Strategies for MSC expansion and MSC-based microtissue for bone regeneration

Mesenchymal stem cells (MSCs) have gained increasing attention as a potential approach for the treatment of bone injuries due to their multi-lineage differentiation potential and also their ability to recognize and home to damaged tissue sites, secreting bioactive factors that can modulate the immune system and enhance tissue repair. However, a wide gap between the number of MSCs obtainable from the donor site and the number required for implantation, as well as the lack of understanding of MSC functions under different in vitro and in vivo microenvironment, hinders the progression of MSCs toward clinical settings. The clinical translation of MSCs pre-requisites a scalable expansion process for the biomanufacturing of therapeutically qualified cells. This review briefly introduces the features of implanted MSCs to determine the best strategies to optimize their regenerative capacity, as well as the current MSC implantation for bone diseases. Current achievements for expansion of MSCs using various culturing methods, bioreactor technologies, biomaterial platforms, as well as microtissue-based expansion strategies are also discussed, providing new insights into future large-scale MSC expansion and clinical applications.