Fibroblast Activation Protein (FAP)-Cleaved Type III Collagen (C3F) is a Potential Marker for Intestinal Fibrosis in Patients with Crohn’s Disease
Introduction
Crohn’s disease (CD) is characterized by chronic inflammation in the gut, where severe complications such as fibrotic strictures require surgical resection. The stricture development involves excessive extracellular matrix (ECM) deposition due to continuous activation of intestinal myofibroblasts, that further contribute to instestinal fibrogenesis. Emerging data suggests that stricture-related intestinal myofibroblasts overexpress a serine protease called fibroblast activation protein (FAP). Furthermore, type III collagen deposition is increased during fibrosis in all layers of the intestinal tract, and studies have shown elevated collagen degradation in serum from patients with CD.
This study aimed to evaluate the potential of FAP-cleaved type III collagen (C3F) as a serum marker for intestinal fibrosis in CD.
C3F is elevated in patients with stenotic CD compared to luminal CD at baseline and remains elevated after surgical resection, suggesting that C3F reflects fibroblast activity during fibrostenosis and tissue remodeling following surgery. In patients with luminal CD, C3F levels were significantly higher, and early C3F levels (baseline, 3 months and 6 months) were significantly positively associated with ileal stenosis assessed at 12 months. This suggests that increased C3F may be predictive of future endoscopic disease activity or even a potential relapse.
Concluding, the findings of this study highlight the potential use of C3F as a novel biomarker for intestinal fibrosis in CD.
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Biomarkers of Extracellular Matrix Remodeling Reflect Pharmacodynamic Effects on IMU-856, an Oral Epigenetic Modulator of Barrier Regeneration
Introduction
Celiac disease (CeD) is characterized by intestinal inflammation and epithelial damage upon exposure to immunogenic gluten peptide, directly disrupting tissue architecture and by extension the extracellular matrix (ECM). The intestinal tissue is rich in ECM proteins such as collagens, which, during inflammation, undergo enzymatic remodeling due to increased proteolytic activity.
IMU-856 is an orally available and systematically acting small-molecule modulator of sirtuin 6 (SIRT6), a histone/non-histone protein deacetylase and transcriptional regulator that aims to restore intestinal barrier function and regenerate bowel epithelium.
This study aimed to investigate biomarkers of ECM remodeling as potential indicators of disease activity and pharmacodynamic response to IMU-856 in patients with CeD.
Biomarkers of ECM remodeling reflect histological inflammation and mucosal architecture parameters, offering a direct insight into intestinal barrier integrity. These biomarkers potentially reflect treatment-induced improvement in intestinal tissue remodeling upon treatment with IMU-856.
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How can a simple blood sample track the progression of Parkinson’s disease?
Parkinson’s disease is a neurological condition that affects the brain and other parts of the nervous system. This animation explores the complex neurodegenerative processes occurring within the brain’s substantia nigra and the groundbreaking role of alpha-synuclein fragments as biomarkers.
Watch this video to learn about the fragmentation of alpha-synuclein, the breakdown of the blood-brain barrier, and how blood-based biomarkers can help identify patients at risk of progression and track treatment response.
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NordicCPa9™, a biomarker of neutrophil activity is associated with transmural healing in pediatric Crohn’s disease
Introduction
CPa9-HNE (nordicCPa9™), a calprotectin fragment released by human neutrophil estate during NETosis, has been shown to strongly correlate with endoscopic disease activity in adults with inflammatory bowel disease (IBD). NordicCPa9™ also serves as an indicator of pharmacodynamic response. This study aimed to investigate the association of nordicCPa9™ with endoscopic disease activity and transmural healing in patients with pediatric CD.
This study showed that nordicCPa9™, a biomarker of neutrophil activity, is associated with mucosal and radiologic mucosal damage in pediatric CD. These findings highlight the potential use of CPa9-HNE as a complementary tool for the endoscopic or radiographic assessment of intestinal mucosal damage/healing and provide an opportunity for further studies in children with CD.
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ECM-derived biomarkers of mucosal damage and neutrophil activity are associated with the failure of VZD
Introduction
Ulcerative colitis (UC) is a chronic relapsing inflammatory disorder affecting the colon. A hallmark of UC is increased immune cell activity and dysregulated extracellular matrix remodeling, particularly of the mucosal collagens type III and IV, leading to mucosal damage. Anti-TNF agents have significantly improved the management of UC-still, up to 40% of patients experience treatment failure, with the anti-α4β7 integrin agent vedolizumab (VDZ) being frequently initiated following anti-TNF failure. This presents the unmet need for biomarkers enabling early assessment of treatment success.
This study investigates whether biomarkers of neutrophil activity, type III, and IV collagen remodeling could serve as early indicators of VDZ failure in anti-TNF experienced patients with UC.
The early increase in CTX-III, reflecting fibrosis resolution, was associated with the absence of VDZ failure, whereas increased neutrophil activity (CPa9-HNE), IAF-mediated collagen type III degradation (C3F) and mucosal damage (C3M, C4M) were associated with the failure of VZD. These findings suggest that biomarkers reflecting neutrophil activity and inflammatory events in the mucosa may serve as promising tools for the early and dynamic assessment of later VDZ treatment outcomes in anti-TNF experienced patients with UC.
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Biomarkers of neutrophil and macrophage activity discriminate non-IBD from CD and associate with endoscopic disease activity
Introduction
Crohn’s disease (CD) is a chronic inflammatory bowel diseases (IBD) characterized by immune cell infiltration and increased proteolytic activity, driving pathological changes in the structure and function of the intestines. Ileocolonoscopy (IC) is the gold standard for diagnosing and monitoring patients with CD but the invasive nature of IC renders it as least acceptable from a patient perspective. Pan-enteric endoscopy (PCE) is an attractive and less invasive method.
This study aimed to investigate whether biomarkers of immune cell activity could identify patients with suspected CD, and if they associated with endoscopic disease activity at IC and PCE.
CPa9-HNE [neutrophil activity] and VICM [macrophage activity] could identify patients with confirmed CD and were associated with endoscopic disease activity. Both biomarkers provided stronger discriminative performance when assessing disease activity by utilizing PCE. Biomarkers of neutrophil and macrophage activity may therefore provide additonal information to endoscopic assessment in the diagnosis and monitoring of CD.
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Markers of extracellular matrix remodeling and wound healing are associated with fibrostenotic Crohn’s disease
Introduction
Crohn’s disease (CD) is a chronic inflammatory condition of the gastrointestinal tract, characterized by excessive extracellular matrix (ECM) remodeling that leads to fibrosis and stricture formation. Strictures are primarily detected using imaging techniques, such as computed tomography and magnetic resonance imaging. However, no validated biomarkers are currently available to assess the presence of strictures. The discovery of such biomarkers would improve early diagnosis and facilitate more effective patient management using anti-fibrotic and anti-inflammatory treatments.
This study aimed to investigate the association of biomarkers reflecting ECM remodeling, fibroblast activity, and neutrophil activity with CD phenotypes.
The fibrosis marker (PRO-C6) was associated with stenosis and was elevated in CD patients with high levels of global stricture scores. Markers of mucosal damage (C7M, C3M/PROC3) and inflammation (CPa9-HNE) were associated with patients with stenosis and penetrating disease and showed a positive association with the global stricture score. These data suggest that markers of ECM remodeling could be valuable tools for assessing fibrostenosis in patients with CD.
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Fibroblast Activity and ECM Turnover: Biomarkers for Outcomes in Fibrosis and Cancer
Watch the replay of this webinar to learn more about why the extracellular matrix (ECM) sits at the center of chronic disease and why fibroblast activity is emerging as a practical, quantifiable lever for prognosis and drug development across fibrosis and oncology.
We highlight key takeaways from over 700 publications, with a focus on the most decision-relevant insights. We also showcase registry data from Denmark documenting that:
4/10 individuals live with ECM changes
1/4 live with fibrosis
55% of deaths are linked to diseases involving ECM remodeling
ECM remodeling is not background biology, but rather a measurable disease process that cuts across organ systems and indications. A substantial share of the population lives with ECM changes, and fibrosis remains a dominant contributor to mortality. This webinar focuses on the practical question: how do we quantify fibroblast-driven matrix turnover in a way that predicts outcomes and can guide therapy development?
Across liver, lung, skin, intestinal, cardiovascular, kidney disease, and across solid tumors, fibroblast activity is repeatedly associated with prognosis. Regulatory momentum also reflects this direction: fibroblast activity biomarkers such as PRO-C3 and PRO-C6 (type III and type VI collagen formation) are supported for prognostic use.
We will connect mechanistic framing (what fibroblasts are doing) with translational readouts (what biomarkers capture in blood), then move into two applied deep dives:
Chronic liver disease: prognostic performance of ECM biomarkers, with emphasis on PRO-C3
Solid tumors: CAF-linked matrix signatures, including collagen type XI, and how baseline fibroblast activity stratifies survival
Dr. Morten Karsdal joined Nordic Bioscience in 2001 and became CEO in June 2010, leading the company to significant advancements in biomarker development and disease biology.
Dr. Karsdal is a KOL in extracellular matrix research, with more than 700 publication, 44,684 citations, and an impressive H-index of 106.
Dr. Karsdal is an honorary professor of inflammation research at the University of Southern Denmark, where he continues to supervise PhD students, fostering the next generation of researchers.
Dr. Karsdal chairs the Extracellular Matrix Pharmacology Congress, an important forum for advancing drug development by focusing on the extracellular matrix (ECM) as a key factor in most chronic diseases. He is renowned for his deep expertise in fibrosis, rheumatology (including rheumatoid arthritis and osteoarthritis), diabetes, and other chronic conditions, particularly in relation to ECM and biomarker research.
Dr. Karsdal has led the development of FDA-approved and supported molecular diagnostics, as well as more than 100 commercialized biomarker assays, including ELISA assays and high precision automated platforms.
He has extensive experience in clinical trial design and the clinical application of biochemical markers, often serving as a consultant to major pharmaceutical companies for the use of serological biomarkers in clinical trials.
In 2016, he and his research team authored the first edition of “Biochemistry of Collagens, Laminins and Elastin,” published by Elsevier Science. The book, now in its 3rd edition as of 2023, is a key resource on collagens and structural proteins, with a focus on their applications in chronic diseases.
Dr. Diana Julie Leeming
Dr. Diana Julie Leeming is the Senior Director of Fibrosis, Hepatic, and Pulmonary Research at Nordic Bioscience.
She joined Nordic Bioscience in 2004 and assumed the role of Director of Fibrosis in 2010, later being promoted to Senior Director in 2024.
Dr. Leeming focuses on developing serologically assessed markers to evaluate extracellular matrix remodeling in patients with pulmonary or hepatic fibrosis, aiding in diagnosis and pharmacodynamic evaluation.
She is a principal inventor of the PRO-C3 assay, a fibrogenesis marker utilized in multiple clinical trial studies.
Dr. Leeming has authored over 280 peer-reviewed publications, demonstrating her extensive contributions to the field.
Her H-index is 69, her I10-index is 195, and her research has garnered over 15,736 citations as of February 2026.
Dr. Nicholas Willumsen
Dr. Nicholas Willumsen is Director of Oncology at Nordic Bioscience, a position he has held since 2022.
He joined Nordic Bioscience in 2012 and became Head of the Oncology Department in 2016.
Dr. Willumsen leads a research group focused on the development of blood-based biomarkers to quantify tumor matrix components in serum from cancer patients.
His work aims to elucidate pharmacodynamic effects, treatment efficacy, and resistance mechanisms across cancer therapies.
The group’s research spans the full translational pipeline, from biomarker discovery to preclinical studies and clinical validation.
A central focus is understanding tumor–extracellular matrix interactions and their role in disease progression and treatment response.
Dr. Willumsen’s research supports the use of non-invasive biomarkers to guide oncology drug development and clinical decision-making.
He has authored peer-reviewed publications with an H-index of 31 and an i10-index of 53.
His work has received 3,246 citations as of February 2026.
This webinar is hosted co-hosted together with the International Society of Extracellular Matrix Pharmacology.
Structural Remodeling, Immune Effects, and Non-Invasive Measurements
Overview
Watch the replay of this webinar to learn more about how cancer-associated fibroblasts (CAFs) and the extracellular matrix (ECM) operate as functional units that shape tumor biology, and how these mechanisms can be translated into clinically useful readouts. This session will cover how circulating ECM fragments can be used as readouts of tumor microenvironment activity, supporting patient stratification, pharmacodynamic monitoring, and hypothesis testing in clinical trials.
Agenda
Welcome and Introduction (Chair) | Dr. Morten Karsdal — 10 min
CAF/ECM Functional Units and Clinical Translation in Human Pancreatic Cancer | Prof.Dr. Edna Cukierman (Fox Chase Cancer Center) — 20 min
Copper Depletion, ECM/Collagen Remodeling, and Immune Response in Breast Cancer | Prof. Dr. Linda T. Vahdat (Dartmouth Hitchcock Medical Center) — 20 min
Non-Invasive ECM-Derived Biomarkers of CAF and Immune Cell Activity in Clinical Cancer Research | Dr. Nicholas Willumsen (Nordic Bioscience) — 20 min
CAFs and the ECM do not act as background structure in tumors: they form interacting, measurable functional units that influence tissue mechanics, signaling, and immune context. In pancreatic cancer, these CAF/ECM units are central to how tumors organize their local environment, including ECM deposition and remodeling patterns that can affect therapeutic response and disease behavior, where immune regulation also plays a part of this unit-level biology.
In breast cancer, ECM remodeling, particularly collagen turnover and reorganization, links directly to immune activity and tumor progression. A clinically relevant question is which upstream levers shift ECM remodeling in ways that also alter immune response. This webinar includes insights into how copper depletion can influence collagen remodeling and immune dynamics, with implications for how ECM state may be modified and monitored in patients.
Finally, translation requires measurement. Non-invasive ECM-derived biomarkers offer a practical route to quantify CAF activity and immune cell-associated processes in clinical research. The session covers how circulating ECM fragments can be used as readouts of tumor microenvironment activity, supporting patient stratification, pharmacodynamic monitoring, and hypothesis testing in clinical trials.
Prof. Dr. Linda T. Vahdat is Section Chief of Medical Oncology and Interim Section Chief of Hematology at Dartmouth Hitchcock Medical Center, and Professor of Medicine at the Geisel School of Medicine at Dartmouth.
She is a board-certified medical oncologist specializing in breast cancer, with a particular focus on metastatic and triple-negative breast cancer.
Prof. Dr. Vahdat’s clinical and research mission centers on preventing metastasis and improving survival and quality of life through individualized, research-guided cancer care.
Her approach emphasizes tailoring therapy intensity to disease stage, aiming for cure with minimal long-term toxicity in early disease and optimal longevity and well-being in metastatic settings.
She integrates translational research into clinical practice, including investigations into copper biology and its role in cancer progression and metastasis.
Prof. Dr. Vahdat joined Dartmouth Cancer Center in 2022 and plays a key leadership role in the Comprehensive Breast Program.
She earned her MD from Mount Sinai School of Medicine, completed residency training at Mount Sinai Hospital, and a Hematology/Oncology fellowship at Memorial Sloan Kettering Cancer Center.
She also holds an MBA from the MIT Sloan School of Management, reflecting expertise in healthcare leadership and strategy.
Prof. Dr. Vahdat is committed to patient-centered oncology, prioritizing shared decision-making, education, and empowerment throughout the cancer journey.
Her work aligns clinical excellence with translational insight to advance outcomes in breast cancer and metastatic disease.
Prof. Dr. Edna Cukierman
Prof. Dr. Edna Cukierman is the Marvin & Concetta Greenberg Chair in Pancreatic Cancer Research and ACS Wilmott Family Professor of Pancreatic Cancer at Fox Chase Cancer Center.
She is Co-Leader of the Cancer Signaling and Microenvironment Program and Director of the Spatial Immuno-Proteomic Initiative, specializing in high-plex spatial immunofluorescence.
Her research centers on the desmoplastic tumor microenvironment (TME) and how cancer-associated fibroblasts (CAFs) and CAF-generated extracellular matrix (ECM) regulate tumor progression.
Prof. Dr. Cukierman’s laboratory pioneered a unique 3D culture system that mimics in vivo mesenchymal stroma to study functional tumor–stroma interactions.
She developed Harmonic Output of Stromal Traits (HOST) and the HOST-Factor, a quantitative framework to define functional states of TME cells.
Her work dissects how CAF–ECM units interact with immune cells, nerves, and cancer cells to drive tumor-supportive or tumor-suppressive behaviors.
A key focus is evaluating HOST-Factor values as TME-based prognostic biomarkers and predictors of therapeutic response.
Prof. Dr. Cukierman integrates high-plex spatial immunofluorescence with AI-guided image analysis to generate cell-resolved TME functional maps.
She has received numerous honors, including AACR TME Working Group Chair (2024–2026), multiple pancreatic cancer foundation awards, and election to leadership roles in the American Society of Matrix Biology.
Her work aims to enable next-generation ECM- and TME-targeted therapies, directly aligning with translational goals in pancreatic cancer research.
Dr. Nicholas Willumsen
Dr. Nicholas Willumsen is Director of Oncology at Nordic Bioscience, a position he has held since 2022.
He joined Nordic Bioscience in 2012 and became Head of the Oncology Department in 2016.
Dr. Willumsen leads a research group focused on the development of blood-based biomarkers to quantify tumor matrix components in serum from cancer patients.
His work aims to elucidate pharmacodynamic effects, treatment efficacy, and resistance mechanisms across cancer therapies.
The group’s research spans the full translational pipeline, from biomarker discovery to preclinical studies and clinical validation.
A central focus is understanding tumor–extracellular matrix interactions and their role in disease progression and treatment response.
Dr. Willumsen’s research supports the use of non-invasive biomarkers to guide oncology drug development and clinical decision-making.
He has authored peer-reviewed publications with an H-index of 30 and an i10-index of 59.
His work has received 2,824 citations as of June 2025.
This webinar is hosted co-hosted together with the International Society of Extracellular Matrix Pharmacology.
At Nordic Bioscience, we provide central and specialty lab services that encompass a broad range of diagnostic and exploratory tests such as the ELF™ (Enhanced Liver Fibrosis) test.
What is the ELF™ Test?
The ELF™ test is available on our high-throughput Siemens Atellica IM® platform, where it brings together three direct extracellular-matrix biomarkers into a validated composite score: HA, PIIINP, and TIMP-1.
The analytes are automatically measured, and the software calculates and reports a unitless numeric score. Increasing ELF scores are linked to both biopsy-proven fibrosis and prognosis for clinically significant outcomes.
The ELF scoring system– Severityassessment (against biopsy-proven fibrosis)
None to Mild
Score: <7.7
Moderate
Score: ≥7.7 to <9.8
Severe
Score: ≥9.8 (associated with high risk of significant fibrosis)
Cirrhosis
Score: ≥11.3*
These insights help clinicians and researchers to assess fibrosis severity and stratify risk in metabolic and chronic liver diseases, including MASLD/NAFLD.
Why measure with us?
Efficient sample requirements – We require just 165 µL of serum, reducing patient burden and supporting streamlined sampling in both clinical practice and study settings.
Excellent long-term sample stability – Samples are stable for up to 25 months at ≤ –70°C (in-house data) and up to 3 years according to published literature which is ideal for global trials and multi-site studies
Integrated biomarker strategy – ELF is complemented by nordicPRO-C3™, our collagen formation biomarker that reflects active fibrogenesis, offering a dual perspective.
This creates a more complete fibrosis profile than traditional liver enzymes alone (ASAT, ALAT), enabling more confident interpretation and decision-making.
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