Improving Functional Architecture of Insulin-Producing Pancreatic Islets
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Transcript of Improving Functional Architecture of Insulin-Producing Pancreatic Islets
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Improving Functional Architecture of Insulin-Producing Pancreatic
Islets
Dr. Jeffrey D. SerrillCity of Hope
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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)
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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
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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
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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…
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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.
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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”
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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
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Thank you! Your generous support brings us a step closer
toward eventually bringing an end to Type 1 Diabetes.