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.

11th Yahya Cohen Memorial Lecture: An in vivo comparative study of the ability of derived mesenchymal stem cells in the treatment of partial growth arrest

Few in vivo studies had previously been attempted in reaffirming the in vitro data in current literature. This study evaluated the ability of mesenchymal stem cells (MSCs) isolated from bone marrow, periosteum and fat to treat partial growth arrest in immature New Zealand white (NZW) rabbits. A physeal arrest model in an immature rabbit was created. The bony bridge was excised 3 weeks later, and MSCs from various sources were transferred into the physeal defect of different rabbits. Group I consisted of bone marrow-derived MSCs, Group II: periosteumderived MSCs, Group III: fat-derived MSCs. Contra-lateral tibiae, without undergoing operation, served as self-control. The animals were subsequently sacrificed, with radiological and histological analyses performed. All MSCs demonstrated chondrogenic and osteogenic differentiation potentials in vitro. In correction of varus angulation groups I and II exhibited superior results when compared to group III (P <0.05). The length discrepancies between operated and normal tibiae in groups I, II and III were significantly corrected when compared to the control group (P <0.01). In conclusion, bone marrow and periosteum derived stem cells provided better correction of physeal arrest in rabbits. The source of MSCs itself could influence the success in the treatment of growth arrest.