Nordic Life Science 1
“I’m pretty sure there is nothing else that exist
s on the market, especially for the repair of skeletal tissue. Defining a new category of tissue-engineering product is very exciting.” Bourgine points out: “You cannot take as much as you want, otherwise you have two problems instead of one,” he says. Unlike these current methods, Bourgine’s engineered tissue is standardized and can be applied to many different patients. Because they are produced from immortalized stem cell lines, the material can be generated in unlimited quantities. Most importantly, the cells are removed from the final product by a step defined as decellularization. That means, once they have generated cartilage in vitro, cells are removed: without cells, there is no immuno-rejection and thus the possibility to implant to any patients. Once implanted, the graft is remodeled into living bone tissue with marrow, replicating the properties of natural bone rather than synthetic substitutes. “The advantage is that our graft is fully engineered in the lab. We’re using stem cells that are immortalized so that they can produce unlimited amounts of this cartilage graft that we engineered, and it’s extremely potent. Once it’s implanted into a defect site, it’s replaced by real bone tissue and not by synthetic materials that don’t carry the same properties as our own bone,” he explains. Lack of standardization and financial hurdles Despite its promise, the field of organ and tissue regeneration faces obstacles. Reproducing tissues with consistent, reliable performance remains a major challenge. “Most approaches take the patient’s own cells, but patient cells will be of different quality depending on age, genetics, or how they are collected. If I treat ten patients with their own cells, I cannot predict in which patient the repair will be successful. This lack of standardization is a big problem in the field,” says Bourgine. Financing is another hurdle. Large-animal studies are expensive, and regulations around which reagents and which models to use are very strict. Bourgine notes: “The problem for us now is financing those last studies. At the moment this is the major bottleneck.” His team is applying for major European grants to bridge the gap between laboratory success and clinical translation. A new category of tissue-engineering product Being at the bleeding edge of innovation comes with an additional, particular set of challenges, as Bourgine has experienced when going through the regulatory process: His solution for regenerating bone is so new it hardly fits into any existing regulatory category. The European Medicines Agency (EMA) has categories for tissue-engineered products – which is in itself a relatively new field. But Bourgine’s tissue does not fit neatly into existing definitions. His team engineers tissues using stem cells, but removes the cells from the final product, leaving behind regenerated bone tissue. “We are defining a completely new type of tissue engineering. The problem is that our product is indeed an engineered tissue, using human stem cells. But once this tissue is formed, we remove the cells from the final product by decellularization. What is left is actually a tissue that is composed of a lot of different proteins and the cells are not there anymore. So we have a graft that has been formed by cells, but then the cells are removed, and this change of paradigm makes the classification of this tissue-engineered product a bit more difficult for the EMA. It could be classified both as a combination of proteins (drug) or indeed a tissueengineered product.” For Paul Bourgine, however, this particular challenge is Paul Bourgine in his lab at Lund University with a tiny piece of human engineered cartilage tissue, which they use to stimulate bone repair. 84 | NORDICLIFESCIENCE.ORG also the thrill: “I’m pretty sure there is nothing else that exists on the market, especially for the repair of skeletal tissue. Defining a new category of tissue-engineering product is very exciting. It may delay the translational process, but I prefer to be delayed and do something innovative than just repeat what others are doing,” he says. NLS R&D // HOT TOPIC