Boning up on tissue engineering.

The past two years have been an exciting time for the field of tissue engineering. There have been remarkable advances in eliciting the full developmental potential of stem cells from a number of mammalian tissues. In addition, the generation of human embryonic stem cell lines heralds a future in which a variety of tissues can be generated in culture to replace or to augment failing organ systems in vivo.One such platform on which this technology can be and is being applied is bone development. Congenital bone defects and resections necessitated by osteosarcoma are classically treated by reconstructive surgery using bone autografts or banked tissue. Unfortunately, bone regeneration in large lesions is often limited, resulting in poor union with pre-existing bone and scarring. To address this problem, clinicians have attempted to promote the proliferation and differentiation of bone cells in vivo by implanting natural or synthetic scaffolds that provide the three-dimensional architecture necessary for osteogenesis. Unfortunately, the success of these implants has been limited and efforts to study this problem in the research laboratory have been hampered by a lack of suitable culture systems that promote the ex vivo formation of human bone.The September issue of Nature Biotechnology contains two reports that represent major advances towards addressing these problems. Importantly, both papers underscore the critical need for osteogenic cells to be placed close together in a three-dimensional architecture that is reminiscent of their organization in the developing embryo. First, Kale et al.xThree-dimensional cellular development is essential for ex vivo formation of human bone. Kale, S. et al. Nat. Biotechnol. 2000; 18: 954–958Crossref | PubMed | Scopus (175)See all ReferencesKale et al. report that the stimulation of human bone cells with transforming growth factor β1 (TGF β1) in serum-free cultures causes them to condense into multicellular spheroids. This condensation appears, in vitro, to be the event that triggers the up-regulation of several bone-related proteins and the deposition of crystalline microspicules that are reminiscent of organized bone.Petite et al.xTissue-engineered bone regeneration. Petite, H. et al. Nat. Biotechnol. 2000; 18: 959–963Crossref | PubMed | Scopus (905)See all ReferencesPetite et al. have shown the need for close cell positioning in vivo by seeding a natural ceramic scaffold from Porites coral with regeneration-competent mesenchymal stem cells (MSC) that had been isolated from bone marrow and expanded for several weeks in vitro. The highly porous coral templates facilitated vascularization and successfully guided bone morphogenesis and regeneration when surgically implanted into injured bones in sheep. Tissue-engineered bone corrected clinically relevant defects in three of seven animals, and the coral scaffold was resorbed after four months.These advances represent an important milestone in the journey towards a full understanding of bone-tissue engineering. Kale's system of TGF-β1-mediated bone formation provides an invaluable tool for analysing the physiological and molecular regulation of osteogenesis ex vivo. Petite's system offers a clinically relevant model for evaluating the role of primitive MSCs and any functional effects of inducing their differentiation or otherwise manipulating such bone precursors in vitro. It would be interesting to combine the strategies in these two papers and to test whether stimulating MSCs with TGF-β1 or other cytokines before seeding coral implants would enhance their osteogenic potential. Tissue engineering is clearly coming of age and the time is here for transplantation biologists from diverse fields to ‘bone up’ on emerging technologies.