It is increasingly clear that to understand the complex processes that regulate the human body, it is no longer sufficient to rely entirely on a single approach. There has been a drive over the past decade to enhance co-operation between different academic disciplines such as biology, medicine, engineering, mathematics and informatics to improve understanding of disease and thereby develop novel therapeutic approaches.
An example of the promising results such an integrated approach can yield is the paper published by shih et al. in Proceedings of the National Academy of Sciences which elucidates an important osteogenic mechanism. This study used engineered calcium phosphate (CaP)-rich synthetic matrices to investigate the in vitro differentiation of human mesenchymal stem cells into osteoblasts, the main cell type involved in bone growth and homeostasis. The researchers found that dissociation of calcium and phosphate ions occurred freely from the matrix, but the phospate ions were key to stem cell differentiation. Briefly, the SLC20a1 transporter enabled uptake of extracellular phosphate. In turn, phosphate increased ATP synthesis via mitochondrial metabolism prior to ATP being exported from the cell. This extracellular ATP was degraded to adenosine via a number of enzymes. Adenosine, through binding its cell-surface receptor in autocrine/paracrine fashion was able to activate osteogenic signalling pathways.
As well as highlighting the importance of inter-disciplinary research this study has key implications for a variety of diseases where defects in bone homeostasis occur, including osteoporosis, osteoarthritis and osteomalacia. By surgically implanting such bioengineered matrices it may be possible to induce a switch from catabolism to anabolism and discover new receptors or enzymes involved in osteogenesis that are amenable to pharmaceutical intervention. Further studies investigating the in-vivo stability of such matrices must be carried out as well as any issues that may arise due to interaction of these materials with host immune cells. Nevertheless, the age of revolution in biosystems engineering draws ever closer.
References
shih et al. Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signalling Proceedings of the National Academy of Sciences January 2014 (vol. 111, issue 3)
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