1. Islet Microencapsulation Presented by: Kristen Galea

2. Outline  Need for Islet microencapsulation  Isolation of Islet cells  Microencapsulation process  Implantation  Cost

3. Where do Islets cells come from?  Pancreas 1 – 1.5 million Islets of Langerhans - 2% of the mass of the pancreas 1 – 1.5 million Islets of Langerhans - 2% of the mass of the pancreas Each Islet contains 2000 – 10000 cells Each Islet contains 2000 – 10000 cells 75% beta cells, 20% alpha cells, D cells and PP cells (or F cells) 75% beta cells, 20% alpha cells, D cells and PP cells (or F cells)

4. Diabetes  Type 1 diabetes – autoimmune disease  Body kills off the Beta cells  Insulin dependant  Insulin shots do not imitate blood glucose levels of non-diabetics  Approximately $600 000 USD in a diabetics lifetime on medication

5. What are the Alternatives?  Pancreas Transplant Invasive surgery Invasive surgery Immunosuppressive drugs required Immunosuppressive drugs required  Islet Transplant Less invasive surgery than transplant Less invasive surgery than transplant Immunosuppressive drugs Immunosuppressive drugs  Microencapsulated Islet Transplant

6. Microencapsulation  Microencapsulation is the process of covering singular cells in a capsule  Important in Diabetes research Eliminates the need for insulin injections Eliminates the need for insulin injections No immunosuppressive drugs are required No immunosuppressive drugs are required

7. Isolating Islet Cells  Must isolate insulin producing cells from pancreas  Requires a pancreas – high demand for organs  Long and delicate procedure Do not want to damage cells in the process Do not want to damage cells in the process

8. Isolation Process  Ricordi Chamber Add Collagenase (an enzyme) to pancreas Add Collagenase (an enzyme) to pancreas Placed in Chamber for digestion phase Placed in Chamber for digestion phase Chamber contains glass beads Chamber contains glass beads Gently agitated Gently agitated Small pieces are filtered Small pieces are filtered Continuous circulation of enzyme through the chamber Continuous circulation of enzyme through the chamber

9. Isolation Process Fresh medium is flushed through system to stop enzymatic reaction Fresh medium is flushed through system to stop enzymatic reaction Islets are purified Islets are purified Tested for viability and purity Tested for viability and purity Sufficient number of cells for transplant Sufficient number of cells for transplant 5000 Islets per kilogram of body weight5000 Islets per kilogram of body weight

10. Materials for Microencapsulation  Biocompatible  Protect cell from immune rejection  Semipermeable membrane Allows insulin and nutrients to pass through Allows insulin and nutrients to pass through  Current research Sodium Alginate – isolated from the seaweed (kelp) Macrocystis pyrifera Sodium Alginate – isolated from the seaweed (kelp) Macrocystis pyrifera Poly L-lysine Poly L-lysine

11. Microencapsulation Process  Mixture of cells and sodium alginate is prepared  Passed through an airjet (or needle)  Droplets formed  Placed in a calcium chloride solution where a gel forms

12. Microencapsulation Process  Gel reacts with Poly L-lysine  Membrane formed around cells  Calcium must be removed from the capsule  Place cells in a Sodium Chloride solution  Semipermeable membrane outside, liquid core

13. Implantation  Implanted into wall of abdominal cavity Blood vessels in cavity bind to capsule Blood vessels in cavity bind to capsule Functions as a new organ Functions as a new organ Nutrients carried into capsule and insulin carried out into blood stream Nutrients carried into capsule and insulin carried out into blood stream  Simple and easy process compared to an organ transplant

14. Cost  Medical grade Sodium Alginate Protanal ® - FMC BioPolymer Protanal ® - FMC BioPolymer  Production of Microencapsulated Islet cells Islet Technology – Minnesota Islet Technology – Minnesota  Estimated cost per transplant: $150 000 - $175 000 USD $150 000 - $175 000 USD

15. Questions