For the first time, scientists from Scotland have reported that an entire, functional organ has been grown from scratch inside a laboratory animal. A Scottish research group successfully transplanted a small quantity of cells into a laboratory mouse that grew and developed into a functional thymus.
These findings were published in the journal Nature Cell Biology, and might open the door to new alternatives to organ transplantation. This research certainly shows great promise, but is still years away from clinical trials and reproducible human therapies.
If you are wondering what the thymus is, it serves as an integral part of the immune system. The thymus is located just above and slightly over the heart and produces a vital component of the immune system, called T-cells, which fight infections and regulate the immune response.
A research team from the Medical Research Council Centre for Regenerative Medicine at the University of Edinburgh began this experiment with mouse embryonic fibroblasts. These fibroblasts are found in the skin and connective tissue of the embryo. These mouse embryonic fibroblasts were genetically engineered to expressed the FOXN1 gene, which encodes a transcription factor known as the “forkhead box N1″ protein. The forkhead box N1 protein binds to DNA and activates the expression of genes necessary to make thymic epithelial cells. Mice that do not have a functional copy of the FOXN1 gene a “nude” mice. They are nude because they have no hair and have no thymus.
Once engineered to express FOXN1, the fibroblasts began to differentiate into thymic epithelial cells. The Scottish team mixed these genetically engineered fibroblasts with some other support cells and transplanted them into laboratory mice where they summarily formed a fully functional thymus. Structurally the animal-grown thymus contained the two main regions – the cortex and medulla – and it also produced T-cells.
Prof Clare Blackburn, who was part of the research team, said it was “tremendously exciting” when the team realized what they had accomplished. Blackburn told the BBC: “This was a complete surprise to us, that we were really being able to generate a fully functional and fully organised organ starting with reprogrammed cells in really a very straightforward way. This is a very exciting advance and it’s also very tantalising in terms of the wider field of regenerative medicine.”
Such a procedure could benefit patients who need a bone marrow transplant and children who are born without a functioning thymus. Likewise because our immune response diminishes as we age and out thymus shrivels, such a procedure might boost the waning immune system of aged patients. could all benefit from such a procedure.
However, there are a number of problems to solve before this procedure can cross the bridge from animal studies to hospital therapies. First of all, the recipient of these implants were nude mice that had no thymus and could not reject transplanted tissue. Also, the use of embryonic fibroblasts would cause a robust immune response against them. Some other cell type must be found for this procedure that grows robustly and does not cause transplantation rejection.
Researchers also need to be sure that the transplant cells do not pose a cancer risk by growing uncontrollably. Prof Robin Lovell-Badge, from the National Institute for Medical Research, said: “This appears to be an excellent study. This is an important achievement both for demonstrating how to make an organ, albeit a relatively simple one, and because of the critical role of the thymus in developing a proper functioning immune system. However… the methods are unlikely to be easy to translate to human patients.”
This experiment is a testimony of just how far the field of regenerative medicine has come. Already patients with lab-grown blood vessels, windpipes and bladders have benefited from advances in regenerative medicine. These tissue engineered structures have been made by “seeding” a patient’s cells into a scaffold which is then implanted. The thymus in this case only required one injection of a cluster of cells. While it is doubtful that other organs will be this easy to grow, it is an encouraging start.
Also, this experiment utilized “direct reprogramming” that did not require taking cells through the embryonic stage. Instead one-gene reprogramming directed the cells to make thymus epithelium cells. This almost certainly promises to be a much safer way to make cells for regenerative treatments.
Dr Paolo de Coppi, who pioneers regenerative therapies at Great Ormond Street Hospital, said: “Research such as this demonstrates that organ engineering could, in the future, be a substitute for transplantation. Engineering of relatively simple organs has already been adopted for a small number of patients and it is possible that within the next five years more complex organs will be engineered for patients using specialised cells derived from stem cells in a similar way as outlined in this paper. It remains to be seen whether, in the long-term, cells generated using direct reprogramming will be able to maintain their specialised form and avoid problems such as tumour formation.”