Biomimetic matrices resemble living structures even though they are made from synthetic materials. Researchers in the laboratory of Shyni Varghese at the UC San Diego Jacobs School of Engineering have used calcium phosphate to direct mesenchymal stem cells to form bone. In doing so, Varghese and his colleagues have identified a surprising pathway from biomaterials to bone.
Varghese and his colleagues think that their work may point out new targets for treating bone defects, such as major fractures, and bone metabolic disorders such as osteoporosis.
The first goal of this research was to use materials to build something that looked like bone. This way, stem cells harvested from bone marrow (the squishy stuff inside our bones) could sense the presence of bone and differentiate into osteoblasts, the cells in our bodies that build bone.
“We knew for years that calcium phosphate-based materials promote osteogenic differentiation of stem cells, but none of use knew why.” said Varghese. “As engineers, we want to build something that is reproducible and consistent, so we need to know how building factors contribute to this end.”
Varghese and co-workers discovered that phosphate ions dissolved from calcium phosphate-based materials and these stray phosphate ions are taken up by the stem cells and used for the production of adenosine triphosphate or ATP. ATP is the energy currency of the cell, and it is the way cells store energy in a form that is readily usable for powering other reactions.
In stem cells, the generation of ATP eventually increases the intracellular concentration of the ATP breakdown product adenosine, and adenosine signals to stem cells to differentiate into osteoblasts and make bone.
Varghese said that she was surprised that “the biomaterials were connected to metabolic pathways. And we didn’t know how these metabolic pathways could influence stem cells,” and their commitment to bone formation.
These results also explain another clinical observation. Plastic surgeons have been using fat-based stem cells for eyelid lifts, breast augmentation, and other types of reconstructive surgeries. In once case, a plastic surgeon injected a dermal filler that contained calcium hydroxyapatite with the fat-based stem cells into a woman’s eyelid to provide an eye lift. However, the stem cells formed bone, and the poor lady’s lid painfully clicked every time she blinked and she had to have surgery to remove the ectopic bone. These results from Varghese’s laboratory explains why these fat-based stem cells formed bone in this case, and great care should be taken to never use such fillers in fat-based transplantation procedures.