Researchers have developed a method to make miniature models of human bones in the laboratory. This enables diseases such as blood cancer and bone metastasis to be studied much more easily. These mini-bones may one day be used to test whether specific drugs work on a specific individual with cancer.
When researchers study living biology in the laboratory, they prefer to do this in systems that are as close to reality as possible.
This also applies to the biology of human bones and understanding why people develop blood cancer or bone metastasis. The problem in this context is that this has only been possible with bones from mice, and these are not identical to human bones.
Researchers have now solved this problem by developing a method to make human mini-bones in the laboratory. They are made from human stem cells and are therefore much better suited to study many aspects of human bone health.
This also enables drugs to be developed much more easily to combat diseases that affect the bones.
“We still need to understand much of what happens in human bones. One reason is that we have not had access to good systems for studying their biology. For example, up to 90% of all drug candidates fail because they are only effective in animal models but not in people. With the development of our human bone model, we can much better study human diseases and the effectiveness of drugs to treat them,” explains a researcher involved in the study, Paul Bourgine, Associate Senior Lecturer, Lund University, Sweden.
The research has been published in Science Translational Medicine.
Human cartilage implanted into the backs of mice
The researchers developed a method to use a cell line from humans to form bones in the laboratory.
The method uses mesenchymal stem cells, which can become cartilage cells and then become other cells such as bone cells and fat cells.
The researchers engineer the stem cells with various biochemical factors that cause them to become cartilage cells, which they seed on collagen scaffolding material in the laboratory to give the cartilage cells a three-dimensional structure.
Once the cartilage cells have formed the right structure, which takes about 3 weeks, the researchers implant the piece of cartilage under the skin in the backs of mice. The piece of cartilage develops and forms natural bone and bone marrow as in a real human bone.
“Our mini-bones develop like the bones of a teenager. The cartilage becomes calcified and populated with bone marrow cells. The biology of the mice helps the human cartilage cells to mature into human bones, and we inject haematopoietic stem cells into the mini-bone to reconstitute the human bone marrow,” says Paul Bourgine.
Advancing researchers’ knowledge on the biology behind cancer
The mini-bones enable researchers to study bone biology more easily and learn about all the mechanisms and signalling pathways needed to make healthy bones function properly.
Researchers can also take diseased cells from, for example, someone with bone marrow cancer and grow them in the mini-bones, enabling them to learn more about the specific biology of disease of the individual person.
“Many types of cancer cannot be studied properly today because no good models exist for them. Some cancer cell types cannot grow in mouse models nor freely in the laboratory, but they do in our mini-bones, where we can study them. We can do this for bone marrow and blood cancer emerging in our bones in general, using cancer cells isolated from the patients. This provides a personalised platform to study the cancer development of a given individual,” explains Paul Bourgine.
Analysing the biology behind metastasis
In addition to studying the bone-specific types of cancer, the researchers can also learn about the diseases that start elsewhere in the body but then metastasise into the bones.
Examples include breast cancer and brain cancer, and when they metastasise into the bones, the prognosis is very poor.
“We can isolate the different types of cancer and determine why they grow so well in the bones. If we can analyse the mechanisms, we may also be able to develop drugs to prevent this from happening,” says Paul Bourgine.
Paul Bourgine sees great pharmaceutical perspectives in the mini-bones. Many diseases are related to excessive or insufficient production of various blood cells.
These diseases all originate in the bones, and by studying the genetic expression in the cells that produce various types of blood cells, researchers can obtain insight into how to influence the cells with drugs to be more or less active and thereby cure the given disease. Examples include polycythaemia or aplastic anaemia, in which the production of blood cells is too high or low.
A step towards personalised medicine
A different option is to grow cells from a person with cancer in the mini-bones and then investigate how different types of treatment affect the specific type of cancer. This enables doctors to identify the most effective treatment for the individual type of cancer before giving it to the patient.
“Our ambition is to use our model as a personalised medicine platform, so that we can differentiate the treatment for each individual. There is a huge need to be able to provide the best individualised treatment,” explains Paul Bourgine.
Finally, Paul Bourgine also sees potential in bone transplants.
The cells can be removed from the pieces of cartilage with which the researchers work. This means that the immune system does not attack the piece of cartilage when it is transplanted into mice – or humans – to replace something that has been destroyed.
“Further, the pieces of cartilage can produce fantastic bone growth that can replace damaged bone, and they can do this without immunosuppression. This is a whole third potential breakthrough in the model we developed,” concludes Paul Bourgine.
