A thorough analysis finds tissue-specific stem cells make chemically and functionally different bone than embryonic ones
Many sorts of cells are able to form superficial bone-like nodules in culture, but how these nodules compare to native bone has been unclear. New work reveals that embryonic stem cells form a bone-like material quite different from that formed by adult-derived cells1. This finding has implications for osteogenic engineering, which could be used in the over two million bone-replacement procedures that take place every year.
Molly Stevens’s team at Imperial College London compared the nodules formed by neonatal osteoblasts from mice with those differentiated from both mouse mesenchymal stem cells (MSCs) and mouse embryonic stem (ES) cells. Although all of the nodules became calcified, this did not necessarily mean that they were forming similar bone-like material.
To look more deeply at the differences between the nodules, the researchers used a technique called Raman spectroscopy, which is based on the inelastic scattering of light by chemical bonds. The advantage of this, says Stevens, is that, “it gives information about the biomolecular components of the culture without a predisposition towards finding a particular result”. The experiments showed that prior to the onset of mineralization, osteoblasts and MSCs displayed many characteristics of native bone, including expression of key proteins in skeletal formation. Materials from ES cells, in contrast, expressed bone-related markers less strongly.
After mineralization, MSC- and osteoblast-derived nodules predominantly contained three interacting mineral types similar to those in native bone, whereas ES cell–derived nodules were dominated by less-complex mineral interactions. Defects in the mineralization process and, importantly, in the way that the mineral associated with the collagen meant that the ES cell–derived nodules lacked the all-important mechanical strength of both native bone and the osteoblast- and MSC-derived counterparts.
The paper is extremely compelling, but it doesn’t rule out the use of ES cells in osteogenic engineering, comments Doug Kniss of the Ohio State University in Columbus. Although the experiments were thorough, trying to make ES cells fast-forward through a set of developmental stages that the other cell types have already gone through could put them at a disadvantage. By tweaking and optimizing the culture conditions, researchers might be able to generate more authentic bone structures from ES cells.
Optimizing culture conditions could allow ES cells to make better bone, says Stevens. (And since ES cells are easier to maintain and expand in culture than other cell types, using them to make biomaterials has several practical advantages.) Even so, the resulting bone-like material will still need to be analyzed very thoroughly. As hard as it is to make a tissue outside the body, it can be harder still to compare engineered tissues to their natural counterparts. Bioengineered biomaterials that superficially resemble natural counterparts may not act the same way, says Stevens. For example, although it’s relatively straightforward to test whether cells are making the markers and expressing genes typical of lung tissue, she says, “it’s still extremely difficult to determine if these cells can mediate gas exchange as in vivo”.
And for the bone-forming cells, Stevens says, some starting materials may indeed be better than others at making the final bone-replacement product. “There is a fundamental difference between these cell types and the way they mineralize when exposed to identical conditions, and further study is required.” Understanding these differences will be essential for developing therapies.
1. Gentleman, E. et al. Comparative materials differences revealed in engineered bone as a function of cell specific differentiation. Nature Mater. advance online publication, doi:10.1038/NMAT2505 (26 July 2009).
Simone Alves is a freelance writer based in London.