These kidneys grown inside the rats from transplanted were not perfect and only externded life for several days. However, one of the scientists likens this first successful attempt to grow kidneys in a mammal to the short first flight of the Wright brothers at Kitty Hawk.
St. Louis, June 21, 2004 -- Growing new organs to take the place of damaged or diseased ones is moving from science fiction to reality, according to researchers at Washington University School of Medicine in St. Louis.
Scientists have previously shown that embryonic tissue transplants can be used to grow new kidneys inside rats. In their latest study, though, they put the new kidneys to an unprecedented and critical test, removing the rat's original kidneys and placing the new kidneys in position to take over for them. The new kidneys were able to successfully sustain the rats for a short time.
"We want to figure out how to grow new kidneys in humans, and this is a very important first step," says Marc R. Hammerman, M.D., the Chromalloy Professor of Renal Diseases and leader of the study. "These rats lived seven to eight days after their original kidneys were removed, long enough for us to know that their new kidneys worked."
The study will appear in the July/August issue of Organogenesis, a new scientific journal. It is also available online.
Hammerman is a leader in the burgeoning field of organogenesis, which focuses on growing organs from stem cells and other embryonic cell clusters known as organ primordia. Unlike stem cells, organ primordia cannot develop into any cell type--they are locked into becoming a particular cell type or one of a set of cell types that make up an organ.
My guess is they are getting these organ primordia cells by letting an embryo develop further than the initial stem cell stage. Using human organ primorida cells would likely elicit much stronger ethical objections than using embryonic stem cells since the fetus would need to develop to a later stage before being aborted to use its tissue for this purpose. Still, even if this approach was not allowed in practice this research is still going to yield important information for other approaches.
"Growing a kidney is like trying to construct an airplane--you can't just make a single part like a propeller, you have to build several different parts and systems and get them all working together properly," Hammerman explains. "Fortunately, kidney primordia already know how to grow different parts and self-assemble into a kidney--we just have to give them the right cues and a little assistance at various points."
For the study, Hammerman and coauthor Sharon Rogers, research instructor in medicine, gave renal primordia transplants to 5- and 6-week-old rats. Prior to insertion, scientists soaked the transplant tissue in a solution that included several human growth factors, proteins and hormones. One of the rats' original kidneys was removed at the same time.
Three weeks after the transplant, researchers connected the new kidneys to the bladder and administered a second dose of growth factors.
Approximately five months after the transplants, scientists removed the remaining original kidney in control and experimental rats. To help resolve uncertainty about which kidney functions are critical to sustaining life, scientists cut the connections between the bladder and the new kidneys in a subset of the experimental rats.
Rats with no new kidneys lived for two to three days, and rats whose new kidneys were disconnected from their bladders lived no longer. However, the rats with new kidneys connected to their bladders lived seven to eight days.
"This tells us that the urine-producing functions of the kidney are key to preservation of life," says Rogers.
"Seven to eight days may not seem like a long time," adds Hammerman. "However, what we have done is akin to building the first airplane and showing that it can fly, if only for a few minutes. It's just as revolutionary."
Hammerman's goal of using pig cells to grow kidneys in humans would sidestep ethical opposition to the use of human stem cells and human embryos.
Hammerman, who is director of the Renal Division at the school's affiliate Barnes-Jewish Hospital, hopes to use animal-to-human transplants, known as xenotransplants, as a solution for chronic organ donation shortages.
"Every year, approximately 10,000 kidneys become available for transplant into patients with end-stage kidney disease," Hammerman says. "But the waiting lists for kidney transplants can run as high as 100,000 individuals, and most patients die of the disease before an organ becomes available."
Kidney function in pigs is similar to that in humans, and Hammerman's eventual goal is to use embryonic pig tissue transplants to help renal failure patients live longer.
Would Jews or Muslims who will not eat pork also object to having a pig kidney grown inside them?
The vascular system that grows for these embryonic kidneys appears to be partially or fully made from host cellls that serve as precursors for formation of blood vessels that then grow into the shape needed for the kidneys. That explains why the use of early stage transplants would avoid immune rejection via an attack on the vascular system. The vascular system is not foreign tissue even though the actual kidney cells are foreign.
Working with embryonic tissues that grow into organs inside the patient lets Hammerman avoid hyperacute and acute vascular rejection, two immune system responses that can destroy xenotransplants. In both of these responses, the body's immune system recognizes the blood vessels of transplanted tissue as foreign and attacks them.
"Those two types of rejection have so far made it impossible to xenotransplant fully grown kidneys," Hammerman explains. "However, we can avoid this by transplanting embryonic kidneys before blood vessels develop."
The primordia are small enough that survival can be maintained after transplantation through diffusion of oxygen and nutrients. The transplanted cells attract the growth of new blood vessels from the host as they grow into a mature organ.
This approach of using organ primordia cells may avoid the immune system rejection of the vascular system in the kidneys but will it avoid the immune system's eventual rejection of the pig kidney cells? If one could grow kidneys from one's own adult stem cells then the immune rejection problem could be avoided.
We really need a number of different organ growth capabilities. The ability to grow an organ ahead of time outside of the human that can be put into any body would allow replacement organs to be used in acute emergencies (e.g. after a bullet has shredded a heart). Such an organ would not necessarily have to be perfectly immune compatible. In an emergency immune suppression drugs could suppress the immune response while a more immuno-compatible replacement organ was grown.
This approach reported above both requires the host to grow the organ and may not yield a perfectly immune compatible organ. Still, artifiical kidneys have deficiencies that eventually result in death and with time we will have better techniques for coaxing a body's immune system to treat an organ as compatible. This approach might end up working for many puposes until a more ideal approach is developed.
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