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A Safe and Cost-effective Stem Cell Approach for Treating Diabetes

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My research projects focus is on how to generate stem cells and how to convert these stem cells into different types of somatic cells, especially pancreatic beta cells for curing T1D.

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A Safe and Cost-effective Stem Cell Approach for Treating Diabetes

  1. 1. A Safe and Cost-effective Stem Cell Approach for Treating Diabetes Dr. Haisong Liu
  2. 2. Insulin Type I Diabetes (T1D): Pancreatic beta cells fail to produce enough hormone insulin, resulting in elevated levels of glucose in the blood. Pancreatic beta cells produces enough insulin Insulin helps cells to uptake glucose and reduce glucose levels in blood Pancreatic beta cells fail to produce enough insulin More glucose remains in the blood Healthy Pancreas Type I Diabetes Pancreatic islet Pancreatic Beta cells Pancreas Glucose
  3. 3. More than 1.25 million Americans have T1D and suffer from T1D- associated complications Image adapted from PDB101
  4. 4. Conventional treatments for T1D, including insulin injections and islet transplantation, are less than ideal • Insulin injection using a syringe or pump – Frequent blood sugars checks – Risk of hypoglycemia (low blood sugars levels) – Infection at the injection site – difficult to mimic the normal blood sugars produced by a healthy pancreas using this method • Pancreatic islet transplantations Pancreatic islet transplantations more closely mimic the insulin output of a normal pancreas but these cells are scarce, affording the opportunity to very few patients. Pancreatic islets, are clusters of cells scattered throughout the pancreas. Pancreatic islets contain several types of cells, including the beta cells. Pancreatic islet Pancreatic Beta cells Pancreas Image adapted from www.upi.com
  5. 5. Human stem cells multiply infinitely and differentiate into different cell types that can be used in cell replacement therapy, providing hope for curing T1D Pancreatic Beta Cells multiply Stem Cells Neural Cells Liver Cells Skin Cells Blood Cells Kidney Cells
  6. 6. Human stem cells can be converted into functional pancreatic beta cells using a seven-step protocol Functional pancreatic beta cells Human stem cells Intermediate cell stages Human Stem Cells Definitive Endoderm Primitive Gut tube Pancreatic Endoderm Pancreatic Progenitor Endocrine Progenitor Immature Pancreatic Beta cells Functional Pancreatic Beta cells
  7. 7. To use stem cell-derived pancreatic beta cells in the clinic, we first have to overcome the following problems 1. Tumors are frequently observed after transplantation of human stem cell-derived highly-heterozygous cell mixtures 2. the 7 step process currently used is extremely time-consuming and expensive Human Stem Cells Definitive Endoderm Primitive Gut tube Pancreatic Endoderm Pancreatic Progenitor Endoderm Progenitor Immature Pancreatic Beta cells Functional Pancreatic Beta cells
  8. 8. My strategy is to purify and expand the intermediate cells for the generation of pancreatic beta cells in a safe and cost-effective way Expand Expanded Intermediate cells Human Stem Cells Definitive Endoderm Primitive Gut tube Pancreatic Endoderm Pancreatic Progenitor Endocrine Progenitor Immature Pancreatic Beta cells Functional Pancreatic Beta cells Purify
  9. 9. Human Stem Cells Definitive Endoderm Primitive Gut tube Pancreatic Endoderm Pancreatic Progenitor Endocrine Progenitor Immature Pancreatic Beta cells Functional Pancreatic Beta cells 1. My strategy begins with purified pancreatic progenitors or later stage cells, that only generate pancreatic cells, preventing the potential of tumor formation 2. The protocol is reduced from 7 steps to 1-3 steps, enhancing the stability of the cells and greatly reducing time and cost. 3. Making beta cells in bulk is more efficient and suitable for clinical applications Expanded Intermediate cells Differentiation Intermediate cells of 100% purity The advantage of my strategy Expand Purify
  10. 10. I also aim to generate the entire human pancreas by injecting pancreatic intermediate cells into pancreas- deficient rabbit embryos Pancreatic Intermediate cellsSince the experimental rabbit can’t develop a pancreas, the human pancreatic cells may fill the developmental gap and form a human pancreas in the rabbit. Human Stem Cells Definitive Endoderm Primitive Gut tube Pancreatic Endoderm Pancreatic Progenitor Endocrine Progenitor Immature Pancreatic Beta cells Functional Pancreatic Beta cells A rabbit with a human pancreas? Inject pancreatic intermediate cells into pancreas-deficient rabbit embryos
  11. 11. Thank you for your time! Your support is greatly needed and appreciated. Together we can cure Type I Diabetes!

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