Since the 1980s, it was realized that mesenchymal stem cells (MSC’s) can be utilized to engineer mesenchymal tissues, such as bone and cartilage. Bone marrow has been claimed to be the most abundant source of MSC’s, which have a high proliferative ability and great capacity for differentiation. The challenge is to combine mesenchymal stem cells with a scaffold, to allow paracrine and host derived factors to produce bone matrix after implantation. Indeed, the proof of concept was not only proven in rodents, but also in larger animals. For example, bone formation was induced both in segmental femur defects (dog), in reconstructed skull and mandibular defects (sheep) as in iliac wing defects (goat).

Surprisingly, despite the promising future as predicted, in humans only a few case reports of successful reconstructions have been published. In patients with various intra-oral defects, who underwent reconstruction with cells cultured on a coralline hydroxyapatite (HA) scaffold, also we were able to confirm that bone formation by implanted cells is feasible.

To achieve clinical success, cell survival is the most important issue in cell-based bone tissue engineering. Such cell survival can be consolidated by various means such as: (1) co-culturing endothelial cells, (2) bypassing the deleterious effect of the hematoma and lack of early vascularisation by a two step implantation procedure; first the scaffold and approximately one week later injection of the MSCs. Another approach (3) would be to ectopically implant the tissue engineering construct in a well vascularised site in the body, i.e. muscle, to allow bone formation, followed by transplantation to the defect site. However, on the spot repair, which is currently obtained by autologous bone grafting is still the optimal approach.

Indisputable is that MSCs are crucial for the healing of bone defects. Besides the above mentioned cell-based techniques, another approach would be to recruit MSCs to the implantation site by growth factors or “smart” scaffolds. The use of these so-called osteoinductive scaffolds or one of the other mentioned alternative approaches could well revolutionise the future of regenerative medicine.

Hydroxyapatite particles stained with methylene blue immediate after seeding of patient’s own mesenchymal stem cells (left, showing cell distribution), and histology after 4 months of implantation in the upper left tooth region (right, showing bone formation induced by the implanted cells (arrows).

Key reference

Meijer GJ, de Bruijn JD, Koole R, van Blitterswijk CA. Cell-Based Bone Tissue Engineering.
PLoS Med. 2007;4(2):e9