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(1) In vitro, bone marrow-derived stromal cells (BMSCs) demonstrate inter-donor phenotypic variability, which presents challenges for the development of regenerative therapies. Here, we investigated whether the frequency of putative BMSC sub-populations within the freshly isolated mononuclear cell fraction of bone marrow is phenotypically predictive for the in vitro derived stromal cell culture. (2) Vertebral body, iliac crest, and femoral head bone marrow were acquired from 33 patients (10 female and 23 male, age range 14-91). BMSC sub-populations were identified within freshly isolated mononuclear cell fractions based on cell-surface marker profiles. Stromal cells were expanded in monolayer on tissue culture plastic. Phenotypic assessment of in vitro derived cell cultures was performed by examining growth kinetics, chondrogenic, osteogenic, and adipogenic differentiation. (3) Gender, donor age, and anatomical site were neither predictive for the total yield nor the population doubling time of in vitro derived BMSC cultures. The abundance of freshly isolated progenitor sub-populations (CD45-CD34-CD73+, CD45-CD34-CD146+, NG2+CD146+) was not phenotypically predictive of derived stromal cell cultures in terms of growth kinetics nor plasticity. BMSCs derived from iliac crest and vertebral body bone marrow were more responsive to chondrogenic induction, forming superior cartilaginous tissue in vitro, compared to those isolated from femoral head. (4) The identification of discrete progenitor populations in bone marrow by current cell-surface marker profiling is not predictive for subsequently derived in vitro BMSC cultures. Overall, the iliac crest and the vertebral body offer a more reliable tissue source of stromal progenitor cells for cartilage repair strategies compared to femoral head.

This position paper summarises a vision of how cell-based therapies can be applied clinically to regenerate bone, as well as the steps needed to narrow the gap between that vision and clinical reality. It is a result of the presentations and discussion of the "Cell Therapy for Bone Repair" breakout session at the AO Foundation Symposium "Where Science Meets Clinics" in Davos, Switzerland from September 5-7, 2013. Participants included leaders from science, medicine, and industry from around the world. The session included clinical and scientific presentations, as well as an extended discussion among participants. Bone tissue has an innate regenerative capacity that in most cases allows functional healing at damage sites. However, there are a number of serious conditions in which bone does not fully heal and the result is significant morbidity. The clinical need for new therapies is clear, and the breakout session participants were enthusiastic about the potential impact on cell-based therapies for bone repair in the clinic. However, they also recognised the significant challenges that face the development of commercially viable cell therapy products. This paper outlines a vision in which patient selection is based on expected therapeutic outcome to create a consistently successful, cost-effective, cell-based therapy for bone repair. The need for a more complete understanding of bone repair, a better infrastructure for preclinical studies, and the need for collaboration among stakeholders is discussed.