Model with living bone cells to study osteoporosis
Stefan Remmers defended his thesis at the Department of Biomedical Engineering on March 14th.
Osteoporosis is a disease in which bones slowly become more fragile, increasing the risk of bone fractures. The progress of osteoporosis can be slowed down, but cannot be cured yet. For his PhD research, Stefan Remmers of the Orthopedic Biomechanics group, developed a model with living bone cells in which diseases such as osteoporosis, and the effect of various treatments on it, can be studied at a patient-specific level.
While bones look like solid pieces of hard material in which not much changes, a lot is actually going on inside. Two types of cells are constantly removing old and damaged tissue and replacing it with new tissue, especially under stress. Astronauts in space, for example, lose some of their bone mass, while people who exercise a lot gain stronger bones.
In a healthy individual, bone resorption and formation are in equilibrium, maintaining the necessary bone strength and structure. In diseases such as osteoporosis this equilibrium is disturbed, leading to pathological changes in bone mass that affect the bone’s mechanical functionality.
Measuring simultanously
To study this process, the bone-forming osteoblasts and the bone-removing osteoclasts, can be isolated from patients and used in the lab in cell culture experiments. These cell culture experiments are typically done with plastic plates containing high numbers of flat-bottomed wells, because that is the most practical and economic way to have large numbers of datapoints. Since bone is a 3D tissue where its growth depends its 3D environment, using these flat wells may not be very appropriate.
Next to that, in order to predict how a patient would respond to a drug for osteoporosis, it is important to study not only bone build-up but also bone breakdown to see the overall effect of the drug on bone tissue. Finally, there are many analytical techniques where cells must be sacrificed to get to the results. Therefore, to see the effect of a drug at different times over a longer period of time, different cell cultures must be used. Ideally, we would like to look at the same cell culture over and over again during that period, and study the actual changes over time.
To overcome these challenges, Stefan worked on a model in which bone remodeling and bone degradation can be measured simultaneously over time.
Model with living bone cells
Remmers developed a homemade 3D piece of mini bone with both the osteoblasts as well as the osteoclasts. With this model, he could study changes in bone formation and bone degradation over time. More importantly, he showed that by adding certain cell signals, this bone-forming and bone-degrading behaviour could even be steered.
Remmers concludes: “Imagine if we could take cells from an osteoporosis patient and put them into the model. Instead of trying new drugs over and over again on the patient himself, we can then use a wide range of drugs to test on these mini bones. This way we can test a multitude of drugs or drug combinations at once and see exactly which drugs work best for that particular patient. With any luck, we can even find a drug combination that can completely stop the progression of osteoporosis.”
Title of PhD thesis: The amazing osteoclast: Towards an in vitro 3D co-culture model of bone Supervisors: Keita Ito and Sandra Hofmann.