An adipose-derived dECM hydrogel as a versatile ECM platform for pancreatic diseases

Pancreatic ductal adenocarcinoma (PDAC) accounts for approximately 90% of pancreatic cancers and remains one of the deadliest malignancies in the worldwide, with a 5-year survival rate of only 8–13%^1–3. PDAC arises from the exocrine compartment (ductal and acinar cells) which acquires pre-neoplastic lesions before progressing to invasive carcinoma^4,5. Obesity and diabetes are major risk factors for PDAC^3,6–8, yet the molecular links between metabolic disorders and pancreatic cancer initiation remain poorly understood.

To address this issue, we aim to develop a physiologically relevant 3D model to investigate how the metabolic microenvironment influences pancreatic cancer development. Our strategy relies on the use of decellularized extracellular matrix (dECM) to better recapitulate key features of the cellular microenvironment. We generated hydrogels from adipose tissue–derived dECM (atdECM), an abundant and easily accessible tissue source compared to pancreatic tissue, with biomechanical properties similar to pancreatic tissue, to support pancreatic cell and organoid culture under defined metabolic conditions, including disease-associated microenvironments.

Proteomic analyses revealed limited batch-to-batch variability in atdECM composition. In parallel, we established and characterized a biobank of pancreatic organoids (PDOs) by RNA-seq analysis. We found that atdECM hydrogels supported healthy and tumor-derived PDOs growth while preserving the exocrine cell phenotype. We are currently developing atdECM derived from patients at risk for PDAC and have already observed structural differences compared to healthy atdECM. This model will be used to investigate the impact of the at-risk microenvironment on both healthy and tumor pancreatic organoids and to identify early PDAC biomarkers. To better mimic the physiopathology of pancreas, pancreatic islets of Langerhans were cultured on atdECM hydrogels and remained viable, with endocrine functionality currently under evaluation. This suggests that atdECM could also support pancreatic endocrine cells, further highlighting the versatility of this biomaterial platform.

Ultimately, this hydrogel system may also offer promising perspectives for regenerative medicine, particularly for applications related to metabolic disorders, as well as providing a versatile platform for personalized medicine and fundamental research.