Generation of Glucose-Responsive Stomach Cells for the Treatment of Diabetes

Background & Unmet Need

• 8.4 million patients worldwide have type 1 diabetes
• Standard of care requires lifelong insulin replacement therapy, during which patients remain vulnerable to hypoglycemic episodes
• Islet-cell replacement has shown success as an alternative therapy for diabetes, but is limited by a short supply of donors and transplant rejection
• Generating insulin-producing islet cells from stem cells is a potential solution to patient demand, and could overcome rejection issues if cells are derived from patients
• However, deriving islet cells from iPSCs for autologous cell therapy is complex, and cells are prone to mutation during iPSC reprogramming
• Unmet Need: An abundant and autologous source of insulin-secreting cells as a cell therapy for diabetes

Technology Overview

• The Technology: A method of generating gastric insulin-secreting (GINS) cells from human gastric stem cells (hGSCs) as a transplantable therapeutic for diabetes
• The Discovery: The inventors have developed a novel differentiation path which induces hGSCs to develop β-cell identity
• PoC Data: Cultured hGSCs differentiate into islet-like cells at an efficiency of approximately 70%
• GINS organoids were able to produce insulin upon glucose stimulation 8-10 days after induction
• GINS organoids were stable for the duration of the 6-month period monitored after transplantation
• Transplantation of GINS organoids reversed diabetes in mice and provided glucose homeostasis for over 100 days

Technology Applications

• Manufacture of β-cell transplants from patient biopsies
• Personalized islet-cell replacement therapy for type 1 diabetes and insulin-dependent type 2 diabetes

Technology Advantages

• Gastric stem cells are readily available through biopsy and are easy to propagate
• Applicable to the generation of autologous organoids, reducing risk of rejection
• Transplanted cells did not show proliferation post-transplantation and consequently have low tumorigenic risk