Cardiac Tissue Engineering: a heart out of the Petri dish

For patients waiting for donor organs, every day can mean the difference between life and death. Making things even more complicated is the fact that not every organ is a compatible match with the patient. It would mean enormous progress if we could grow organs from the patient's own cells in the lab. That's why patients with heart disease place big hope in tissue engineering. While some things are already possible in this area, other aspects might be an option in the future.

Dr. Markus Krane will deliver a presentation about this topic at this year's MEDICA LABMED FORUM. In the run-up to this event, he sat down with MEDICA-tradefair.com for this interview and talked about cardiac tissue engineering, described its possibilities and revealed the obstacles and challenges that still have to be overcome until an actual application is ready for use.

Dr. Krane, your presentation at this year's MEDICA LABMED FORUM is titled "News on cardiac tissue engineering". What will you be discussing?

Dr. Markus Krane: Cardiac tissue engineering includes technologies that produce three-dimensional tissue structures from pluripotent stem cells. There are different options when you pursue a regenerative approach for the heart. One option is to try and supply the heart with fresh cardiomyocytes by means of single-cell suspensions. Or you use tissue that you have cultivated and grown beforehand.

Which patients are good candidates for this procedure?

Krane: This process could become relevant for patients with cardiac insufficiency (commonly known as heart failure) due to ischemic cardiomyopathy as a result of the patient suffering a heart attack and having lost part of his/her heart function, which ultimately has a negative impact on life expectancy. It could be a possible approach to achieve a genuine de novo regeneration of the cardiac muscle. The cardiac muscle is actually unable to regenerate itself. When an area in the cardiac muscle gets ischemic, a fibrous scar forms at the respective site and prevents endogenous regeneration. That's the way the heart regenerates – by forming scar tissue and not by replacing the damaged heart muscle.

What are the current possibilities in this field? How important is tissue engineering in cardiology?

Krane: It's presently not a pertinent issue in terms of whether patients are receiving actual treatment via this method. That's because these are only preclinical studies at this point.

At the MEDICA LABMED FORUM, I will address the different tissue engineering options to generate a so-called patch on the three-dimensional tissue structure. Those can be ultra-thin slices, which are placed on the heart in hopes that cells will sprout or factors that promote heart regeneration are released. The other option would be to transplant actual thick, beating, three-dimensional tissue cultures. However – as I have pointed out earlier - these are still preclinical developments.

The first clinical trials are in all likelihood soon to be launched in Japan. Researchers there use a certain type of sheet. These are thin cardiomyocyte sheets, that is to say, three-dimensional constructs of pluripotent stem cells that are generated in vitro and then transplanted.

When do you think cardiac tissue engineering will be ready for clinical application?

Krane: There are still a few challenges and obstacles we have overcome. If this is meant to be a clinical application, we still have to decide on the path we want to take. There are different types of pluripotent stem cells. Embryonic stem cells (ES cells) are stem cell lines derived from an early human abortion, that is, at a very early cell stage. They are not immune-compatible. Then there is the induced pluripotent stem cell (IPS) technology. You can generate these pluripotent stem cells directly from the patient you want to treat. The catch is that this is a very complex and tedious process. That means it is not an off-the-shelf solution. You must first create and differentiate the stem cell line. You then have to demonstrate that it is of the highest quality and that your finished product is also of high quality. After you have been able to ensure this over several months, you still have to generate the in vitro patches. It's simply a very time-consuming and expensive endeavor.

Another unresolved issue when it comes to the patches pertains to post-transplant immunosuppression. Even IPS cells can occasionally be rejected, albeit not as strongly as ES cells, which are implanted in quite a different genetic context. The nutrient supply to the implanted patch is not yet secured. The fact that the force of contraction is nowhere near human myocardial contractility presents another problem. As you can see, there are still several challenges and obstacles we must overcome in the coming years until we are nearing a genuine therapeutic product.