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Research at CPC-M - When organs stick together after surgery

Research at CPC-M

When organs stick together after surgery

How does the protective lining of the internal organs, the mesothelium, recover after surgery-related damage?

Mesothelium, schematic drawing
© Yuval Rinkevich
Mesothelium, schematic drawing

The mesothelium is a cell layer that lines the chest and abdominal cavity and surrounds organs such as the lungs, heart, liver or reproductive organs. It can be described as the protective clothing of the organs because it plays an important role in immune responses and wound-healing processes. It also harbors precursors for a variety of necessary cell types such as fibroblasts or muscle cells. However, the mesothelium may also be at the center of a harmful process that often occurs after surgery in the abdomen and chest:

Organs that are normally not connected begin to stick together and grow together. These adhesions can have severe consequences for the patient: chronic pain, infertility, deterioration of the quality of life or even death. The National Institutes of Health in the USA estimate that about 90% of patients develop adhesions after abdominal surgery. Of these, about 20% develop further adhesion-related complications. However, not much is yet known about the exact processes of these postoperative adhesions. 

Searching for the trigger – what happens when organs stick together?

Abdominal adhesion
© Yuval Rinkevich
Abdominal adhesion

What scientists know about adhesions is that these begin with a surgery-induced injury of the cell layer surrounding the internal organs. The injury leads to hypoxia, an oxygen deficiency that in turn triggers inflammation. This ultimately leads to an unwanted coagulation cascade: The cells form fibrin bridges between adjacent surfaces – the organs stick together like a net. But what is the primary molecular trigger, what are the original cells for this development? 

The hypothesis of the team is:

The development of postoperative adhesions is coordinated by the injured mesothelial cells. Using clone analysis and lineage tracking, the team was able to identify these cells as progenitor cells. Primary adhesion triggers are two proteins increasingly produced by these cells, podoplanin (PDPN) and mesothelin (MSLN). 

Further insights: The transcription factor HIF1α is an important regulator in the development of adhesions, in particular it regulates the degree of severity. This hypothesis is supported by a comparison between different adhesion severities. In addition, the team assumes that the formation of adhesion leads to the release of messenger substances in the blood that can serve as potential biomarkers.

The objective: Therapeutic measures to prevent the organs from sticking together

Abdominal adhesion, close-up
© Yuval Rinkevich
Abdominal adhesion, close-up

After years of research, the team has identified possible therapies:

  • Targeted anti-mesothelin antibody-mediated immunotherapy reduces preformed adhesions. The combination of anti-MSLN and anti-CD47 (leukocyte surface antigen) is even more effective.  
  • Inhibition of the transcription factor HIF1α substantially improves the injury program in damaged mesothelial cells and reduces the severity of the adhesion.

In the future, a project is planned in cooperation with a surgical clinic. Postoperative adhesions will be analyzed in order to identify new marker proteins.

Head of Group

[Translate to Englisch:] Porträt Dr. Yuval Rinkevich

Dr. Yuval Rinkevich

Assistant:

Sandra Schiener
Tel.: +49-89-3187-43060
Mail: sandra.schiener (at) helmholtz-muenchen.de

Helmholtz Zentrum München
Institute of Lung Biology and Disease
Max-Lebsche-Platz 31
81377 München

Team:

Dr. Juliane Wannemacher, Labmanager
Vijay Rajendran, PhD Student
Simon Christ, PhD Student
Pushkar Ramesh, PhD Student
Shruthi Kalgudde Gopal, PhD Student
Dr. Martin Mück Häusl, Senior Postdoc
Dr. Adrian Fischer, Postdoc
Aydan Sardogan, PhD Student
Dr. Dongsheng Jiang, Postdoctoral fellow
Young Hwa Kim, Postdoctoral fellow
Tankut Gokhan Güney, Postdoctoral fellow
Shaohua Zhu, PhD Student
Yuchen Zhu, PhD Student
Haifeng Ye, PhD Student
Donovan Gallegos Correa, PhD Student
Qing Yu, PhD Student
Li Wan, PhD Student
Ruoxuan Dai, PhD Student
Robert Kopplin, BSc Student

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