5 minute read
SORE JOINTS? CONSULT A TISSUE ENGINEER.
Athletes, dancers, people with heavy work or who are overweight, the elderly, accident victims ... all have increased chances of joint pain caused by damaged cartilage. Since our body cannot repair this damage itself and there is a shortage of donor tissue, Hannah Agten, postdoc in the Biomaterials & Tissue Engineering Team at Group T Campus, set out to find replacement tissue. In her PhD, she studied lab-grown cartilage tissue.
Creaky cars run the longest, says the proverb. The same cannot be said of creaking joints. On the contrary, there is a special tissue at the ends of our bones that is precisely to prevent direct contact in the joints. “This tissue is not called cartilage by chance”, Hannah explains. “You can compare it to a cushion that prevents friction and pressure so that you can move painlessly and make physical efforts. Joint cartilage that is damaged needs to be treated because the pain does not go away by itself.” Three methods are currently used. The first uses cells from the patient’s bone marrow to make new cartilage tissue. “This seems an obvious choice, but in practice these cells produce an inferior, fibrous substance. Moreover, it increases the risk of osteoarthritis, which amounts to even further deterioration of the joint”, says Hannah.
A second option is transplantation of cartilage tissue from the patient or from a donor. “However, when taking tissue from the patient, you create a new lesion. With donor tissue, there are large differences in quality and the risk of rejection is real. For severe defects, a prosthesis can provide relief. This is the third option. Unfortunately, the lifespan of prostheses is limited, making them less suitable for younger patients.”
Tissue from the lab
The alternative is to make your own tissue in the lab. “This technique is called tissue engineering”, Hannah continues. “This uses cartilage cells and a water-like gel (hydrogel) that resembles cartilage tissue. This gel is based on gelatine, which is a derivative of the body’s own protein collagen that healthy joints are mainly composed of. When you place those cells in an environment that resembles natural tissue, they are stimulated to produce new healthy cartilage. This method does not have the disadvantages of donor tissue or prostheses and is therefore promising for healing joint injuries.”
How do you make tissue in the lab? “The basic ingredient are functional cartilage cells. Taking these from the patient’s body is not an ideal solution. If you take too many, you create an additional cartilage defect. If you take too few, the cells will ‘dedifferentiate’ and ‘forget’ what they are supposed to serve for. A possible alternative is to use stem cells from the bone marrow that are stimulated to become cartilage cells. For the patient, this means a painful procedure. Moreover, this method offers no certainty about the quality of the newly formed cartilage”, Hannah said.
New solution
To overcome all these obstacles, Hannah uses a new technique: that of ‘induced pluripotent stem cells’ (iPSC). “These are body cells (from a donor) that are first ‘reset’ into stem cells and then reprogrammed into cartilage cells. You can multiply the body cells at will after resetting so that you obtain a sufficiently large quantity. These cells produce high-quality cartilage and cause significantly fewer rejections than donor tissue. It is an efficient and effective way to regenerate cartilage tissue.”
In her research, Hannah has experimented with different amounts of iPSC cartilage cells. She succeeded in selecting an optimal quantity to produce cartilage tissue in the lab. But is this product from the lab also usable in practice? “I tested that in rats”, Hannah replies. “The tests showed that cartilage formed with both fresh cells that were only recently in the gel and cells in gel that had already formed tissue in the lab for three weeks. Finally, in 1 of 4 animals with incurable cartilage lesions, we managed to grow new cartilage based on the hydrogel.”
This immediately led to the question: why did no healing process occur in the three other rats? It turned out that this had everything to do with the size of the implants, which was not fully matched to small defects in the animals’ knees. To solve this problem, Hannah turned her light to bioprinting technology. This allows you to use the cells in the gel as biological ink to 3D-print implants in any desired shape. Tests showed that the printed cartilage had the same quality as what had been grown in the lab.
“The next step is to try out the printed cartilage implants in real joint injuries,” says Hannah. “It is already clear that 3D bioprinting technology can provide a real breakthrough in the field of tissue engineering. It will even be possible to make patient-specific implants based on MRI scans in the foreseeable future. With this, the way is open to tailor our cell-gel implants even better to the patient and boost the chances of cure to 100%. What was incurable until recently will soon be completely curable.”
To be continued
Currently, Hannah is conducting follow-up research with a company to further improve the hydrogel with a view to 3D bioprinting. “Intensive collaboration between the academic and corporate worlds can accelerate the process towards effective clinical treatment of cartilage defects”, Hannah believes. “The number of people we can relieve from joint pain this way is uncountable. Tissue engineering is a profession with a future.”
Yves Persoons
