Stem Cell therapy.ppt
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The document discusses potential applications of stem cell therapies, including using induced pluripotent stem cells (iPSCs) to treat Parkinson's disease and blood disorders, and using human embryonic stem cells (hESCs) to treat spinal cord injury. It provides details on a phase 1 clinical trial by Geron using oligodendrocyte progenitor cells derived from hESCs to treat spinal cord injury. The document also discusses how hematopoietic stem cell transplants are used to treat various cancers and autoimmune diseases. It describes techniques such as fluorescence activated cell sorting that are used to isolate hematopoietic stem cells.
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Stem Cell therapy.ppt
- 1. Doug Brutlag 2011 Genomics, Bioinformatics & Medicine http://biochem158.stanford.edu/ Doug Brutlag Professor Emeritus of Biochemistry & Medicine Stanford University School of Medicine Stem Cell Therapies http://biochem158.stanford.edu/Stem%20Cell%20Therapies.html
- 2. Doug Brutlag 2011 Stem Cell Promise & Stem Cell Therapeutics http://www.stemcelltherapies.org/ Parkinsons 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. Doug Brutlag 2011 Geron Stem Cell Therapy Tom Okarma - Geron
- 4. Doug Brutlag 2011 Human Embryonic Stem Cells Tom Okarma - Geron
- 5. Doug Brutlag 2011 Spinal Cord Injury Pathology at the Lesion Tom Okarma - Geron
- 6. Doug Brutlag 2011 GRNOPC1 Improves Locomotor Behavior after Spinal Cord Injury Tom Okarma - Geron
- 7. Doug Brutlag 2011 Spinal Cord Injury http://www.geron.com/GRNOPC1Trial/
- 8. Doug Brutlag 2011 GRNOPC1 Induces Remyelination after Spinal Cord Lesions in Rodents Tom Okarma - Geron
- 9. Doug Brutlag 2011 GRNOPC1 Promotes Neural Outgrowth Tom Okarma - Geron
- 10. Doug Brutlag 2011 Human Embryonic Stem Cell (hESC) Based Therapy Tom Okarma - Geron
- 11. Doug Brutlag 2011 Geron Oligodendrocyte Progenitor Cells GRNOPC1 Tom Okarma - Geron
- 12. Doug Brutlag 2011 GRNOP1 Phase 1 Multi-Center Spinal Cord Injury Trial Tom Okarma - Geron
- 13. Doug Brutlag 2011 Clinical Trials Database http://clinicaltrials.gov/
- 14. Doug Brutlag 2011 Stem Cell Clinical Trials http://clinicaltrials.gov/
- 15. Doug Brutlag 2011 Geron Clinical Trials http://clinicaltrials.gov/
- 16. Doug Brutlag 2011 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
- 18. Doug Brutlag 2011 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. Doug Brutlag 2011 Autologous vs. Allogeneic Transplants Judith Shizuru Unfractionated bone marrow or mobilized blood Donor blood formation, graft-vs-tumor effect Purify from Tumor cells Transplant Transplant Autologous Allogenic Healthy Donor
- 20. Doug Brutlag 2011 Complications of Allogeneic Transplants Transplant related mortality = 10 - 15% Regimen related toxicity Infectious complications Engraftment failure (resistance) Graft-versus-host disease Judith Shizuru
- 21. Doug Brutlag 2011 Judith Shizuru
- 22. Doug Brutlag 2011 Cells of the Bone Marrow Judith Shizuru
- 23. Doug Brutlag 2011 Regulation of hematopoiesis by cytokines http://www.biocarta.com/pathfiles/h_stemPathway.asp
- 24. Doug Brutlag 2011 Isolation of Hematopoietic Stem Cells Judith Shizuru
- 25. Doug Brutlag 2011 Fluorescent Activated Cell Sorter (FACS) Herzenberg & Herzenberg http://www.bio.davidson.edu/courses/genomics/method/FACS.html
- 26. Doug Brutlag 2011 Why Transplant Purified Allogeneic HSCs? Judith Shizuru
- 27. Doug Brutlag 2011 Engraftment Resistance is Significant Obstacle to HSC Transplantation Judith Shizuru
- 28. Doug Brutlag 2011 Experimental Autoimmune Encephalomyelitis (EAE) Model for Multiple Sclerosis in Mice Judith Shizuru MOG MOG MOG
- 29. Doug Brutlag 2011 Partial Chimerism Results in Disease Amelioration 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 0 .0 0 0 .2 5 0 .5 0 0 .7 5 1 .0 0 Time (days ) T cells B cells Macrop ha ges Granulocytes 5 4 3 2 1 0 +60 -35 +60 TBI & HSC TLI + ATG TBI TLI + ATS HSC 5 4 3 2 1 0 Judith Shizuru
- 30. Doug Brutlag 2011 Other Applications of Hematopoietic 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. Doug Brutlag 2011 Combined HSC & islet transplantation Judith Shizuru
- 32. Doug Brutlag 2011 Treatment of Diabetic Mice (NOD) with Hematopoietic Stem Cell Transplants NOD male controls NOD female controls Months after birth Diabetes free (%) 100 80 60 40 20 0 0 2 4 6 8 10 12 14 NOD WBM NOD AKR HSC NOD txp NOD HSC NOD Judith Shizuru
- 33. Doug Brutlag 2011 Hematopoietic Cell Treatment Coupled with High Dose Breast Cancer Chemotherapy Stage Four Metastatic Breast Cancer M端ller et al. (2011) Biol. Blood Marrow Transplant