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Genomics , Bioinformatics & Medicine http://biochem158.stanford.edu/

Genomics , Bioinformatics & Medicine http://biochem158.stanford.edu/. Stem Cell Therapies http://biochem158.stanford.edu/Stem%20Cell%20Therapies.html. Doug Brutlag Professor Emeritus of Biochemistry & Medicine Stanford University School of Medicine.

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Genomics , Bioinformatics & Medicine http://biochem158.stanford.edu/

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  1. Genomics, Bioinformatics & Medicinehttp://biochem158.stanford.edu/ Stem Cell Therapies http://biochem158.stanford.edu/Stem%20Cell%20Therapies.html Doug Brutlag Professor Emeritus of Biochemistry & Medicine Stanford University School of Medicine

  2. Stem Cell Promise & Stem Cell Therapeuticshttp://www.stemcelltherapies.org/ • Parkinson’s Disease with iPSCs • Spinal Cord Injury with human embryonic stem cells (hESCs) • Sickle Cell, Thalassemias, hemophilia and other blood diseases with iPSCs • Bone Marrow Transplants (BMT) & hematopoietic stem cell therapy (HCT) • Lymphomas and thymomas • Hematopoietic cells • Metastatic cancers of other origins • Autoimmune Diseases with hematopoietic stem cells (HSCs) • Rheumatoid arthritis • Systemic Lupus Erythematosus • Type 1 diabetes mellitus • Multiple sclerosis • Pernicious anemia

  3. Geron Stem Cell Therapy Tom Okarma - Geron

  4. Human Embryonic Stem Cells Tom Okarma - Geron

  5. Spinal Cord InjuryPathology at the Lesion Tom Okarma - Geron

  6. GRNOPC1 Improves Locomotor Behavior after Spinal Cord Injury Tom Okarma - Geron

  7. Spinal Cord Injuryhttp://www.geron.com/GRNOPC1Trial/

  8. GRNOPC1 Induces Remyelination after Spinal Cord Lesions in Rodents Tom Okarma - Geron

  9. GRNOPC1 Promotes Neural Outgrowth Tom Okarma - Geron

  10. Human Embryonic Stem Cell (hESC)Based Therapy Tom Okarma - Geron

  11. Geron Oligodendrocyte Progenitor Cells GRNOPC1 Tom Okarma - Geron

  12. GRNOP1 Phase 1 Multi-CenterSpinal Cord Injury Trial Tom Okarma - Geron

  13. Clinical Trials Databasehttp://clinicaltrials.gov/

  14. Stem Cell Clinical Trialshttp://clinicaltrials.gov/

  15. Geron Clinical Trials http://clinicaltrials.gov/

  16. Clinical Trials of Hematopoietic Cell Transplantation Judith A. Shizuru, M.D., Ph.D. Division of Blood and Marrow Transplantation Stanford University Medical Center Judith Shizuru

  17. Hematopoiesis http://www.biocarta.com/pathfiles/h_stemPathway.asp

  18. Bone Marrow Transplants to Cure Lymphomas/Thymomas • Whole Body Irradiation to remove endogenous immune system and tumor • Also total lymphoid irradiation with antithymocyte serum • Injection of bone marrow from a well matched donor to re-establish immune system • Regulation of immune response to prevent graft versus host reaction. • Autologous donation possible if one can purify and remove tumor cells, enriching for stem cells.. • Allogeneic donors have advantage of graft versus tumor reaction to kill any remaining tumor cells. • Allogeneic donors have the disadvantage of graft versus host reaction if they are not well matched. Judith Shizuru

  19. Autologous vs. Allogeneic Transplants Autologous Allogenic Healthy Donor Purify from Tumor cells Unfractionated bone marrow or mobilized blood Transplant Transplant Donor blood formation, graft-vs-tumor effect Judith Shizuru

  20. Complications of Allogeneic Transplants Transplant related mortality = 10 - 15% • Regimen related toxicity • Infectious complications • Engraftment failure (resistance) • Graft-versus-host disease Judith Shizuru

  21. Judith Shizuru

  22. Cells of the Bone Marrow Judith Shizuru

  23. Regulation of hematopoiesis by cytokineshttp://www.biocarta.com/pathfiles/h_stemPathway.asp

  24. Isolation of Hematopoietic Stem Cells Judith Shizuru

  25. Fluorescent Activated Cell Sorter (FACS)Herzenberg & Herzenberg http://www.bio.davidson.edu/courses/genomics/method/FACS.html

  26. Why Transplant Purified Allogeneic HSCs? Judith Shizuru

  27. Engraftment Resistance is Significant Obstacle to HSC Transplantation Judith Shizuru

  28. Experimental Autoimmune Encephalomyelitis (EAE) Model for Multiple Sclerosis in Mice MOG MOG MOG Judith Shizuru

  29. 543210 TLI + ATS TBI 5 4 3 2 1 0 +60 +60 -35 TLI + ATG TBI & HSC HSC Partial Chimerism Results inDisease Amelioration Judith Shizuru

  30. Other Applications ofHematopoietic Stem Cell Transplantation • Treatment of autoimmune disease • Patients treated with bone marrow transplants are often cured of autoimmune disease • Bone marrow transplant donors with autoimmune disease can pass the disease on to recipients • Organ tolerance induction • Mice receiving organ transplant and HSC transplant together are tolerant and no rejection occurs. No immune suppressants are needed. Judith Shizuru Judith Shizuru

  31. Combined HSC & islet transplantation Judith Shizuru

  32. 100 NOD male controls NOD female controls 80 NOD WBM NOD 60 NOD HSC NOD Diabetes free (%) AKR HSC NOD 40 txp 20 0 0 2 4 6 8 10 12 14 Months after birth Treatment of Diabetic Mice (NOD) withHematopoietic Stem Cell Transplants Judith Shizuru

  33. Hematopoietic Cell Treatment Coupled withHigh Dose Breast Cancer Chemotherapy Stage Four Metastatic Breast Cancer Müller et al. (2011) Biol. Blood Marrow Transplant

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