Stem Cells for Osteochondral Regeneration

Abstract

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.

TGF-β1 promoted chondrocyte proliferation by regulating Sp1 through MSC-exosomes derived miR-135b

“…Recently, MSC-based therapy has been considered as a novel therapy for the treatment of tissue repair. MSC transplantation could protect cartilage from degeneration in OA [18][19][20]. Besides that, growing evidence suggests that MSCs mediate tissue repair through its secretion [2,21].…”

Osteochondral Tissue Engineering: The Potential of Electrospinning and Additive Manufacturing

“…Several potential cell sources ( Table 2 and Figure 4 ) have already been described for use in bone [ 191 ] and cartilage [ 192 ] tissue regeneration. These could be applied in OCTE strategies, as schematically illustrated in Figure 5 ; however, the selection of a suitable cell source that satisfies the needs of osseous and chondral tissues, as well as of the cartilage-to-bone interface, is still an ongoing issue [ 38 , 193 , 194 ]. Some strategies focus on using a single cell source with chondrogenic and osteogenic differentiation capacity, while others use multiple cell sources (either primary and/or stem cell-derived) to mimic the bone and cartilage components of the OC unit [ 38 , 193 ].…”

“…As a means to overcome the hurdles associated with primary cells, considerable attention has been given to the use of alternative cell sources, such as stem cells. Among these, human embryonic stem cells (hESCs), adult MSC and, more recently, induced pluripotent stem cells (iPSCs) can be highlighted mostly due to their wide availability, pluri- or multipotency, in vitro proliferation capacity and the ability to differentiate into both osteogenic and chondrogenic cell lineages [ 193 ]. To date, both in vitro and in vivo studies have shown the chondrogenic [ 196 , 197 ] and osteogenic [ 198 , 199 ] differentiation ability of hESCs, and expansion protocols have been developed so that hESC-derived cells can be applied in OCTE strategies.…”

LncRNA H19 Regulates BMP2-Induced Hypertrophic Differentiation of Mesenchymal Stem Cells by Promoting Runx2 Phosphorylation

“…Stem-cell-based and gene-enhanced tissue engineered cartilage is promising in the treatment of cartilaginous pathologies, especially traumatic cartilage defects (Bishop et al, 2017;Canadas et al, 2018;Wang et al, 2019). Mesenchymal stem cells (MSCs) hold the potential for osteogenic, chondrogenic, adipogenic differentiation, etc., owing to the fact that MSCs are easy to isolate, stable in expressing exogenous genes, abundant in source, and were identified as ideal seed cells for regenerative medicine (Canadas et al, 2018;Kim et al, 2019;Mamidi et al, 2016;Wang et al, 2019). Therefore, it is essential to guide MSC chondrogenic differentiation for the construction of tissue engineering cartilage.…”