Cell therapy for diabetes using piscine islet tissue

Area of Science:

• Endocrinology
• Xenotransplantation
• Transgenic Technology

Background:

• Islet tissue (Brockmann bodies) in teleost fish is distinct and easily accessible, unlike mammalian pancreatic tissue.
• Tilapia islets demonstrate successful transplantation in diabetic mice, restoring normoglycemia and normal glucose tolerance.
• Tilapia present advantages as xenogeneic donors due to lower costs and reduced xenozoonotic risk.

Purpose of the Study:

• To develop a novel source of insulin for potential therapeutic use in diabetic patients.
• To create transgenic tilapia capable of producing humanized insulin.
• To assess the feasibility of using genetically modified tilapia islets for transplantation.

Main Methods:

• Cloning, sequencing, and site-directed mutagenesis of the tilapia insulin gene to create a humanized version.
• Generation of founder transgenic tilapia carrying the humanized insulin gene construct.
• Demonstration of transgene transmission and expression in offspring beta cells and serum.

Main Results:

• Successful creation of transgenic tilapia with a "humanized" insulin gene.
• Confirmed transmission and expression of the transgene in the first filial (F1) offspring.
• Tilapia islets exhibit glucose responsiveness, high insulin output, cryopreservation potential, and hypoxia resistance.

Conclusions:

• Transgenic tilapia offer a promising source for insulin production and potential islet transplantation.
• Further genomic optimization and characterization of transgenic tilapia are necessary for clinical application.
• Encapsulated tilapia islets could be a viable therapeutic option for type 1 diabetes.