ECM2026, 14-17 June 2026, Copenhagen, DenmarkA pan-matrisome tissue atlas of fibrosis and solid tumors to decode ECM composition and biology
Giuseppe Mazza, Co-founder and CEO, Engitix
Abstract: Systemic
Breaking down the matrix: the interplay between fibrosis, inflammation, and autoimmunity in systemic sclerosis
Dinesh Khanna, Professor at the Department of Internal Medicine, University of Michigan.
Abstract: SIntroduction. Excessive ECM accumulation is the common denominator to multiple chronic conditions and is a primary cause of mortality worldwide. Despite its importance, the ECM remains an overlooked area in drug discovery. A deep understanding of changes in ECM composition in disease may uncover opportunities for novel therapeutic approaches. Our aim was to establish an end-to-end platform to decode the composition and biology of ECM. By linking tissue collection for both healthy and diseased individuals to bespoke, tissue-specific decellularization protocols developed alongside robust quality control panels, we enabled in-depth profiling of their protein composition. The resulting ECMs can be used for multiple applications, spanning target identification, generation of assays to study the ECM lifecycle, and biomarker discovery.
Methods. We have generated a comprehensive library of human decellularized ECMs derived from multiple fibrotic and solid tumor tissues of the GI and hepatopancreatic systems, including steatotic and cholestatic liver disease (ALD, MASH, PSC), fibrostenotic Crohn’s disease, pancreatic ductal adenocarcinomas, primary and metastatic colorectal cancer, and hepatocellular carcinomas. ECM composition has been assessed by multiple state-of-the-art proteomics techniques (DDA-TMT and DIA-LFQ), paired with an AI-enhanced processing pipeline to improve protein identification. The resulting matrisomes from different indications were integrated for cross-disease comparisons. Differential protein abundance between disease and control groups was determined for each indication using the limma framework with robust fitting. Upregulated ECM proteins were subsequently subjected to overrepresentation analysis against Reactome and GO Biological Process gene sets, and shared and indication-specific enriched pathways were compared across indications.
Results. We demonstrate that ECM samples from different fibrotic donors and indications cluster according to disease group regardless of decellularization protocol and proteomics method used. Further, the resulting pan-fibrotic matrisome analysis reveals the presence of shared core fibrotic pathways and tissue-specific signatures. In fibrotic liver, proteins upregulated in the matrisome mapped into the spatial context using single-cell and spatial transcriptomics reveals predominant localization to septal stromal populations. Similarly, the assessment of ECM composition across solid tumors from different donors and indications indicated that clustering is primarily driven by the disease group, rather than the methodologies used. Further, desmoplastic tumors are characterized by the presence of shared core ECM pathways.
Conclusions. The generated ECM atlas across fibrotic and neoplastic conditions is independent from the methodologies utilized and accurately reflects donor- and indication- specific differences. The enhanced understanding of core and specific pathways modulated in disease may guide the development of improved and novel therapeutic strategies.
Therapeutic potential of fibroblasts for the treatment of chronic diseases
Hamid Khoja, , Chief scientific officer, FibroBiologics
Abstract: Human dermal fibroblasts (HDFs), one of the most abundant cells in the human body, are remarkable for their stem cell-like properties. They exhibit pluripotency, enabling differentiation into diverse cell types, including chondrocytes, hepatocytes, cardiomyocytes, and mesenchymal stem cells. Importantly, certain HDF subtypes are potent immune modulators, secreting cytokines that can restore immune homeostasis. HDFs play a critical and dynamic role at every stage of the wound-healing process, underscoring their immense therapeutic promise.
Since stem cells have yet to demonstrate full clinical potential due to spontaneous differentiation, expensive growth media requirements, and difficulty in scaling production for clinical use, fibroblasts are an excellent already-differentiated alternative cell source with simple media requirements and potentially unlimited scale-up potential.
In this presentation, we will present our pipeline of HDF-based potential therapeutics that reflect fibroblast characteristics. We will share both IND-enabling preclinical data and, potentially, 6-week interim clinical data from our phase I/II clinical trial for the treatment of diabetic foot ulcers (DFUs). Furthermore, we will present our preclinical data on the treatment of psoriasis and multiple sclerosis, highlighting the therapeutic potential of DHFs in these two highly prevalent autoimmune disorders. In addition, we will share data from our early-phase projects focusing on the development of a fibroblast-based thymic organoid to restore lost thymic function due to age-related thymic involution, and a fibroblast-based pancreatic organoid in which fibroblasts protect fragile pancreatic cells and secrete insulin upon glucose stimulation.
