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

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Genomics, Bioinformatics Medicinehttp//biochem
158.stanford.edu/
Stem Cell Therapies http//biochem158.stanford.edu
/Stem20Cell20Therapies.html
Doug Brutlag Professor Emeritus of Biochemistry
Medicine Stanford University School of Medicine
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Stem Cell Promise Stem Cell Therapeuticshttp//
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

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Geron Stem Cell Therapy
Tom Okarma - Geron
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Human Embryonic Stem Cells
Tom Okarma - Geron
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Spinal Cord InjuryPathology at the Lesion
Tom Okarma - Geron
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GRNOPC1 Improves Locomotor Behavior after Spinal
Cord Injury
Tom Okarma - Geron
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Spinal Cord Injuryhttp//www.geron.com/GRNOPC1Tri
al/
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GRNOPC1 Induces Remyelination after Spinal Cord
Lesions in Rodents
Tom Okarma - Geron
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GRNOPC1 Promotes Neural Outgrowth
Tom Okarma - Geron
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Human Embryonic Stem Cell (hESC)Based Therapy
Tom Okarma - Geron
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Geron Oligodendrocyte Progenitor Cells GRNOPC1
Tom Okarma - Geron
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Properties of GRNOP1
Tom Okarma - Geron
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GRNOP1 Phase 1 Multi-CenterSpinal Cord Injury
Trial
Tom Okarma - Geron
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Clinical Trials Databasehttp//clinicaltrials.gov
/
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Stem Cell Clinical Trialshttp//clinicaltrials.go
v/
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Geron Clinical Trials http//clinicaltrials.gov/
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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
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Hematopoiesis http//www.biocarta.com/pathfiles/h
_stemPathway.asp
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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
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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
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Complications of Allogeneic Transplants

• Transplant related mortality 10 - 15
• Regimen related toxicity
• Infectious complications
• Engraftment failure (resistance)
• Graft-versus-host disease

Judith Shizuru
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Judith Shizuru
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Cells of the Bone Marrow
Judith Shizuru
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Regulation of hematopoiesis by cytokineshttp//ww
w.biocarta.com/pathfiles/h_stemPathway.asp
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Hematopoietic Idiotype Markers
Weisman and Shizuru (2008) BLOOD112, Pages
3543-3553, 2008.
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Isolation of Hematopoietic Stem Cells
Judith Shizuru
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Fluorescent Activated Cell Sorter
(FACS)Herzenberg Herzenberg
http//www.bio.davidson.edu/courses/genomics/metho
d/FACS.html
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Why Transplant Purified Allogeneic HSCs?
Judith Shizuru
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Engraftment Resistance is Significant Obstacle to
HSC Transplantation
Judith Shizuru
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Experimental Autoimmune Encephalomyelitis (EAE)
Model for Multiple Sclerosis in Mice
MOG
MOG
MOG
Judith Shizuru
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Partial Chimerism Results inDisease Amelioration
Judith Shizuru
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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
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Combined HSC islet transplantation
Judith Shizuru
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Treatment of Diabetic Mice (NOD)
withHematopoietic Stem Cell Transplants
Judith Shizuru
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Hematopoietic Cell Treatment Coupled withHigh
Dose Breast Cancer Chemotherapy
Stage Four Metastatic Breast Cancer
Müller et al. (2011) Biol. Blood Marrow
Transplant