3D printed bone tissue engineered to study the spread of cancer
Worldwide Cancer Research funded researchers in Brisbane, Australia, have found a way to grow human bone ‘organs’ in mice to improve the study of cancer spread (metastasis) to the bone. The study, published in the journal Nature Protocols, could help researchers to better understand the biology that leads to cancer cells forming tumours in bone. Cancer that has spread away from the original tumour is a hallmark of more aggressive disease that is much harder to treat. Research that tells us more about how this occurs will ultimately help discover ways to stop it from happening.
“Over the last decade, major research efforts have focused on developing alternative ways to study cancer within the bone tissue, but the current lab models do not reflect the true nature of human bone” said lead researcher Distinguished Professor Dietmar W. Hutmacher. “We used a clinically established bone engineering platform developed by our lab to build a bone environment from human cells that we were able to implant into mice to more accurately capture what is happening in human bone tissue. This model could allow for more unfailing evaluation of new anticancer drugs and improve the efficacy of therapeutic strategies against the spread of cancer to the bone.”
A better way to study bone
The most insightful method currently used to study bone metastasis involves what is known as a ‘xenograft’ mouse model, where human cancer cells are transplanted into mice. These xenograft models can reveal important aspects of biology, yet are limited when trying to study exactly how tumours interact with other tissues or cell types in the surrounding area – an important factor involved in the development of secondary cancers. Essentially, this model of metastasis is not fully representative of what is happening in a person.
The Hutmacher lab has now developed a mouse model that aims to “make mice bone as human as possible”. Using their expertise in bioengineering, they were able to develop what they call a human tissue-engineered bone construct that, when implanted into mice, forms a tissue that more closely represents true bone physiology.
3D printing bone
The first step in developing a humanized bone organ is to create a scaffold on which human bone can be grown. Using a 3D printing technique, called melt electrospinning writing, the researchers force a medical grade polymer (large molecule) through an electrical field, to produce fibrous meshes on which human cells can grow. The scaffold is built on a rotating steel spindle to create a tube that captures a bone-like shape, containing an outer wall, as well as an inner cavity where the bone marrow and internal bone structures would form.
Then comes the molecular magic. The scaffolds are seeded and cultivated with human osteoblasts – cells that are capable of forming bone – and treated with chemicals that encourage them to grow and produce a mineralised extracellular matrix. The result is the formation of microscopic bone-like structures inside the scaffold. For this to represent a bone ‘organ’ there also needs to be a bone marrow compartment and a connection to a blood supply. To achieve this, the researchers implanted the tissue-engineered construct into mice and exposed them to human bone marrow cells which support an active bone marrow compartment. Once implanted, the human bone cells in the scaffold send out chemical signals that recruit mouse cells to the scaffold that are capable of forming new blood vessels.
Using the model to study cancer
This novel approach offers a number of opportunities to study the spread of cancer to the bone. The improved level of humanization means that the model allows scientists to look in greater detail at what causes cancer cells to set up home in the bone. There is also potential to develop the model further, to study the development of primary bone cancers, such as sarcomas, and even cancers that originate in the bone marrow, such as myeloma.
One exciting prospect for this model is to study patient-specific responses to treatments. Professor Hutmacher explained: “Cancer cells and healthy cells from the same affected individual can be harvested and prepared in order to be engrafted and investigated in one humanized in vivo platform. Such a model could be used as a diagnostic tool, as well as enabling patient-matched molecular targets to be identified, directed at, and translated into individual clinical applications.”
The original research article is available online here: http://www.nature.com/nprot/journal/v12/n4/abs/nprot.2017.002.html?foxtrotcallback=true
Image credit: UCL Engineering/Flickr