Right now, most human organs that are surgically implanted in patients come from donors.
That is, the needed organ, like a liver (or part of a liver) is removed from the donor (either living or dead) and surgically implanted into the recipient. Once transplanted, the patient needs to be kept immunosuppressed to insure that the organ is not rejected. And the chemical immunosuppression that takes place can have consequences in the recipient, since it leaves him immunocompromised. With his immune system weakened, he may be more prone to various types of infections, often opportunistic infections, and can leave him open to a higher risk of developing cancer.
Growing and transplanting a human trachea
Recently a trachea (windpipe) was produced in a laboratory and transplanted into a recipient.
The patient had a tracheal cancer. The cancer had recurred after surgery, radiation and chemotherapy. The tumor had grown large enough that it was beginning to obstruct the trachea. Doctors could have transplanted a donor trachea, but they chose to bioengineer one.
They used a polymer framework as a skeleton. It mimicked the size and shape of the trachea. Then they bathed it in tissue culture medium in which the patient’s own stem cells were placed. The stem cells were stimulated to form the appropriate types of cells to line and cover the trachea by being exposed to specific chemicals that cued the stem cells to develop into the required tissues.
Once that part of the bioengineering process was complete, the trachea was transplanted into the patient. Since the trachea was populated by the patient’s own cells, he would not need to be treated with immunosuppressive medications. The surgery was successful. (Since the initial surgery, a few more trachea implants have been done.)
Other replacement organs have also been produced. But they are very basic types of organs, like a urethra. But these organs are very simple in that they are basically just functioning tubes. The trachea and urethra are tubes, although they do have some other functions. What about more complex organs that have a wide variety of different cell types and functions?
The liver is a much more elaborate organ than a trachea. It has a number of different cell types, and those cells do a wide variety of tasks. Often these tasks are the synthesis of a large number of chemical compounds.
Using cells to reconstitute your own liver, instead of using a transplant
For example, the liver is responsible for making cholesterol. The liver cells carry out a number of biochemical reactions to produce cholesterol and many other needed products. The liver also acts to remove some chemicals from the blood and detoxify them. In the past, and for now, a failing liver had to be replaced with a liver (or part of a liver) from a donor. In the following study, researchers repaired ailing livers in mice.
These scientists used human cells. The wanted to see if they could cause human cells from another tissue (not liver) to become liver cells and function as such.
They took human fibrobasts and chemically altered them. They caused them to become a type of stem cell that could be induced to become a functioning liver cell (hepatocyte). These cells were then transplanted into mice that were suffering from liver failure. These human hepatic cells repopulated the mouse livers and functioned as natural liver cells.
While this research has only been done using human cells transplanted into mice, it opens up the possibility, that with years of additional research and testing, cells taken from a patient with liver failure might be induced to become hepatocytes. These hepatocytes, when given to the patient might eliminate the need for transplantation and live-long immunosuppression with drugs.
Growing a lung
Other researchers have grown complex organs like lungs.
Scientists at the University of Texas at Galveston have produced a prototype of a human lung. They used a damaged human lung as a scaffold after stripping away all of the cells, just leaving a framework of cellular material like collagen (a structural protein).
Next they took lung cells from the less damaged of the pair of lungs and put these cells and the scaffold in a tank of tissue culture medium. After about 4 weeks, the cells had covered the scaffold and produced a lung, though with some differences from normal lungs. [Note: these lungs have NOT been tested to see if they are functional. So this is very preliminary research.]
The scientists plan to eventually test the bioengineered lungs in pigs to see if and how well they might work. So any possibility of using these in humans, even if all of the studies show that the lungs work well, would still be many years in the future.
Additionally, researchers might be able to use polymer skeletons, much as was done in the trachea work, to allow the new lungs to grow outside of the patient’s body as he waits for the implant.
If the patient’s own lungs are too damaged to supply enough normal lung cells to repopulate the lung skeleton, human stem cells have been manipulated to become lung cells and these might serve as the tissue to invest the skeleton.
Other, similar research is underway looking at bioengineering other organs that can then be used for organ replacement. Possibilities are bioengineered pancreases, hearts, intestine and others.
Benefits of producing our own organs
What are the benefits of using organs produced in this way? There are several.
1. Statistics show that about 20 patients die each day while waiting for the appropriate organ. If bioengineered organs can be produced, this number may decrease tremendously. Of course, that would depend on a number of factors: speed with which the organ can be grown, availability, cost, etc.
2. Organ harvesting surgeries would decrease. Now organ harvesting drives up the cost of transplants. Bioengineered organs would eliminate harvesting.
3. Some organs could be repaired without surgery to the “recipient.” For example, in the mouse liver experiment, the human hepatocytes were injected into the mouse. If similar techniques can be used in humans, then invasive surgery in some cases, may be avoided.
4. When a donor organ is used, there is always a slight risk that the donor may have an infectious disease that was not detected. Or the organ may contain a small cancer that is not obvious during examination. In the case of a pathogen, this could infect the patient. If a cancer is present, it could grow and spread after transplant.
5. If the bioengineered organ is made from the patient’s own stem cells, then immunosuppression would be unnecessary. The new organ would be genetically identical with the recipient, so no need for immune suppression therapy as would be required if a donor were involved. If the patient isn’t immunosuppressed, then the risks for developing an infection or cancer are much reduced.
Of course there are downsides too. Much more research (and funds for that research) will need to be done for each organ type. And the cost of growing an organ through a process of tissue culture is quite expensive. Almost certainly, if perfected, the work would be labor intensive, slow (weeks to months) and the people involved would need special skills. And studies will need to be done to insure that the organs are biologically fit enough to be beneficial for the patients’ use. Virtually none of the work, at it’s current stage of development, will benefit any patients currently on transplant lists.
We’re still in the early stages of organ bioengineering, just breaking new ground and exploring options. Routine use of these techniques, if they prove successful in humans, may be a decade or more in the future. But the ideas and techniques are exciting and challenging. And the next few years of work in this field should be very interesting.