1. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Clinical Trials

2. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Clinical Trials 1.Advanced Cell Technology: embryonic stem cells, hemangioblasts (FDA approved) Macular degeneration, vascular repair, skin repair 2.Cytori: Adipose stem cells breast reconstruction, Heart repair 3.Geron: Embryonic stem cells (FDA approved) Spinal repair, heart repair, diabetes, osteoarthritis, osteoporosis 4.OncoMed: cancer stem cells Solid tumors 5.Osiris: Mesenchymal stem cells Graft-vs-Host disease, heart repair, bone and cartilage repair 6. Stem cells Inc.: Fetal neural stem cells (FDA approved) Batten Disease (lysosomal storage disorders) 7.Tengion: Tissue engineering

3. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Clinical Trials

4. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Clinical Trials Most clinical trials fail Ismail Kola & John Landis Nature Reviews Drug Discovery 3, 711-716 (August 2004)

5. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Clinical Trials Advanced Cell Technology 1)Terminally differentiated cells made from human embryonic stem cells. Retinal pigment epithelial cells for Stargardt’s Macular Dystrophy and macular degeneration. 2)Animal studies = no tumors. 3)Detection sensitivity less than 1:1,000,000 cells (in vitro=in vivo?) 4)50,000 cells per transplant 5)Twelve patients enrolled, none transplanted

6. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Clinical Trials Stem Cells Inc. 1)Neural cells made from fetal neural stem cells for Batten Disease, a fatal condition with cognitive disorders. Bore holes into the skull, into which stem cells are injected. 2)Subjects for the trial were children pre-teen and younger, raising issues about informed consent and expectations of benefit in a safety trial. 3)Such trials for patients must not be “greater than minimal risk”. Placebos in high-risk trials are controversial, so-called “sham surgeries”. 4)Six patients enrolled, one died from disease progression. Trial terminated in April because of lack of enrollment in Phase 1b.

7. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Clinical Trials Geron Corporation 1)Oligondendrocytes derived from H9, a human embryonic stem cell line 2)Human subjects 18-65 years old, recently injured with single spinal contusion (not severing or penetration). Must have procedure between 7 and 14 days of administration. 50,000 people suffer spinal injuries every year in US 3)2,000,000 cells administered. 4)Three procedures: Stabilize the injury at a trauma center, receive the transplant, undergo intensive physical therapy

8. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Clinical Trials

9. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Clinical Trials

10. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Clinical Trials: Heart Disease

11. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Diseases of heart muscle tissue Diseases of cardiac muscles Congestive heart failure, or ineffective pumping due to cardiomyocyte dysfunction, affects 4.8 million people in U.S. Heart attack, also known as myocardial infarction Heart arrhythmias, or abnormal activity (palpitations) 1% of live births display a congenital heart defect

12. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Fill in the blank myocardial cells & hematopoetic cells 12 ??? ?

13. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Heart and blood Sharing an ancestor Cardiomyocyte Lateral plate mesodermal cell Cardiogenic mesodermal cell Differentiation Lineage restriction 13 FGF8 Anterior lateral plate mesodermal cell Posterior lateral plate mesodermal cell Hemangiogenic mesodermal cell Blood cells Fetal StageAdult Stage

14. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Clinical Trials: Heart Disease Autologous (from you, to you) transplants into patients with end-stage cardiac disease Cells used from bone marrow First Brazil, Portugal, then the UK (BOOST) trial in 2004 Highest number of stem cell trials of any type (not counting cancer trials)

15. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Clinical Trials: Heart Disease

16. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Clinical Trials: Heart Disease

17. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Clinical Trials: Heart Disease Phase 0 or 1 studies Not all studies are FDA approved Most studies in other countries Heart HSC trials increasing About 140 clinical trials now

18. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Discussion: discoveries, companies, and products What motivates scientists? Businesses? How do biotechnology companies start? Survive? What obligations do biotechnology companies have to society?

19. References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Activity 2: Public Policy Panel Discussion Consensus statements and discussion: grading scheme Presentation and Organization: state position clearly; present argument in logical order; respectful and engaging writing and presentation style. Science Understanding: Use accurate scientific vocabulary, facts, and concepts; present information to support argument both scientifically, ethically, and socially; understand implications of science policy Logic & Reasoning: Give arguments with sound reasoning; draw on references from assigned readings and research; use strong concise points, use supporting evidence; interpret evidence correctly; address challenges with counter arguments 19