Diabetes mellitus results from the loss or dysfunction of insulin-producing β-cells and affects hundreds of millions worldwide. Current cell replacement therapies are limited by donor islet shortages, immune rejection, and incomplete stem cell differentiation protocols that yield immature, non-functional insulin-producing cells. Existing microenvironments fail to effectively guide stem cells toward physiologically mature, multicellular islet structures capable of glucose-regulated insulin secretion and vascularization. A defined, tissue-specific niche is critically needed to enable robust, scalable production of functional islet organoids for therapeutic and research applications.
The invention employs a detergent-free decellularized pancreatic extracellular matrix (dpECM) to guide human pluripotent stem cells through endocrine lineage differentiation and self-assembly into islet-like organoids. This dpECM gel recreates biochemical cues of the native pancreatic niche and supports spontaneous 3D organization even in 2D culture. The resulting organoids exhibit native-like cellular diversity and expression of insulin, PDX-1, MafA, and C-peptide, with significantly enhanced glucose responsiveness. The dpECM further promotes intra-organoid vascularization by inducing endothelial and pericyte cell formation, improving nutrient exchange and long-term functional stability.
• Tissue-specific dpECM microenvironment promotes natural self-assembly of functional islet organoids.
• Enhanced β-cell maturity with reduced polyhormonal (immature) cell populations.
• Intrinsic induction of vascularization within organoids without co-culture.
• Improved glucose-responsive insulin secretion mimicking native pancreatic islets.
• Detergent-free dpECM preparation preserves critical biochemical cues for differentiation.
• Supports scalable, reproducible generation of transplantable islet organoids.
• Applicable for drug screening, disease modeling, and regenerative medicine.
• United States, 62/479,095, Provisional, 3/30/2017, Converted 1/29/2018
• United States, 15/841,004, Utility, 12/13/2017, Patented 9/8/2020, US 10,767,164; Publication US 2018-0282699 A1
• United States, 17/013,830, Utility, 9/7/2020, Patented 5/21/2024, US 11,987,813; Publication US 2020-0399611 A1
Prototype
This technology is available for licensing.
Promising for biotechnology, regenerative medicine, and cell therapy developers seeking scalable, physiologically relevant islet organoids for transplantation, drug screening, and disease modeling.
Information available upon request.