Journal Article

Mapping the microcarrier design pathway to modernise clinical mesenchymal stromal cell expansion

Major, Gretel S., Wise, Steven G., Lim, Khoon S., Bilek, Marcela M.M., Doan, Vinh K., Longoni, Alessia, Rnjak-Kovacina, Jelena, Yeo, Giselle C.

2024

Overview

The current limitations of commercial microcarriers for mesenchymal stromal cell (MSC) expansion are driving the demand for novel tuneable microcarriers.Novel microcarriers are effective in improving MSC expansion under static and dynamic culture conditions without compromising their stemness and differentiation potential.Integrating microcarrier-based cultures within dynamic bioreactors provides an effective scalable approach for MSC expansion and harvest for downstream clinical translation.The development of good manufacturing practice (GMP)-grade systems, non-xenogenic culture media, and optimised bioreactors, which are compatible with novel microcarriers, is essential to improve cell yield and reproducibility. Microcarrier expansion systems show exciting potential to revolutionise mesenchymal stromal cell (MSC)-based clinical therapies by providing an opportunity for economical large-scale expansion of donor- and patient-derived cells. The poor reproducibility and efficiency of cell expansion on commercial polystyrene microcarriers have driven the development of novel microcarriers with tuneable physical, mechanical, and cell-instructive properties. These new microcarriers show innovation toward improving cell expansion outcomes, although their limited biological characterisation and compatibility with dynamic culture systems suggest the need to realign the microcarrier design pathway. Clear headway has been made toward developing infrastructure necessary for scaling up these technologies; however, key challenges remain in characterising the wholistic effects of microcarrier properties on the biological fate and function of expanded MSCs. Microcarrier expansion systems show exciting potential to revolutionise mesenchymal stromal cell (MSC)-based clinical therapies by providing an opportunity for economical large-scale expansion of donor- and patient-derived cells. The poor reproducibility and efficiency of cell expansion on commercial polystyrene microcarriers have driven the development of novel microcarriers with tuneable physical, mechanical, and cell-instructive properties. These new microcarriers show innovation toward improving cell expansion outcomes, although their limited biological characterisation and compatibility with dynamic culture systems suggest the need to realign the microcarrier design pathway. Clear headway has been made toward developing infrastructure necessary for scaling up these technologies; however, key challenges remain in characterising the wholistic effects of microcarrier properties on the biological fate and function of expanded MSCs.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Biological properties / biomaterials / bioreactors / biotechnology / cell attachment / Cell culture / Cell Culture Techniques - instrumentation / Cell Culture Techniques - methods / Cell Proliferation / Cellulose / differentiation / dynamic culture / Efficiency / Enzymes / Good Manufacturing Practice / Humans / infrastructure / Internal Medicine / Manufacturing / Mesenchymal stem cells / Mesenchymal Stem Cells - cytology / mesenchymal stromal cells / Modernization / Polystyrene / Polystyrene resins / polystyrenes / Regenerative medicine / Reproducibility / Stem cells / surface modifications / Wound healing