How inflammation in the lung can impact cell therapy

Today severe lung diseases such as acute respiratory distress syndrome (ARDS) and cystic fibrosis (CF) have no cure. These diseases decrease quality of life and life expectancy for the patients. These patients have to spend a lot of time at the hospital, are not able to work for long periods of time, and their normal daily life is severely affected. Today, the only treatment is lung transplantation. However, there is a shortage of donor lungs, and transplantation comes with severe side effects, so this is not an option for all patients. Therefore, we need to develop new medical options for these patients.

Mesenchymal stromal cells (MSCs) are adult cells that are being tried as a treatment for many severe lung diseases. MSCs are believed to change the immune system in a good way. We do not yet know how this works and how the diseased lung affects the MSC functions and this needs to be further studied.

The aim of this project is to investigate how the MSCs respond to the diseased lung and how the potential for them to be a good treatment changes. If we can understand these interactions, we might be able to improve the medical treatments for patients with ARDS and CF.

We are exposing MSCs to lung samples that have been taken from patients. This mimics the environment that the MSCs will meet when they are given to the patient. By doing this we can see how a certain disease changes the potential for them to be a good treatment. We found that:

• MSCs exposed to samples from patients with ARDS and CF behaved very differently compared to MSCs exposed to samples from healthy people. For example, MSCs exposed to lung samples taken from patients with other lung diseases were better able to alter functions of specific immune cells (macrophages). This did not happen when MSCs were exposed to healthy samples or samples taken from patients with ARDS.

• MSCs exposed to samples from CF patients with Aspergillus (a severe fungal infection in the lungs which is common in CF patients) killed the MSCs. This result was not expected and might explain why they might not work in clinical trials.

These are very exciting and novel findings that could lead the way towards a more efficient MSC-treatment for patients with severe lung disorders.

We believe that MSCs are the future for treating severe lung diseases such as ARDS and CF. However, the success of a good MSC medication lies in understanding how MSCs interact with the lung. We still have a long way to go, but the future looks promising.

Lay summary written by RESPIRE research fellow Sara Rolandsson Enes, PhD