Bioengineered organs may redefine transplants for humans someday, and even allow damaged organs to regenerate.
Northwestern University researchers are in the beginning stages of bioengineering tissues and entire organs from stem cells of adult rats and mice, said Dr. Jenny Zhang, who directs the Microsurgical Core within the Comprehensive Transplant Center at Feinberg.
Once engineered, Zhang said her team will be able to test the functionality of such organs as transplants in the rodents. For now, Zhang and fellow researchers are using a biodegradable scaffold, a kind-of-skeleton of an organ with all living cells removed, to test the model.
By developing a successful animal model, the stage is set for future testing on primates and eventually humans. Zhang said bioengineered organs would significantly reduce waiting times for people needing transplants and prevent rejection of healthy organs.
Researchers also want to gain a better understanding of the cytomegalovirus (CMV), a particular threat to transplant recipients.
CMV is a common virus found in 50-90% of all people, but has a greater chance of being activated after transplantation due to immunosuppression (reduction or complete absence of a healthy immune response or immune system).
The immune systems of healthy individuals are able to fight off the virus or put it in a latent state. Compromised immune systems have a much harder time fighting the virus that can cause respiratory and other health problems.
Zhang talks about her research of ongoing projects and current successful models already established.
You mentioned that the core is working on 10 ongoing projects. What are these?
One of the projects is tissue engineering. For example, an idea in the transplant field is regenerative medicine. If you have a damaged organ, you would want it to regenerate, such as in the case of acute kidney failure. Also, a lot of people are on the waiting list for transplants. There is an organ shortage. We are trying to grow tissues and organs in the lab using stem cells from bone marrow or a particular organ of adult mice. In the future, we hope to take cells from something living and grow them. Normally, you can only grow embryonic stem cells. Now, we can use any cells to become pluripotent, meaning any cell.
Another project deals with the CMV virus. We want to study why this virus is activated after transplant surgery so that we can prevent it. It is one of a couple of viruses that suddenly wake up with immunosuppression. CMV can be transferred via saliva, bodily fluids or through the placenta. Only an active CMV agent can be transferred and is a threat only when activated. A great percentage of the population carry the virus in their bodies but it is latent until activated. Immunosuppression in a transplant recipient can greatly affect a person’s ability to fight off the virus.
What organs have you successfully worked with so far?
So far, we have had success with the kidney, liver, and heart in these animals. Normally, the mouse or rat can survive two surgeries.
Have you been successful in taking the cells out of an organ, infusing new cells, and transplanting a completely functional organ into a mouse or rat yet?
We are in the early stages. What we have been successful doing is removing all the cells from an organ, such as a kidney or liver and injecting new cells, called endothelial cells, on the surface of the organ. We are in the process of testing these organs to see if they can hold blood and function normally.
What have you been able to accomplish thus far with the stem cells?
Our research entails using real organs in whole or part from mice and rats. We use a machine to diffuse the organ and take out all of the cells, leaving a scaffold, skeleton-like structure that looks like a honeycomb. Then we infuse new cells that are grown in a bioreactor. The intention of infusing cells is for them to grow into the desired organ or tissue.
The bioreactor is able to simulate a natural environment where these cells would normally be grown. We are able to monitor the environment and determine the best condition for use. Usually the time the organ spends in the machine can range from 10 days or even longer depending on the type and size of the organ.
What is the significance behind choosing to conduct this research on rodents?
If we can equate an animal model, we can use it for testing a bioengineered organ and see if it is functional, how long the cells with survive, and if it will form a normal structure. In a mouse we can do all sorts of things we can’t do in humans.
Why do you test both mice and rats?
We will test this model on rodents, then primates, and eventually humans. The difference between a rat and a mouse is the size. Rats are 10 times bigger than mice and are easier to work on. We use only inbred rodents. These animals have been studied for years so we know the genetic make-up and can precisely test the type of rejection they will experience.
In how many of the cases will an animal or human experience rejection of an organ?
In all cases, animals and humans experience some type of rejection. In the case of humans, regardless if two people are a complete match, some molecules are bound to be different. Each cell has a molecule on the surface and what is called a major histocompatibility complex, or antigens. Humans are more complicated than animals and with the mice it is much easier to control the immunosuppression response.
How are humans treated when they experience rejection of an organ?
All people are treated and will take medicine for the rest of their lives. The rejection is variable as is the dosage of medicine a person will take. Examples of medicine prescribed include Tacrolimus or Thymoglobulin. For kidney and liver transplants, there is a current success rate of about 90 percent.
How do you infect the rodents with the CMV virus?
We inject the mouse with the virus and let it survive for a couple of months. Initially, it will suffer respiratory problems. Sometimes, it will not happen, because the mouse has cleared the virus from its system. A healthy individual can sometimes clear out the virus, but someone whose immune system is compromised won’t be able to clear it out.
What is the goal of studying rejection?
We are in the beginning stages to test tolerance, or the ability to trick the body into not recognizing the organ as foreign. If we can do that, we can prevent rejection partially or wholly, which can possibly translate to a human.