Decellularization as a Way to Expand the Donor Organ Pool

It isn't widely appreciated that many of the organs donated for transplant are discarded as unsuitable. In the near future tissue decellularization will be used to expand the pool of viable organs, though it may also lead to enabling xenotransplantation of organs farmed from pigs or other large animals, a step that would largely remove present limits on available organs. In the longer term decellularization and donor organs, human or animal, will be replaced by the growth of complex tissues such as whole organs on artificial scaffolds or completely from scratch, starting only with cells. For now, however, decellularization is the hot topic:

Researchers report progress in their quest to build replacement kidneys in the lab. The teams' goal is to make use of the more than 2,600 kidneys that are donated each year, but must be discarded due to abnormalities and other factors. The scientists aim to "recycle" these organs to engineer tailor-made replacement kidneys for patients. The process begins by washing the discarded organs in a mild detergent to remove all cells. The idea is to replace these cells with a patient's own kidney stem cells, making a tailor-made organ that would not be rejected and wouldn't require the use of powerful anti-rejection medication. But are the organs a suitable platform for engineering after going through the process to remove cells?

To help answer that question, the researchers evaluated whether the washing process affects a small sac of capillaries in kidneys called the glomerulus. The researchers screened the kidney structures to see if they retained growth factors that play an important role in function. The research team reports that the size, structure and function of the micro-vessels in the glomerulus are preserved after the cell-removal process. In addition, vital proteins known as growth factors that regulate cell growth and function are retained within the kidney structures. "These growth factors play a vital role in the formation of new vessels and kidney cells. The fact that they are preserved means they can potentially facilitate the repopulation of cells into the structure and reduce the potential of clot formation."

In a separate study, the team reported on the interactions that occur when stem cells are placed on kidney structures that have been through the cell removal process. The team seeded stem cells derived from amniotic fluid onto sections of kidney structures. In this first study to describe the long-term results of this process, the scientists observed that the stem cells proliferated when placed on the structures and were functionally active as demonstrated by the fact that they secreted chemicals and growth factors involved in such critical pathways as inflammation and the formation of new blood vessels. "These results indicate that discarded human kidneys are a suitable platform for engineering replacement kidneys and that when cells are added, the structures behave as an effective and viable biosystem."