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Improving Functional Architecture of Insulin-Producing Pancreatic Islets

Pancreatic islet transplantation represents a promising treatment for patients with T1D, but a shortage of available healthy islet donors means that there is an insufficient supply of insulin-producing islets to meet the demands for such therapies. Thus, research efforts over the last decade have focused on generating artificial islets from human pluripotent stem cells (hPSCs) as a prospective solution to this scarcity. While these studies have yielded impressive results, current methods are still incapable of producing functional islets that fully recapitulate the activity and glucose responsiveness of normal human islets.

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Improving Functional Architecture of Insulin-Producing Pancreatic Islets

  1. 1. Improving Functional Architecture of Insulin-Producing Pancreatic Islets Dr. Jeffrey D. Serrill City of Hope
  2. 2. 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)
  3. 3. There Are Not Enough Healthy Islet Donors to Meet Current Islet Transplantation Demands for T1D Pancreatic Donor Type 1 Diabetic Patient Islet Isolation Isolated Pancreatic Islets Hepatic Portal Vein Transplant
  4. 4. 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
  5. 5. 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…
  6. 6. 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 δ ε P.P.
  7. 7. 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”
  8. 8. 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 Objective Generation of “Pseudo-Islets” with Therapeutic Potential Against T1D
  9. 9. Thank you! Your generous support brings us a step closer toward eventually bringing an end to Type 1 Diabetes.