Description:
This invention uses a detergent-free decellularized pancreatic extracellular matrix (dpECM) to direct human pluripotent stem cells into self-assembled, vascularized pancreatic islet organoids. By recreating the native pancreatic microenvironment, the technology promotes β-cell maturation, multicellular organization, and glucose-responsive insulin secretion, enabling scalable applications in diabetes therapy, drug screening, and disease modeling.
Background:
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.
Technology Overview:
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.
Advantages:
• 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.
Applications:
• Stem cell–derived islet transplantation therapy for diabetes.
• Bio-artificial pancreas and encapsulated cell therapies.
• Drug discovery and screening for metabolic and endocrine disorders.
• In vitro disease modeling of pancreatic development and diabetes.
• Regenerative medicine applications using tissue-specific ECM scaffolds.
Intellectual Property Summary:
• 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
Stage of Development:
Prototype
Licensing Status:
This technology is available for licensing.
Licensing Potential:
Promising for biotechnology, regenerative medicine, and cell therapy developers seeking scalable, physiologically relevant islet organoids for transplantation, drug screening, and disease modeling.
Additional Information:
Information available upon request.
Inventors:
Sha Jin, Kaiming Ye, Huanjing Bi