Stem Cell Research From Bench to Bedside

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Georgiana Stokes
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1 Stem Cell Research From Bench to Bedside Stem Cell Dialogues Jan A. Nolta, Ph.D. Professor, Internal Medicine Director, UC Davis Institute for Regenerative Cures October 26, 2010

2 Stem Cells at UC Davis Research fills a void in medicine The future is here, now Unique facilities Team approach

3 The importance of stem cells

4 Types of stem cells Adult Stem Cells Blood forming (hematopoietic) Mesenchymal (supporting cells) Pluripotent Cells Embryonic Induced pluripotent stem cells

5 Adult stem cell therapies began in 1956 Bone marrow transplantation Millions of lives saved Stem cell Homing

6 Mesenchymal Stem Cells (MSC) are tissue-repairing adult stem cells Bone Marrow Harvested from brave donors Adipose tissue From liposuction or surgery

7 Mesenchymal stem cells Adult stem cells that cannot create an entire tissue Strong safety profile Paramedics

8 Human MSC migrate rapidly and interact with many cells, Video by Scott Olson, Ph.D., Nolta lab

9 Marrow stem cells home from the bloodstream to sites of tissue injury injured leg healthy leg

10 Human Stem Cell Tracking Human stem cells are labeled Dynamic tracking in live rodent

11 Human stem cells home from the bloodstream to the site of myocardial infarction Inject stem cells IV MI model In mouse Homing to area of low oxygen Sondergaard and Nolta, Journal of Translational Medicine, 2010

12 Update- Stem cell cardiac clinical trials done in USA- preliminary results Patients receiving mesenchymal stem cells (Osiris Prochymal) did better than those receiving only standardof-care Fewer side effects and significant improvements in heart, lung and global function compared to the placebo group Important step forward in the search for stem cell treatments for heart disease. With a strong safety profile that now includes more than 1,000 patients studied in clinical trials, MSC are in a position to make significant advances in the field of cardiology."

13 Delivery methods: Intravenous delivery: Cells find the damage Dr. Southard, UCD Delivery on a scaffold : Replacement of structures Dr. Boyd, UCD Google: UCD stem cell dialogs for video

14 Cell Delivery on a scaffold : For replacement of entire structures Nature s Trellis

15 Nature s platform for implanting cells Synthetic matrix Does not have the innate structure of the organ Several types available Decellularized matrix All cells have been stripped away No immune system attack if done properly Intricate structure is maintained by the supporting proteins Nature s platform to rebuild the organ

16 Decellularized scaffolds Heart Heart during the washing process- Cells are removed Decellularized heart Ott et al, Nature Medicine

17 Decellularized liver Zhou and Wu, Nolta and Zern labs 2010

18 vasculature is maintained in decellularized tissue

19 Green-labeled stem cells lodge into the stripped vasculature of the decellularized tissue after injection, then migrate out into the tissue

20 Human Liver Cells Growing in Decellularized Liver Matrix Prior to Transplantation

21 Human hepatocytes viewed inside living mice: ACells implanted on decellularized B liver scaffold retain good survival and function A) Cells implanted on decellularized liver scaffold: Excellent retention 3 months B) Cells transplanted by injectionno scaffold: Scattering/poor retention Zhou, Nolta, Zern, Wu Manuscript submitted 2010

23 Neo-organs from human tissue grown in mice

24 Developing Cell and Organ Replacement for Individual Patients Skin fibroblastsfrom the patient Induced pluripotent stem cells Patient-specific human Hepatocytes in culture Transplant Into patient Place on scaffold

25 Unique facilities

26 From the lab to the patient and back to the lab

28 UC Davis Good Manufacturing Practice facility

30 Team science

31 Hearing loss Neurodegenerative disease Heart disease Bladder disease Skin repair Peripheral vascular disease Cancer relapse Eye disease Lung disease Osteoporosis Kidney disease Liver disease Blood disorders Immune system disorders

32 Collaboration: a key to success UC Davis Stem Cell Program partners Medical Center School of Medicine Veterinary Medicine Biomedical Engineering MIND Institute Center for Biophotonics Shriners Hospital VA Hospital Sac State Industry partners

33 Clinical Trials Of Stem Cell Therapies at UC Davis Disease Timing Bone fractures 2008 Heart attack 2009 Peripheral vascular disease 2010 Blindness To be announced Huntington s disease & ALS To be announced Liver disease To be announced Many more are on the way, under development

34 Questions What kinds of stem cells are best to renew each tissue? How do we take cells safely through nature s path to rebuild tissues and organs?

35 Funding California Institute for Regenerative Medicine (Prop. 71) National Institutes of Health Private philanthropy

36 Thank You Stem Cell Dialogues Jan A. Nolta, Ph.D. Professor, Internal Medicine Director, UC Davis Institute for Regenerative Cures July 28, 2010

Regenerative Medicine and Stem Cell Therapies

Regenerative Medicine and Stem Cell Therapies Regenerative Medicine Major component of successful regenerated / tissue engineered organs Scaffolds A critical element is the binding of the repopulating