Clinical grade expansion of MSCs

Area of Science:

• Cellular therapy
• Biotechnology
• Good Manufacturing Practice (GMP)

Background:

• Advanced therapy medicinal products (ATMP) require strict Good Manufacturing Practice (GMP) compliance for clinical use.
• Mesenchymal stromal cells (MSCs) are a key cell type for various cellular therapies.
• Current GMP production faces challenges in scaling cell expansion for human use.

Purpose of the Study:

• To report manufacturing experience with 103 clinical-grade in vitro expansions of mesenchymal stromal cells (MSCs).
• To evaluate the feasibility and reproducibility of using animal- and serum-free medium supplemented with human platelet lysate for MSC expansion.
• To demonstrate the capacity of the Cell Factory to produce sufficient MSCs for clinical trials.

Main Methods:

• Conducted 103 consecutive clinical-grade in vitro expansions of bone marrow- and umbilical cord-derived MSCs.
• Utilized a standardized animal- and serum-free medium with human platelet lysate for all expansions.
• Described the specific methods and reagents employed in the Cell Factory.

Main Results:

• Successfully produced a sufficient number of MSCs to treat 57 patients across 7 phase I/II clinical protocols.
• Demonstrated the feasibility and reproducibility of the described MSC manufacturing process.
• This represents the largest published experience using human platelet lysate as a clinical-grade reagent for MSC expansion.

Conclusions:

• The use of animal- and serum-free medium with human platelet lysate is a viable and reproducible method for clinical-grade MSC production.
• This manufacturing strategy supports the expansion of MSCs for advanced cellular therapies under GMP conditions.
• The Cell Factory successfully scaled MSC production to meet clinical trial demands.