1. Stem cell technologies Current state Future promise Where UCI fits in to the Post Prop. 71 world of biotechnology development in California

2. Proposition 71: Purpose and Intent Create California Institute for Regenerative Medicine.  Oversight by Independent Citizen’s Oversight Committee (ICOC). Support the development of technologies involving pluripotent stem cell and progenitor cell.  Prohibit human reproductive cloning

3. Proposition 71: Funds Funding details  Authorizes an average of $295 million per year in bonds over a 10-year period, $3 billion total  In any year, no more than $350 million in bonds to be issued  If less than $350 million is issued in any year, the remaining permitted amount may be carried over to one or more subsequent years

4. Proposition 71: Research facilities Research facilities that can be used for research on “non-approved lines” are a priority. Accordingly, up to 10% of the funds will be used to build scientific and medical research facilities of nonprofit entities. These are to be constructed in the first five years, with priority given to facilities that can be brought on line within the first 2 years. Funding through Prop. 71 for development of facilities requires a 20% match.

5. Proposition 71: Oversight The ICOC must meet in an open meeting format. Closed sessions may be conducted when discussing: Matters involving information relating to patients or medical subjects. Matters involving confidential intellectual property or work product Matters involving prepublication, confidential scientific research or data Matters concerning the appointment, employment, performance, compensation, or dismissal of institute officers and employees

6. Proposition 71: Scientific and Medical Working Groups Scientific and Medical Research Funding Working Group. Scientific and Medical Accountability Standards Working Group. Scientific and Medical Research Facilities Working Group.

7. Blastocyst - from In Vitro Fertilization Clinic Inner Cell Mass (Stem Cells) “Blueprint” cells A primer on Human Embryonic Stem Cells A Blastocyst is a hollow ball of cells with a small clump of stem cells inside RR C

8. “Blueprint” cells Human Embryonic Stem Cells Pipette Stem Cells To remove the stem cells, the Blastocyst is opened and the stem cells removed with a pipette Blastocyst - from In Vitro Fertilization Clinic Stem Cells “Blueprint” cells A Blastocyst is a hollow ball of cells with a small clump of stem cells inside

9. Pipette Stem Cells Petri Dish Human Embryonic Stem Cells To remove the stem cells, the Blastocyst is broken open and the stem cells removed with a pipette(an ultra thin glass tube) The stem cells are placed in a dish and are fed and cared for (each blastocyst = 1 stem cell line) Blastocyst - from In Vitro Fertilization Clinic Stem Cells “Blueprint” cells A Blastocyst is a hollow ball of cells with a small clump of stem cells inside Stem Cells “Blueprint” cells

10. Neuron Muscle cell Pancreatic Islet Petri Dish Stem Cells Different chemicals / molecules are added to the stem cells to make them become specific types of cells. Growth factors Chemical cues

12. Donor Egg Skin Cell Needle Nucleus (DNA) Nucleus (DNA) Needle Chemicals and Growth Factors Dividing cells Neuron Muscle cell Pancreatic Islet Stem Cells Somatic Cell Nuclear Transfer or Therapeutic Cloning Blastocyst Stem Cells

13. The vision for UCI’s Stem Cell Center: Stem cell therapies for neurological disorders Brain and spinal cord injury. Stroke. Neurodegenerative diseases  Parkinson’s Disease  Huntington’s Disease  Alzheimer’s Disease  Multiple Sclerosis  Lou Gerhig’s Disease (ALS) Reeve-Irvine Research Center

14. Neurological disorders involve the loss of particular cell types in the nervous system Brain and spinal cord injury and stroke (loss of nerve cells and myelin-forming oligodendrocytes). Neurodegenerative diseases  Parkinson’s Disease (loss of dopamine-containing nerve cells in the brainstem).  Huntington’s Disease (loss of nerve cells in the striatum).  Alzheimer’s Disease (loss of nerve cells in the cerebral cortex).  Multiple Sclerosis (loss of myelin-forming oligodendrocytes).  Lou Gerhig’s Disease-ALS (loss of motor neurons from the spinal cord). The vision: To use embryonic stem cells to restore the cells that are lost as a result of injury or neurodegenerative diseases. Reeve-Irvine Research Center

15. Blastocyst - Stem Cells Pipette Stem Cells “Blueprint” cells Stem Cells Petri Dish “Blueprint” cells Goal #1: to make stem cells into nerve cells The stem cells are treated with factors to cause them to differentiate into particular cell types Stem cells differentiated into neurons Reeve-Irvine Research Center

16. Goal #2: To discover how to make stem cells integrate into neural circuits. Reeve-Irvine Research Center Nerve cell (neuron) Oligodendrocyte More research is needed to find the ways to actually use stem cells for therapeutic applications.

17. At the RIRC, a therapy is being developed to use stem cells to replace myelin-forming cells Myelin-forming cells (oligodendrocytes) die as a result of spinal cord injury, resulting in the loss of myelin (insulation) from nerve fibers. An important potential therapeutic strategy: Replace myelin-forming cells using stem cells that differentiate into oligodendrocytes. Reeve-Irvine Research Center

18. Then to Oligodendrocyte Precursors Stem cells are first differentiated to the neural lineage. RIRC scientists have succeeded in developing ways to produce oligodendrocytes from human ES cells and have shown that they can restore myelin after spinal cord injury in experimental animals. Keirstead Lab Reeve-Irvine Research Center

19. But do these cells have the potential to form tumors over longer periods of time?

20. 1.They can generate large quantities of tissue rapidly 2. They can become any cell in the body Embryonic stem cells Brain Heart Cartilage Bone marrow Fat Embryonic Stem Cells Human Embryonic Stem Cells

21. Developing facilities for stem cell research It is likely that research involving non-approved stem cell lines will be prohibited in facilities that were built with NIH support, or that contain NIH-supported core equipment. In recognition of this, up to 10% of Prop. 71 funds will be used to build scientific and medical research facilities. Funding through Prop. 71 for development of facilities requires a 20% match. Reeve-Irvine Research Center

22. Proposition 71: Funds Indirect costs limited to 25 % of a research award  Excluding amounts included in a facilities award  Indirect cost limitation may be increased by amount the grantee provides in matching funds  Must be in excess of 20% of the grant amount