Developing a Recellularization Approach to Produce Thymic Tissue

The thymus produces the T cells that make up the adaptive immune system, but the organ atrophies with age, contributing to the age-related decline of immune function. A popular science article here comments on a new biotech company seeking to produce thymus tissue for transplantation from decellularized donor tissues. This builds upon work of recent years that improves the understanding of the stem cell and progenitor cell populations that give rise to thymic tissue. Given that understanding, it should be possible to take decellularized thymic tissue and repopulate it with patient-derived cells, or from novel universal cell lines that have been altered so as to allow transplantation into any individual with minimal risk of rejection. While it seems likely that the company will, at the end of the day, remain focused entirely on children born without a thymus rather than on the age-related loss of thymic tissue, there is certainly that potential application waiting in the wings for someone to take up the flag and run with it.

"The thymus had largely been ignored because it's complicated, and historically understanding of the biology had progressed slowly. It's starting to accelerate now and a lot of the work that the Francis Crick Institute has been doing is aimed at understanding the core stem cell niche of the thymus and use this to recreate thymus biology. Until recently, there was uncertainty around the progenitor stem cell that leads to the epithelial cells that gives the thymus function. The Crick researchers discovered novel progenitor cells and Videregen has licensed the resulting patents, which give us the basis of the cell biology. That allows us to build a better functioning thymus from scratch, because we understand the cell biology better than anyone else."

The initial indication for Videregen's immune program is children born without thymus function, which is called complete DiGeorge Syndrome, but this is only the beginning of the company's work in this area. "The thymus is primarily concerned with two things: the first is to provide T cells, which fight infection and circulate our bodies throughout our life, taking out precancerous cells. Over time, our thymus function decreases, which is why in old age, you tend to get more cancers, you respond less well to vaccines, and you get more infections. So addressing thymus atrophy is a big factor in longevity and aging. At the moment, we're focusing on niche, orphan indications, which means we don't need to industrialize to a big scale - we're talking about hundreds or thousands of patients, not millions. But when we get to those kinds of scales of populations, we will need the technology to be able to deliver a mass-produced tissue."

Videregen's approach is built on the company's expertise in decellularization - the process used to isolate the extracellular matrix of a tissue from its inhabiting cells, leaving only a "scaffold" of the original tissue. This scaffold can then be seeded with appropriate cells to enable organ and tissue regeneration. "We've learned that the biology of the extracellular matrix is really important - it isn't just structural. If you preserve the biology well, you get better infiltration of cells, better vascularization, and better repair and function over time. This is achieved by controlling the way the tissue is processed and decellularized - the more natural the better."