The potential of human fetal mesenchymal stem cells for off-the-shelf bone tissue engineering application

Mesenchymal stem cells (MSCs) have become one of the most promising cell sources for bone tissue engineering (BTE) applications. In this review, we first highlight recent progress in the understanding of MSC biology, their in vivo niche, multi-faceted contribution to fracture healing and bone re-modelling, and their role in BTE. A literature review from clinicaltrials.gov and Pubmed on clinical usage of MSC for both orthopedic and non-orthopedic indications suggests that translational use of MSC for BTE indications is likely to bear fruit in the ensuing decade. Last, we disscuss the profound influence of ontological and antomical origins of MSC on their proliferation and osteogenesis and demonstrated human fetal MSC (hfMSC) as a superior cellular candidate for off-the-shelf BTE applications. This relates to their superior proliferation capacity, more robust osteogenic potential and lower immunogenecity, as compared to MSC from perinatal and postnatal sources. Furthermore, we discuss our experience in developing a hfMSC based BTE strategy with the integrated use of bioreactor-based dynamic priming within macroporous scaffolds, now ready for evaluation in clinical trials. In conclusion, hfMSC is likely the most promising cell source for allogeneic based BTE application, with proven advantages compared to other MSC based ones.