Blood vessels for artificial kidney
One step closer to a full-fledged engineering kidney
NanoNewsNet based on the materials of Wake Forest Baptist Medical Center:
Milestone Reached in Work to Build Replacement Kidneys in the LabRegenerative medicine specialists from Wake Forest Baptist Medical Center are working to create engineered kidneys suitable for transplant patients.
Experimenting with pig kidneys corresponding in size to human kidneys, they have developed the most successful method for maintaining the functionality of renal vessels today. Their work is published in the journal Technology (In Kap Ko et al., Enhanced re-endothelialization of acellular kidney scaffolds for whole organ engineering via antibody conjugation of vasculatures).
"Until now, the kidneys grown in the laboratory were the size of rodent kidneys and, due to the formation of blood clots, functioned after transplantation for only one or two hours," says Anthony Atala, MD, director and professor of the Wake Forest Institute for Regenerative Medicine, the head of the study. "In our conceptual study, vessels in a human-sized pig kidney remained open during a four-hour testing period. Now we are conducting a long–term study, the purpose of which is to determine how long it is possible to maintain blood flow."
The present study is part of a long–term project to use a pig kidney as an auxiliary structure – a framework, or matrix - for growing engineered kidneys for transplantation to patients with end-stage renal failure. With this method, scientists first remove all animal cells from the organ, leaving only its "skeleton", and then sow this three-dimensional structure with the patient's own cells. Theoretically, such an organ should not be rejected by the recipient's body.
The process of removing cells leaves intact a network of blood vessels that can potentially provide oxygen to the new organ. However, scientists have faced serious problems with repopulation by vascular cells of the renal framework and, as a result, with pronounced thrombosis developing within a few hours after transplantation.
To solve this problem, researchers from Wake Forest resorted to a two-pronged approach. First, they evaluated four different ways of introducing new cells into the main vessels of the skeleton and concluded that the most effective technique is a combination of cell infusion with a syringe followed by "pumping" of the vessels by cells for a certain period with an increasing flow rate.
Secondly, they coated the matrix vessels with antibodies that make the vascular wall more "sticky" and increase its ability to bind to endothelial cells. Subsequent evaluation experiments showed that the cellular coating of the vessels was sufficient to maintain blood flow throughout the renal "skeleton".
The final test was the implantation of matrices to pigs weighing from 90 to 110 pounds. During the four-hour testing period, the vessels remained open.
"Our method of seeding cells, in combination with antibodies, improves the attachment of cells to the walls of blood vessels and prevents their separation when blood begins to flow through the vessels," explains lead author of the study In Kap Ko, PhD.
In order to reliably confirm the ability of endothelial cells attached to the vessels to prevent thrombosis, long-term studies are needed. But if successful, this work will significantly bring the day when fully suitable for kidney transplantation can be created in the laboratory, the researchers say.
"The results obtained are a promising indicator that it is quite possible to obtain a fully functional vascular system capable of delivering nutrients and oxygen to the engineering kidneys, as well as to other engineering organs," says Dr. Ko.
The use of pig kidneys as a framework for growing organs for transplants has a number of advantages, including the fact that pig and human kidneys are similar in size. And pig heart valves, devoid of cells, have been safely used in the clinic for more than three decades.
If the effectiveness of the new method of covering blood vessels with endothelial cells that provide unhindered blood flow is confirmed, it will be able to be used in engineering and other complex organs, including the liver and pancreas, which many laboratories are working on.
Portal "Eternal youth" http://vechnayamolodost.ru11.09.2014