Improving Functional Architecture of Insulin-Producing Pancreatic

Islets

Dr. Jeffrey D. SerrillCity of Hope

Patients with Type 1 Diabetes (T1D) Cannot Adequately Secrete Insulin in the Presence

of Blood Glucose

Blood Glucose

Type 1 Diabetic IsletsNormal Pancreatic Islets

No Insulin Production(Blood Glucose Levels Remain High)

Adequate Insulin Production(Blood Glucose Levels Decrease)

There Are Not Enough Healthy Islet Donors to Meet Current Islet Transplantation

Demands for T1DPancreatic Donor Type 1 Diabetic Patient

Islet Isolation

Isolated Pancreatic Islets

Hepatic Portal Vein Transplant

Generating Pancreatic Islets from Pluripotent Stem Cells is a Promising

Method For Addressing This Shortage

Pluripotent Stem Cells

Small Molecule Treatment

Pancreatic Progenitor Cells

Small Molecule Treatment

Mature Pancreatic Islet

Cells

Transplantation for Future T1D

Treatments

Different Types of Endocrine Cells in the Pancreatic Islet Communicate to Improve

Functionality

Beta cells express insulin

Alpha cells express glucagon

Delta cells express somatostatin

Epsilon cells express somatostatin

P.P. cells express Pancreatic Polypeptide

In Isolation, Individual Endocrine Subtypes Lack Functionality

In Combination, Individual Endocrine Cells Collaborate to Produce a Functional Islet

However, the Exact Nature with Which these Cells Interact is Still Not Well Understood…

My Project Aims to Utilize a Novel Molecular Tool to Generate Purified Pools of Each

Endocrine Cell Type….

Pluripotent Stem Cells

Small Molecule Treatment

Pancreatic Progenitor Cells

Novel Molecular Tool

α

β

δε

P.P.

And Then Combine These Pools to Form Functional “Pseudo-Islets” Using a Novel

Aggregation Platform

Endocrine Single-Cell Suspensions “Pseudo-Islet” Generation in Novel

Agarose Microwell Platform

Functional, Optimized

“Pseudo-Islets”

Functional, Optimized

“Pseudo-Islets”

Analysis of “Pseudo-Islet” Functionality Will Allow us to Determine the Optimal

Conditions for Producing Functional Islets from Pluripotent Stem Cells

Optimal Ratios of Endocrine Subtypes

Optimal Size for Therapeutic Islets

Functionality Assessments

Analysis of Intercellular Communication

Gene Expression Studies

Adequate Hormone Expression

Overall ObjectiveGeneration of

“Pseudo-Islets” withTherapeutic Potential

Against T1D

Thank you! Your generous support brings us a step closer

toward eventually bringing an end to Type 1 Diabetes.