB) batches for clinical use.
• The regulatory framework for ATMPs, emphasizing quality control and safety, was considered.

Main Results:

• A well-defined MSC manufacturing process was demonstrated as feasible.
• 263 GMP-certified MSC(CB) preparations were administered to 40 subjects with Graft-vs.-Host Disease, nephrotic syndrome, or bronco-pulmonary dysplasia.
• No infusion-related adverse events or grade toxicity were observed; encouraging preliminary outcomes and clinical responses were reported.

Conclusions:

• Ten years of experience with MSC(CB) provide valuable insights into their use for immune-mediated diseases.
• GMP-compliant manufacturing enables the clinical application of MSCs as innovative cell-based therapies.