Building spare parts
Dr. Ian Rogers and his team are building bioartificial kidneys for transplantation.
A Canadian 2009 report found that while the rate of organ donations has increased significantly in the past decade, it lags well behind the rapidly growing need among Canadians requiring organ transplants for various illnesses.
But scientists are working on ways to make organs more accessible, and to overcome the limitations associated with transplantation. Associate Scientist Dr. Ian Rogers and his team at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital are currently attempting to create a bioartificial kidney that can be used for transplantation.
The process requires careful removal of all cells from within a non-useable kidney, followed by replacement with new, healthy kidney cells derived from stem cells. In doing so, special precautions are taken to maintain the structure of the extra-cellular matrix.
“By removing all of the cells in the non-useable kidney and replacing them with new cells that are a match for the patient, we are using the kidney matrix to help replicate the natural process of organ formation and produce a functional kidney for transplantation,” says Dr. Rogers.
The research was aided by Shawn Chua PhD in his lab who played a large role in working out the process of decellularization of the kidney. In order to limit kidney exposure to harsh treatments, Shawnused a profusion pump attached to the renal vein with a needle that allowed for better decellularization over a short time. He then used the same method to place the stem cells back into the kidney for recellularization.
The team faced many hurdles during the procedure, especially when recellularizing the kidney. “Determining which stem cells would differentiate into the various compartments within the kidney in the correct 3D formation and proper sequence is very challenging,” says Dr. Rogers, who applied his knowledge of engineering pancreatic tissues to this new work in the kidney.
For example, during the pancreas work Dr. Rogers found that stem cells could become functional in the animal after only partial in vitro differentiation. When his team was faced with the challenge of forming specialized structures of the kidney, they looked to their previous work with the pancreas for clues. “We are expecting that the stem cells that have differentiated into immature kidney cells in culture will continue to grow into mature kidney cells once inside the kidney’s matrix,” says Dr. Rogers.
Dr. Susan Quaggin,a Lunenfeld clinician-scientist, Canada Research Chair in Vascular and Metabolic Biology and a leading expert in kidney disease, is a collaborator on the project. “Although our lab is undertaking this project on the kidney, we are primarily a stem cell lab, so having Dr. Quaggin in such close proximity is very helpful for overcoming specific challenges,” says Dr. Rogers.
Although Dr. Rogers studies stem cells from bone marrow for most of his work, the future of this field lies in the use of induced pluripotent stem cells (iPS cells). This method would require taking skin cells from the organ recipient and genetically inducing them to become stem cells that can then be instructed to differentiate into the required organ.
“There is enormous potential for growth using iPS cells,” Dr. Rogers says, noting that in 2010, over 1,200 kidney transplants were performed from kidney donors in Canada. Dr. Rogers emphasizes the importance of this research in increasing the rate of successful organ transplants. “The application of this new method could mean greater survival rates for patients suffering from severe organ damage for various reasons.”