What is your approach to solve these issues?
Wiegmann: Our idea is to populate all artificial surfaces that trigger foreign body reactions such as the formation of a thrombus with endothelial cells - that means, we populate the hollow fiber membranes and tubing. Endothelial cells line the interior surface of blood vessels in the human body and are hemocompatible, thus preventing thrombus formation. Since the body's own endothelial cells are not available in sufficient quantities, we use endothelial cells that are not endogenous to the body. We genetically modify them, so the patient’s immune system does not recognize them as foreign and reject them. Another option is to use so-called induced pluripotent stem cells to develop an unlimited source of endothelial cells. To recap, we make the artificial surfaces biological with the endothelial cells to create a so-called biohybrid lung, which lasts a lifetime and eliminates the need for anticoagulation.
The goal is to implant an artificial – biohybrid – lung in patients. What are the next steps to make this a reality?
Wiegmann: One step is to ensure that the endothelial cells adhere firmly enough to the hollow fiber membranes. An implanted biohybrid lung would have to withstand the blood flow of four to six liters each minute. The endothelial cells must be able to withstand the frictional stress caused by this blood flow.
Current ECMO systems measure about 15x15x5 centimeters in size, making implantation in the body impossible. This necessitates miniaturization, which should ideally be tailored to the individual patient as each patient requires a different gas exchange surface area to support the lungs depending on the type and stage of the disease. The membrane size enables us to control the biohybrid lung capacity and performance. Miniaturization should therefore keep individualization in mind.
What will the future of artificial organs look like?
Wiegmann: That is an interesting and exciting question. There are parallel approaches to this: We try to use so-called tissue engineering to colonize existing surfaces with endothelial cells. Another approach is to grow organs in a lab. And yet another method combines the two approaches: For example, you can take lungs and use decellularization to isolate the extracellular matrix, leaving lung scaffolds for new cell colonization. You could use human or animal lungs, like the lungs of a monkey for this purpose.
Yet regardless of the research approach, you must have sufficient quantities of the different types of cells in the lung. That is because at this point it is not possible to extract these cells from the patient and grow them in the laboratory. You are forced to use exogenous material and ensure that the body does not recognize it as foreign and trigger an immune response. Otherwise, you would be back at the same point where we are today when it comes to organ transplants: The patient must take medication to prevent rejection and ensure the immune system accepts the exogenous cells. Of course, this is something we want to avoid since our goal is to develop an artificial lung that can be permanently implanted as an alternative to a donor organ.
It remains to be seen which of these fields of research will be the most successful in the future – my guess is that it will be a combination of all these approaches.