Implementation of mDoE-methods to a microcarrier-based expansion processes for mesenchymal stem cells

Area of Science:

• Biotechnology
• Cell Biology
• Process Engineering

Background:

• Advanced therapy medicinal products (ATMPs) require efficient cell manufacturing.
• Cell expansion processes face challenges with primary cells and microcarrier systems.
• Model-assisted Design of Experiments (mDoE) accelerates process development.

Purpose of the Study:

• To develop an optimized cell expansion process for human immortalized mesenchymal stem cells (hMSC-TERT).
• To maximize cell yield using mDoE with limited prior knowledge.
• To implement microcarrier-based expansion in shake flasks.

Main Methods:

• Screening of microcarriers for hMSC-TERT expansion in shake flasks.
• Generation of initial experimental data for mathematical model development.
• Application of mDoE to define and evaluate the experimental design space.

Main Results:

• Successful implementation of a microcarrier-based cell expansion process.
• Significant increase in cell yield (up to 6.2-fold) compared to literature values.
• Demonstration of hMSC-TERT differentiation potential.

Conclusions:

• mDoE is an effective strategy for optimizing ATMP cell expansion processes.
• The developed process enhances cell yield for hMSC-TERT.
• This methodology facilitates early-stage process development with minimal prior knowledge.