Researchers have made a potential breakthrough in kidney regeneration, finding a successful method to prevent severe blood clots commonly seen after transplantation of the lab-grown organs.
Scientists at Wake Forest Baptist Medical Center worked with human-sized pig kidneys to develop a method to keep blood vessels in lab-grown kidneys open, allowing blood to flow through them.
"Until now, lab-built kidneys have been rodent-sized and have functioned for only one or two hours after transplantation because blood clots developed," senior study author Dr. Anthony Atala, director and professor at the Wake Forest Institute for Regenerative Medicine, said in a press release. "In our proof-of-concept study, the vessels in a human-sized pig kidney remained open during a four-hour testing period. We are now conducting a longer-term study to determine how long flow can be maintained."
The research was reported in the journal Technology and is part of a long-term project to use pig kidneys to create “scaffolds,” or support structures, that may one day be used to build replacement kidneys for patients with end-stage renal disease. By removing all animal cells from the kidneys, scientists are left with a “skeleton” organ structure where they could then place a patient’s own cells to make a kidney, thereby reducing the risk for rejection.
Until now, maintaining blood flow to the new kidneys has been a hurdle for scientists employing regenerative techniques, resulting in severe blood clots just hours after transplantation.
To address the problem, Wake Forest Baptist researchers first evaluated four different methods of inserting new cells into the blood vessels of the kidney scaffold. They found that combining two methods -- infusing patient cells into the organ with a syringe, and then pumping cells through the vessels at increasing flow rates – was most effective.
Scientists then coated the blood vessels with an antibody designed to make them bind endothelial cells and did imaging studies and flow tests to make sure the cell coverage would support the flow of blood through the entire scaffold. When they implanted the engineered scaffolds in pigs weighing between 90 and 110 pounds, study authors observed that the vessels remained open throughout the entire 4-hour testing period.
"Our cell seeding method, combined with the antibody, improves the attachment of cells to the vessel wall and prevents the cells from being detached when blood flow is initiated," said In Kap Ko, lead author and instructor in regenerative medicine at Wake Forest Baptist.
Study authors noted that long-term studies still need to be done to prove the success of the new method. But the initial research is exciting for the future of regenerative medicine as it opens the door for application to more complex organs like the liver and pancreas.
"The results are a promising indicator that it is possible to produce a fully functional vascular system that can deliver nutrients and oxygen to engineered kidneys, as well as other engineered organs," Ko said.