On June 19th, Michelle Vis successfully defended her thesis, entitled:” Microenvironmental advancement and miniaturization of human in vitro bone models” models’ at the Department of Biomedical Engineering of the Eindhoven University of Technology. Her research was performed under the supervision of Sandra Hofmann and Keita Ito.
Human in vitro models are being developed in order to reduce or replace traditional animal models, which often fall short in replicating diseases or their treatment. The PhD thesis of Michelle Vis focused first on downscaling an existing 3D in vitro bone remodeling model onto the size of a human trabeculae which fits into a microfluidic chip. Further, the microenvironment of the models needed to be improvee to represent a balance between osteoblasts and osteoclasts. This is essential to represent bone homeostasis, where bone formation and resorption are equal. In most bone diseases, this balance is disturbed. Her research aims to revolutionize bone research and pave the way for understanding, preventing and treating bone disease in a human-specific context.
More specifically, the focus of her study were cocultures between bone forming osteoblasts and bone resorbing osteoclasts are grown simultaneously from progenitor cells. While this allows to study the communication and interaction between these cells, it also poses new challenges. One potent way in which cells communicate with each other is through the secretion of soluble factors as signaling molecules. In most cell cultures, the refreshing of the cell culture medium several times a week means that these factors are ‘thrown away’ and replaced with new, signaling-molecule-free fresh medium enriched with nutrients.
During her thesis, Michelle has developed a dialysis-based method to ‘recycle’ and keep the signaling molecules. She has shown that this approach provides a more efficient microenvironment compared to conventional culture methods by preserving the communication between osteoblasts and osteoclasts.
Next, she explored how microfluidic chips can be used to downscale an existing in vitro bone remodeling model to fit into a microfluidic device. She miniaturized a coculture in which first human-derived progenitor cells were differentiated into osteoblasts and self-assembled into three-dimensional bone-like tissues, resembling bone trabeculae. By adding human monocytes as osteoclast progenitor cells to these tissues, she was able to enable a long-term coculture of both osteoblast- and osteoclast-like cells on a chip.
This research provides validated strategies for improving the microenvironment and miniaturization of in vitro bone remodeling models. It also demonstrates the first fully human osteoblast-osteoclast coculture on a chip. This research strives to improve in vitro models and has the ultimate goal of replacing, reducing and refining the use of animal models.