Advances in Extracellular Matrix-Associated Diagnostics and Therapeutics

Morten Karsdal¹, Thomas R Cox^{2

3}, Amelia L Parker^{2

3}, Nicholas Willumsen¹, Jannie Marie Bülow Sand¹, Gisli Jenkins⁴, Henrik H Hansen⁵, Anouk Oldenburger⁶, Kerstin E Geillinger-Kaestle⁷, Anna Thorsø Larsen¹, Darcey Black⁸, Federica Genovese¹, Alexander Eckersley⁹, Andrea Heinz¹⁰, Alexander Nyström¹¹, Signe Holm Nielsen¹, Lucas Bennink¹², Lars Johannsson¹³, Anne-Christine Bay-Jensen¹, Dana E Orange¹⁴, Scott Friedman¹⁵, Mads Røpke¹⁶, Vincent Fiore¹⁷, Detlef Schuppan¹⁸, Florian Rieder¹⁹, Benjamin Simona²⁰, Lee Borthwick^{21

22}, Mark Skarsfeldt¹, Haakan Wennbo²³, Paresh Thakker²³, Ruedi Stoffel²⁴, Graham W Clarke^{25

26}, Raghu Kalluri²⁷, Darren Ruane²⁸, Faiez Zannad²⁹, Joachim Høg Mortensen¹, Dovile Sinkeviciute¹, Fred Sundberg³⁰, Molly Coseno³⁰, Christian Thudium¹, Adam P Croft^{31

32}, Dinesh Khanna³³, Michael Cooreman³⁴, Andre Broermann³⁵, Diana Julie Leeming¹, Ali Mobasheri^{36

37

38

39}, Sylvie Ricard-Blum⁴⁰

Affiliations

¹ Nordic Bioscience, 2730 Herlev, Denmark.
² Garvan Institute of Medical Research, Sydney 2010, Australia.
³ School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW, Sydney 2010, Australia.
⁴ Margaret Turner Warwick Centre for Fibrosing Lung Disease, National Heart and Lung Institute, NIHR Imperial Biomedical Research Centre, Imperial College London, London SW7 2AZ, UK.
⁵ Gubra, 2970 Hørsholm, Denmark.
⁶ Global Drug Discovery, Novo Nordisk, 2760 Maaloev, Denmark.
⁷ Department of Immunology and Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, 88400 Biberach an der Riss, Germany.
⁸ TherapeutAix UG, 52062 Aachen, Germany.
⁹ Wellcome Centre for Cell Matrix Research, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, University of Manchester, Manchester M13 9PL, UK.
¹⁰ LEO Foundation Center for Cutaneous Drug Delivery, Department of Pharmacy, University of Copenhagen, 2100 Copenhagen, Denmark.
¹¹ Department of Dermatology, Faculty of Medicine, Medical Center-University of Freiburg, 79106 Breisgau, Germany.
¹² 3Helix, Inc., Salt Lake City, UT 84101, USA.
¹³ Antaros Medical AB, 752 37 Uppsala, Sweden.
¹⁴ Hospital for Special Surgery, The Rockefeller University, New York, NY 10065, USA.
¹⁵ Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
¹⁶ Novo Nordisk, 2860 Søborg, Denmark.
¹⁷ Boehringer Ingelheim, 55218 Ingelheim am Rhein, Germany.
¹⁸ Institute of Translational Immunology, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
¹⁹ Department of Inflammation and Immunity, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
²⁰ Ectica Technologies AG, 8005 Zürich, Switzerland.
²¹ FibroFind Ltd., FibroFind Laboratories, Medical School, Newcastle upon Tyne NE2 4HH, UK.
²² Newcastle Fibrosis Research Group, Biosciences Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.
²³ Takeda, Translational Medicine Biomarkers Gastrointestinal & Global, Boston, MA 02110, USA.
²⁴ Roche Diagnostics International Ltd., 6343 Rotkreuz, Switzerland.
²⁵ Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, 431 83 Gothenburg, Sweden.
²⁶ School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College, London E1 9RT, UK.
²⁷ Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
²⁸ Janssen Immunology, Translational Sciences and Medicine, La Jolla, CA 92037, USA.
²⁹ Division of Heart Failure and Hypertension, and of the Inserm CIC, University of Lorraine, 54000 Metz, France.
³⁰ Sengenics Corporation LLC, Wilmington, DE 19801, USA.
³¹ National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre, University of Birmingham, Birmingham B15 2TT, UK.
³² Institute of Inflammation and Ageing, Queen Elizabeth Hospital, University of Birmingham, Birmingham B15 2TT, UK.
³³ Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
³⁴ Inventiva Inc., New York, NY 10001, USA.
³⁵ Department of CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, 88400 Biberach an der Riss, Germany.
³⁶ Faculty of Medicine, University of Oulu, 90570 Oulu, Finland.
³⁷ Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, 08406 Vilnius, Lithuania.
³⁸ Faculté de Médecine, Université de Liège, 4000 Liège, Belgium.
³⁹ Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
⁴⁰ Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), UMR 5246 CNRS, ICBMS, University Lyon 1, 69622 Villeurbanne Cedex, France.

PMID: 40142664
PMCID: PMC11943371
DOI: 10.3390/jcm14061856

Review

Advances in Extracellular Matrix-Associated Diagnostics and Therapeutics

Morten Karsdal et al. J Clin Med. 2025.

. 2025 Mar 10;14(6):1856.

doi: 10.3390/jcm14061856.

Authors

Affiliations

¹ Nordic Bioscience, 2730 Herlev, Denmark.
² Garvan Institute of Medical Research, Sydney 2010, Australia.
³ School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW, Sydney 2010, Australia.
⁴ Margaret Turner Warwick Centre for Fibrosing Lung Disease, National Heart and Lung Institute, NIHR Imperial Biomedical Research Centre, Imperial College London, London SW7 2AZ, UK.
⁵ Gubra, 2970 Hørsholm, Denmark.
⁶ Global Drug Discovery, Novo Nordisk, 2760 Maaloev, Denmark.
⁷ Department of Immunology and Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, 88400 Biberach an der Riss, Germany.
⁸ TherapeutAix UG, 52062 Aachen, Germany.
⁹ Wellcome Centre for Cell Matrix Research, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, University of Manchester, Manchester M13 9PL, UK.
¹⁰ LEO Foundation Center for Cutaneous Drug Delivery, Department of Pharmacy, University of Copenhagen, 2100 Copenhagen, Denmark.
¹¹ Department of Dermatology, Faculty of Medicine, Medical Center-University of Freiburg, 79106 Breisgau, Germany.
¹² 3Helix, Inc., Salt Lake City, UT 84101, USA.
¹³ Antaros Medical AB, 752 37 Uppsala, Sweden.
¹⁴ Hospital for Special Surgery, The Rockefeller University, New York, NY 10065, USA.
¹⁵ Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
¹⁶ Novo Nordisk, 2860 Søborg, Denmark.
¹⁷ Boehringer Ingelheim, 55218 Ingelheim am Rhein, Germany.
¹⁸ Institute of Translational Immunology, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
¹⁹ Department of Inflammation and Immunity, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
²⁰ Ectica Technologies AG, 8005 Zürich, Switzerland.
²¹ FibroFind Ltd., FibroFind Laboratories, Medical School, Newcastle upon Tyne NE2 4HH, UK.
²² Newcastle Fibrosis Research Group, Biosciences Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.
²³ Takeda, Translational Medicine Biomarkers Gastrointestinal & Global, Boston, MA 02110, USA.
²⁴ Roche Diagnostics International Ltd., 6343 Rotkreuz, Switzerland.
²⁵ Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, 431 83 Gothenburg, Sweden.
²⁶ School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College, London E1 9RT, UK.
²⁷ Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
²⁸ Janssen Immunology, Translational Sciences and Medicine, La Jolla, CA 92037, USA.
²⁹ Division of Heart Failure and Hypertension, and of the Inserm CIC, University of Lorraine, 54000 Metz, France.
³⁰ Sengenics Corporation LLC, Wilmington, DE 19801, USA.
³¹ National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre, University of Birmingham, Birmingham B15 2TT, UK.
³² Institute of Inflammation and Ageing, Queen Elizabeth Hospital, University of Birmingham, Birmingham B15 2TT, UK.
³³ Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
³⁴ Inventiva Inc., New York, NY 10001, USA.
³⁵ Department of CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, 88400 Biberach an der Riss, Germany.
³⁶ Faculty of Medicine, University of Oulu, 90570 Oulu, Finland.
³⁷ Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, 08406 Vilnius, Lithuania.
³⁸ Faculté de Médecine, Université de Liège, 4000 Liège, Belgium.
³⁹ Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
⁴⁰ Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), UMR 5246 CNRS, ICBMS, University Lyon 1, 69622 Villeurbanne Cedex, France.

PMID: 40142664
PMCID: PMC11943371
DOI: 10.3390/jcm14061856

Abstract

The extracellular matrix (ECM) is the common denominator of more than 50 chronic diseases. Some of these chronic pathologies lead to enhanced tissue formation and deposition, whereas others are associated with increased tissue degradation, and some exhibit a combination of both, leading to severe tissue alterations. To develop effective therapies for diseases affecting the lung, liver, kidney, skin, intestine, musculoskeletal system, heart, and solid tumors, we need to modulate the ECM's composition to restore its organization and function. Across diverse organ diseases, there are common denominators and distinguishing factors in this fibroinflammatory axis, which may be used to foster new insights into drug development across disease indications. The 2nd Extracellular Matrix Pharmacology Congress took place in Copenhagen, Denmark, from 17 to 19 June 2024 and was hosted by the International Society of Extracellular Matrix Pharmacology. The event was attended by 450 participants from 35 countries, among whom were prominent scientists who brought together state-of-the-art research on organ diseases and asked important questions to facilitate drug development. We highlight key aspects of the ECM in the liver, kidney, skin, intestine, musculoskeletal system, lungs, and solid tumors to advance our understanding of the ECM and its central targets in drug development. We also highlight key advances in the tools and technology that enable this drug development, thereby supporting the ECM.

Keywords: chronic diseases; drug development; extracellular matrix; liver disease; pharmacology congress; solid tumors.

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Conflict of interest statement

Authors M.K., N.W., J.M.B.S., A.-C.B.-J., M.S., J.H.M., D.S., C.T., D.J.L., A.T.L., F.G., S.H.N. are from Nordic Bioscience. H.H.H. is from Gubra. A.O. and M.R. are from Novo Nordisk. K.E.G.-K. and A.B. are from Boehringer Ingelheim Pharma GmbH & Co. KG. D.B. is from TherapeutAix UG. L.B. (Lucas Bennink) is from 3Helix, Inc. L.J. is from Antaros Medical AB. V.F. is from Boehringer Ingelheim. D.R. is from Janssen. B.S. is from Ectica Technologies AG. L.B. (Lee Borthwick) is from FibroFind Ltd. H.W. and P.T. are from Takeda. R.S. is from Roche Diagnostics International Ltd. F.S. and M.C. (Molly Coseno) are from Sengenics Corporation LLC. M.C. (Michael Cooreman) is from Inventiva Inc. All industry partners, except Nordic Bioscience, are not discussing their own products but exclusively addressing pre-competitive biomarkers. All contributors from Nordic Bioscience are full-time employees of the company, hold stock, and are dedicated to the discovery, development, and commercialization of biomarkers.

Figures

**Figure 1**
Interactions between the ECM and immune cells are the key drivers behind inflammatory response, regular tissue repair, and fibrosis development mechanisms. Modified from Zawadzki et al. [5].

**Figure 2**
ECM remodeling is fundamental across chronic, usually fibrodegenerative, fibroinflammatory diseases. More than 50 different diseases have ECM remodeling as a common denominator. Modified from [160] with permission.

See this image and copyright information in PMC

References

1. Karsdal M.A., Detlefsen S., Daniels S.J., Nielsen M.J., Krag A., Schuppan D. Is the Total Amount as Important as Localization and Type of Collagen in Liver Fibrosis Attributable to Steatohepatitis? Hepatology. 2019;71:346–351. doi: 10.1002/hep.30969. - DOI - PubMed
1. Karsdal M.A., Kraus V.B., Shevell D., Bay-Jensen A.C., Schattenberg J., Surabattula R.R., Schuppan D. Profiling and targeting connective tissue remodeling in autoimmunity—A novel paradigm for diagnosing and treating chronic diseases. Autoimmun. Rev. 2020;20:102706. doi: 10.1016/j.autrev.2020.102706. - DOI - PubMed
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1. Karsdal M.A., Daniels S.J., Nielsen S.H., Bager C., Rasmussen D.G.K., Loomba R., Surabattula R., Villesen I.F., Luo Y., Shevell D., et al. Collagen biology and non-invasive biomarkers of liver fibrosis. Liver Int. 2020;40:736–750. doi: 10.1111/liv.14390. - DOI - PubMed
1. Zawadzki A., Leeming D.J., Sanyal A.J., Anstee Q.M., Schattenberg J.M., Friedman S.L., Schuppan S.D., Karsdal M.A. Hot and Cold Fibrosis: The Role of Serum Biomarkers to Assess the Immune Mechanisms and ECM-Cell Interactions in Human Fibrosis. J. Hepatol. 2025. in press . - PubMed

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Advances in Extracellular Matrix-Associated Diagnostics and Therapeutics

Affiliations

Advances in Extracellular Matrix-Associated Diagnostics and Therapeutics

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

LinkOut - more resources

Full Text Sources