Scientists [Gentleman et al., DOI: 10.1038/NMAT2505 ] have successfully highlighted the importance of cell source in regenerative medicine. Stevens and her team formed mineralized nodules in vitro from mouse ESC, neonatal calvarial osteoblasts (OB) and adult bone-marrow-derived mesenchymal stem cells (MSC) and compared them with one another and native bone using a combination of materials and biological characterization methods.

Disease and injury so severe that the body cannot heal naturally necessitate clinical intervention to restore a level of tissue function. One aim of regenerative medicine is to meet this need with laboratory-grown constructs that can be surgically implanted, as they may avoid many problems associated with allogenic and autogenic grafts such as limited availability, immune compatibility, and disease transmission.

Bone is a prime target for regenerative medicine therapies with over two million replacement procedures carried out annually worldwide. Bone is also an ideal tissue for investigating cell sources for regenerative medicine, as cells derived from bone, adult stem cells have all been reported to form mineralized, bone-like nodules in vitro. Despite this, a detailed comparative understanding of the biological activities, architecture, mechanical properties and biochemical/material composition of these nodules is still elusive. In the body, bone develops through a tightly regulated process leading to a hierarchically ordered, three-dimensional structure. It is unclear how similar the mineralized material formed from cells cultured in vitro is to native bone.

Analysis was carried out on live cell cultures using micro-Raman spectroscopy, a non- destructive technique based on the inelastic scattering of light by chemical bonds, which can be used to determine the biomolecular composition of cells or tissues by the relative intensities of characteristic molecular vibrations.

Such simple analyses, however, ignore the complexity of interactions between multiple mineral environments present in native bone. Therefore, Stevens et al., also applied the multivariate technique, factor analysis, to Raman spectra of day-28 mineralized nodules. Factor analysis can be used to interpret the results of principal-component analysis, a multivariate technique used to analyse large, complex data sets. Principal-component analysis generates `principal components’, which contain spectral features corresponding to the molecular species responsible for statistical variation between spectra. When applied to spectra of mineralized nodules, the principal components can be ‘rotated’ (linearly combined) to give ‘factors’ that describe the mineral and matrix environments in a sample.

Results reveal clear differences in the bone-like material formed. They also provide insight into the biological mechanisms that drive these processes, and highlight the importance of cell source in regenerative medicine.