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FAQ

FAQs with Dr. Doris Taylor

What college degree are required to work in the field of Organ Regeneration?

The multidisciplinary nature of the work we do attracts researchers from a variety of backgrounds in the biological sciences, engineering and medicine. I have a BS degree in biology and physical science, a PhD in Pharmacology, and post-doctoral training in molecular biology and cardiology. But in my lab, we have engineers (biomedical and electrical), surgeons, cardiologists, physiologists, and cell biologists. They have PhDs, MDs, master’s degrees, BS degrees and high school degrees.  The specific education and training requirements vary based on the area you are interested in and the role you want to play. However, I would say a universal requirement is the ability to think and be passionate about the work you’re doing each and every day.

Do you see organ or engineering being used more for planned transplants or in more emergency situations?

I see both situations benefiting from this science and technology. Because these organs can be recellularized with an individual’s own cells, the new organs will most likely be used for planned transplantations. If a heart valve or a cardiac patch turns out to work without cells, or if any tissue only requires bathing in cells for a few days, then we could use the method for some emergency transplants, too.

How will doctors choose between using a donor organ vs a bioengineered organ for their patients in need of a transplant?

In regenerative medicine, the plan is to grow organs for all types of patients. If the patient is able to receive an organ from a suitable donor in a timely fashion, then that will most likely be the route taken. However, there are many patients who are waiting for a suitable match or have many other factors that do not allow them to be on a transplant list. We will be able to work with those patients.

It is important to remember that when you get an organ transplant today, you unfortunately are trading one problem for another – because you now have to avoid rejection of the new organ. This is usually managed by taking drugs that help to prevent rejection for the rest of your life.  These drugs can have side effects like high blood pressure, diabetes, and often damage your kidneys and vasculature.

This is why we want to build organs or tissues using your own cells. That way you can not only have a new organ but avoid the need to take rejection-preventing drugs that can cause other problems. If we can succeed in this area, I suspect anyone who needs a transplant but can wait for the time it takes to build one will benefit. That being said, if organ donors exist, I don’t think anyone will say no to that route, which has proven to help so many in life-threatening, organ-failure situations. Having both options available helps to better treat patients needing this critical support.

What organs are most easily bioengineered using your methods? Can all organs be easily bioengineered?

We see this methodology being used for every organ. However, the anatomy and physiology of some organs are much more complex than others. A heart is more challenging and more complex than a liver, for example.  Knowing this, we suspect the liver will be the first bioengineered organ to be transplanted, likely for patients with acute liver failure. Still, all organ types are needed and we hope this methodology will help to address those needs.

Have you been looking into reproducing  other tissues such an intestine or skin?

We can decellularize any tissue that gets a blood supply including intestines, the pancreas and skin.

In our decellularization technique, the extracellular matrix composition and architecture of the tissue we are stripping remains intact. Since both of these components are unharmed during decellularization, we are able to harness the perfect scaffold that nature has already grown for us.  This matrix and scaffolding actually helps to instruct the cells that grow on it and makes sure they organize to grow and become a functional organ.

Tissues, such as intestine and skin, are being developed by some of my colleagues in the field. As I understand, these other tissues work well in low pressure settings such as the right side of the heart, but in high blood pressure settings the thin tissues like intestine and skin tend to fail. That doesn’t mean they can’t be helpful, though; they are being used for wounds and for breast reconstruction. So while simple sheets of tissue like intestine and skin can work really well to address things like burns, they won’t work to build a heart, which is where my lab’s focus is currently.

Do you see any possibility for making bones with the bone marrow already in them?

This is a goal I raised a few years ago. I think it may be possible, but not yet. We have a lot of work to do with organs first. It’s a great question, though.

What is your opinion about using pig organs for a scaffolding to make human organs?

Pig hearts are similar in size and anatomy to human hearts, so they make a suitable donor tissue for building a new human heart for patients in need.  However, other pig organs may not be as suitable. For example, we don’t think pig liver would be quite as good. Other organs beyond a heart could still be viable options, like pancreas, kidney, lung and gall bladder, which are being studied in other labs.

Do you see any applications for this research outside of a medical field? For example I was watching a documentary about growing meat—is this the same?

As we work towards building a new organ, there are many applications of the extracellular matrix. One example is it allows us to develop novel structures that can be used to build “mini” organs. These “mini” organs could be used to screen new drugs and chemicals before moving toward pre-clinical and clinical tests. Other potential uses could be for development of vaccines, living energy sources, biological bioreactors for biomolecules or other factors where cells can generate a product more efficiently, as opposed to being synthetically made.

As for growing meat, it is possible, but as a vegetarian I have to admit this is not something I think about.

Which organs are easier to make and transplant?

Each organ has its own complexity in anatomy and physiology. Organs, such as the liver, have some regenerative capacity already and will most likely be easier to regenerate and then transplant. The heart has little natural regenerative capacity and requires more work to build a truly functional heart for transplantation.

As we work to build a whole heart, we are learning how the pieces can be built, such as the aorta, valves and myocardial patches. These individual pieces can also be grown for transplantation and help to restore part(s) of a damaged heart or an aging heart that has lost its ability to pump correctly.

One of the major hurdles we have to building a whole heart is to identify the number of cells and type of cells needed. In building the heart, we believe we will need hundreds of billions of cells, including blood vessel cells, nerves, underlying fibroblasts and cardiac muscle cells. These cells have to assemble into the correct organization and then relearn to communicate with each other appropriately and work in concert to function as one whole organ.

Learning to create whole organs that are more complex, like the heart, will take more time than an organ that isn’t as challenging to produce, like a liver. However, we are making positive progress.

What are the challenges in building an organ?

Cells are a huge hurdle. We estimate it requires hundreds of billions of cells to build a whole heart. Another challenge is keeping the organs alive and sterile in the lab while they develop. The organs don’t have an immune system, so keeping them clean, “free of microbes” or  “free of microorganisms” is a big deal.

How did you discover the right solution for stripping the organs of cells?

There is a lot of research on how to remove the cells without damaging the extracellular matrix. Methods include both mechanical and chemical solutions, and the chosen method depends on the organ of interest.

For the heart, we use an anion detergent solution. We tried several detergents (soaps) for stripping cells, and ultimately we settled on one called sodium dodecyl sulfate (this is the main ingredient in shampoo). We developed a protocol for decellularizing which reduces the amount of DNA present while preserving the glycoaminoglycans (GAGs) and mechanical and structural properties. A review article was recently published by my group that describes a lot of the decellularization processes being investigated worldwide.

(Also see Nature New Feature | Tissue engineering: How to build a heart)

What are the side effects of this method of transplant, if any.

We are still in the research phases of our work, so we don’t yet know what potential side effects could occur. We have to build organs that can survive long term, function properly (i.e. do the normal work assigned to that organ), and have the ability to effectively respond to injury. If any of these three things are lacking in some way, this could result in a side effect.

Our moonshot goal is to develop a heart that is made up of the patient’s own cells. In theory, this will prevent the chance of the patient’s body rejecting the heart. However, as more is learned about stem cells, it may very well be that cells from young healthy donors are the better source.  If this is the case, we will still need to address the same rejection issues we face today when we transplant organs (i.e. the patient must take medicines to suppress the immune system so that their body does not reject the organ).

Until we know more and are further along in the research, it’s too soon to tell what, if any, side effects we’ll have with this method of transplantation.

How do you plan to test this in clinical trials?

Before we can move to clinical trials, organs will be investigated in pre-clinical trials with large animals to test safety and efficacy.

Do you believe that the issues involved with organ transplantation can be solved through stem cells and tissue engineering?

Many issues associated with organ transplantation absolutely can be solved through stem cell and tissue engineering. For example, cell therapy is a regenerative medicine strategy that can be used to intervene early after an injury occurs to treat the underline injury rather than the symptoms associated with the injury and potentially prevent the need for organ transplantation. In addition, tissue engineering provides an opportunity to repair or replace injured organs and tissue. Regenerative medicine is a new field that for the first time has the opportunity to address the major underlying issues that cause disease rather that simple treat the symptoms

What role do stem cells play in your tissue engineering research?

Stem cells are a major component of tissue engineering. Basically, stem are cells that can do two things: first make more of themselves or self-renew or second differentiate into multiple kinds of cells. In tissue engineering we typically combine some sort of material a scaffold if you will, or some other material with cells to build a new structure that allows those cells to function at a sight of injury or disease. Or we use some sort of engineered material to deliver cells in a new way to region of damage.

What new significant discoveries have led to breakthroughs in your research?

Breakthroughs in my research have really come: 1) with an understanding of how to manufacture or scale up stem cells, 2) with the whole idea of decellularization of complex organs and tissues and 3) with the findings about abilities to transplant stem cells or the chemicals or microRNAs or other compounds of stem cell secrete without even needing the cells themselves.

How close do you think we are to being able to engineer and transplant human organs?

Building new bioreactors, finding ways to grow enough cells (billions of) finding how to derive stem cells from an adult individual, and the advent new materials that can be used for scaffolds are all significant contributions to our research. As for how close we are to being able to engineer and transplant human organs, well it depends on the organ, Dr. Tony Atala will tell you that he’s already transplanted most of a bladder, a simple balloon; but transplanting a more complex organ such as heart, liver, lung, kidney is still several years away.

Have a question? Email Dr. Taylor and the Regenerative Medicine Research team at RMR@texasheart.org