Lung regeneration

A scratch on your arm, a graze or a bruise: the skin is usually repaired within a few days. But unlike other organs, the damaged lungs in COPD are no longer capable of repairing or renewing damaged tissue. Can we get this repair process back on track?

The Consortium Lung Regeneration researches the possibilities of the lungs being able to repair themselves or replace damaged lung tissue. The Consortium is led by Prof.dr. Hans Clevers (Hubrecht Institute, Netherlands) and Prof.dr. Carla Kim (Harvard Medical School / Boston Children's Hospital).

With COPD the alveoli break down, the walls are so damaged that they can no longer do their job. Stem cells play a key role in this process. Normally stem cells repair damaged tissue, but with COPD the damage is so protracted and chronic that the stem cells seem to be exhausted. As soon as it is clear where things go wrong, treatments can be developed. For example, with cultured stem cells or by administering medicines to reactivate stem cells. And that brings the curing of COPD closer by.

The Consortium Lung Regeneration encompasses four promising sub-projects. Within each sub-project, highly specialized top institutes are working on a specific assignment. Major steps are made with intensive international knowledge sharing.

  • Lung Organoids

    The fact that scientists have succeeded in growing mini organs (organoids) in the laboratory is a giant leap forward. This state-of-the-art technique brings a medical breakthrough closer.

    Until recently, researchers in the laboratory worked with single cells. There was, unfortunately, no other option for fundamental research. That was making do, because individual cells cannot mimic the function of an organ. Furthermore, they do not live for long.

    The invention of the so-called organoids by the Hubrecht Institute in Utrecht was a crucial breakthrough in scientific research. Organoids are mini organs, grown from stem cells. These three-dimensional lab models of, for example, a bowel or liver look exactly like a real organ in terms of structure and physiology. And that offers unprecedented opportunities for targeted scientific research.

    Consortium researchers have already been able to create a mini trachea  and are now aiming at creating an organoid of alveoli. With that will come very specific answers to the question of why alveoli no longer repair themselves in COPD sufferers. It will also make it easier to test medicines and methods for reestablishing the repair process. In this way, organoids accelerate the research and bring a solution for COPD closer by.

  • Sub-project 1: Repairing the lung barrier

    The lung is a very complex organ and it is thus a challenge to identify the different cells and their functioning. And even more important: Which types of lung cells are capable of repairing damaged lung tissue?

    The lungs are in direct contact with the outside world and are therefore vulnerable. In this sub-project, the researchers look at the cells that line the bronchi, also called the epithelial cells. This outer cell layer in the bronchi forms the barrier with the outer world. Smoking or air pollution damages these cells.

    Stem cells are known to have the potential to create new tissue. Scientists are studying epithelial stem cells to see if they can do the same. The next step is to expose their growth and development process. After all, once these processes have been unraveled, it will also be possible to control them.

    That is not the end of the matter. The researchers are developing a technique to allow epithelial stem cells to grow on grafts. The aim is to make a fully functional piece of bronchi lining.

  • Sub-project 2: alveoli from the lab

    With COPD, the alveoli break down and are no longer replaced. The solution sounds simple: ensure that alveoli are repaired or replaced. But how can we achieve this? The researchers are addressing this by examining the structure and functioning of the alveoli.

    Alveoli ensure that the blood absorbs oxygen. In the event of COPD, the alveoli are broken and the walls are so damaged that they no longer work properly. As a result, it becomes increasingly difficult to absorb oxygen and COPD patients feel they are suffocating.

    In this sub-project, the researchers fully map out how alveoli repair and renew themselves. This is done by identifying and characterizing the stem cells of the alveoli. Stem cells can after all produce new tissue.

    The next step is to make a mini-organ (organoid, page 8) of the alveoli, grown from the stem cells of alveoli. With this innovative technique, medicines for lung repair can be tested much better in the laboratory. Thus the search for a means of stimulating the production of new alveoli can take place more quickly and in a targeted manner. And that can be a breakthrough for curing COPD.

  • Sub-project 3: Self repairing capacity

    In young children, lungs are able to repair themselves. In adults, this possibility has almost disappeared - but not entirely. In this sub-project, researchers are looking for the key to stimulate lung recovery.

    For a long time it was thought that adult lungs could not recover from damage to the alveoli. But it was only recently that scientists discovered new alveoli in a woman after part of her lung had been removed. Indeed: her lung function increased again! Researchers realized the great value of this discovery. Because it means that lung regeneration is possible in adults.

    So the question is then: How? The consortium is trying to explain this by focusing on recovery processes that take place during adulthood and what changes as we grow older. And also why this repair capacity of the body no longer works in people with COPD. The damage caused by COPD is now irreversible.

    The researchers are examining which communication routes in the lung cells play a role and which growth factors contribute to repair. This fundamental research opens the door to intervention. This results in medicines that can be tested on a laboratory model such as the mini lung. And ultimately in clinical studies for a treatment of currently incurable lung diseases.

  • Sub-project 4: interaction in the lungs

    Cells are just like people. We not only function individually, but also in relation to our environment and in interaction with others. This is exactly how it works with cells.

    The Consortium not only researches how the cells in the lung work, but also explores the environment: what substances are present there and what is the interaction with other cells? Which external factors contribute to maintaining the lung function? And which perhaps contribute to the regeneration or renewal of lung tissue?

    With the knowledge that the researchers gain from this, they can develop medication that stimulates lung repair. These regenerative drugs are tested on an organoid (page 8). Thanks to this innovative mini organ, medicines can be tested without having to do so on individual cells, animals or people. Testing in the lab takes less time and money and can lead to solutions much more quickly and efficiently.

Results

The Consortium has set itself the target of in 2023:

  • To understand fully how lung regeneration works
  • To have an organoid that mimics the functionality of the lung, so that we can test medicines for lung regeneration in a more targeted way.
  • Starting with the first clinical studies of lung stem cells that repair damaged lung tissue