Stem cells for osteochondral regeneration

Stem cell research plays a central role in the future of medicine, which is mainly dependent on the advances on regenerative medicine (RM), specifically in the disciplines of tissue engineering (TE) and cellular therapeutics. All RM strategies depend upon the harnessing, stimulation, or guidance of endogenous developmental or repair processes in which cells have an important role. Among the most clinically challenging disorders, cartilage degeneration, which also affects subchondral bone becoming an osteochondral (OC) defect, is one of the most demanding. Although primary cells have been clinically applied, stem cells are currently seen as the promising tool of RM-related research because of its availability, in vitro proliferation ability, pluri- or multipotency, and immunosuppressive features. Being the OC unit, a transition from the bone to cartilage, mesenchymal stem cells (MSCs) are the main focus for OC regeneration. Promising alternatives, which can also be obtained from the patient or at banks and have great differentiation potential toward a wide range of specific cell types, have been reported. Still, ethical concerns and tumorigenic risk are currently under discussion and assessment. In this book chapter, we revise the existing stem cell-based approaches for engineering bone and cartilage, focusing on cell therapy and TE. Furthermore, 3D OC composites based on cell co-cultures are described. Finally, future directions and challenges still to be faced are critically discussed.H2020-MSCA-RISE program, as this work is part of developments carried out in BAMOS project, funded from the European Union's Horizon 2020 research and innovation program under grant agreement Nº 734156. Thanks are also due to the Portuguese Foundation for Science and Technology (FCT) for the distinction attributed to J. M. Oliveira (IF/00423/2012 and IF/01285/2015) and to Rogério Pirraco (IF/00347/2015) under the Investigator FCT program. The authors also thank FCT for the Ph.D. scholarship provided to R. F. Canadas (SFRH/BD/92565/2013)info:eu-repo/semantics/publishedVersio