Demystifying Stem Cells
Brent Bost M.D., CPA, MBA, FACOG
Disclaimers
• Author currently serves on Board of Directors of CordTrack
• Most applications discussed today are not currently FDA approved and are, by definition, considered experimental
– Must be paid for by the patient
– Some are becoming common practice
Hematopoietic Stem Cells (HSCs)
• Sources
– Cord blood
– Blood filtering
– National Bone Marrow Registries
• Autologous BMTs – Immunosuppresant
therapy not required
• Recent advances in expansion
Mesenchymal Stem Cells (MSCs)
• Found in – Cord Tissue
– Adipose
– Collagenous portion of Bone Marrow Aspirate
• Expand rapidly
– 1 cm of cord tissue produces 1 billion stem cells after 30 days incubation
• Immuno‐priveleged
– Are not recognized by the immune system
Stem Cell Mechanisms of Action
• Replace dead cells
– (If they are a sufficiently close genetic match)
Stem Cell Mechanisms of Action
• Replace dead cells
– (If they are a sufficiently close genetic match)
• Modify Micro(local)/Macro (global)‐environment
Stem Cell Mechanisms of Action
• Replace dead cells
– (If they are a sufficiently close genetic match)
• Modify Micro(local)/Macro (global)‐environment
• Alter local cellular metabolism
– Eliminate anaerobic metabolites (↓ inflamma on)
– Prevent/slow apoptosis
Stem Cell Mechanisms of Action
• Replace dead cells
– (If they are a sufficiently close genetic match)
• Modify Micro(local)/Macro (global)‐environment
• Alter local cellular metabolism
– Eliminate anaerobic metabolites (↓ inflamma on)
– Prevent/slow apoptosis
• Mask immune response (via cytokines)
↓ Immunologic‐induced tissue destruction
‐ humoral and cell‐mediated
↓ Nonspecific immune response
Stem Cell Mechanisms of Action
• Replace dead cells
– (If they are a sufficiently close genetic match)
• Modify Micro(local)/Macro (global)‐environment
• Alter local cellular metabolism
– Eliminate anaerobic metabolites (↓ inflamma on)
– Prevent/slow apoptosis
• Mask immune response (via cytokines)
↓ Immunologic‐induced tissue destruction
‐ humoral and cell‐mediated
↓ Nonspecific immune response
• Produce bactericidal / static substances Stem Cell Mechanisms of Action
• Replace dead cells
– (If they are a sufficiently close genetic match)
• Modify Micro(local)/Macro (global)‐environment
• Alter local cellular metabolism
– Eliminate anaerobic metabolites (↓ inflamma on)
– Prevent/slow apoptosis
• Mask immune response (via cytokines)
↓ Immunologic‐induced tissue destruction
‐ humoral and cell‐mediated
↓ Nonspecific immune response
• Produce bactericidal / static substances • Induce angiogenesis at site of injury
Stem Cell Mechanisms of Action
• Replace dead cells
• Modify Micro(local)/Macro (global)‐environment
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Alter local cellular metabolism
Mask immune response (via cytokines)
Produce bactericidal / static substances Induce angiogenesis at site of injury
Induce pericytes in the host tissue vessels to become
the tissue‐specific stem cells required for tissue
repair
Stem Cell Mechanisms of Action
• Replace dead cells
• Modify Micro(local)/Macro (global)‐environment
Alter local cellular metabolism
Mask immune response (via cytokines)
Produce bactericidal / static substances Induce angiogenesis at site of injury
Induce pericytes in the host tissue vessels to become
the tissue‐specific stem cells required for tissue
repair
** engraftment of donor stem cells seldom occurs
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Stem Cell Sources
• NMDP
– $50,000 per sample
– 2 Samples per BMT
• Bone marrow aspirate
• Cord blood/tissue
• Commercial preparations
– Pharmaceutical pricing model estimate: $20,000 to $30,000 per sample
• Adipose liposuction
– $8,000 to $10,000 per sample
• Other sources
Processing Cord Blood
1. Shipped via FedEx/Courier
2. Excess plasma is removed
3. RBCs removed
4. Cryoprotectant added
5. Controlled rate freeze
6. Nitrogen tanks
Traditional Cord Blood Storage
• Single bag storage 80:20 bag
Traditional Cord Blood Storage
• Single bag storage 80:20 bag
same processing requirements in private storage vs. public donation
Why Umbilical Cord Tissue?
Mesenchymal stem cells
Why Umbilical Cord Tissue?
Mesenchymal stem cells
Main functions in regenerative medicine
Why Umbilical Cord Tissue?
Mesenchymal stem cells
Main functions in regenerative medicine
‐ stop inflammation
‐ mask immune response
‐ bacteriocidal
‐ induce angiogenesis
Why Umbilical Cord Tissue?
Mesenchymal stem cells
Main functions in regenerative medicine
‐ stop inflammation
‐ mask immune response
‐ bacteriocidal
‐ induce angiogenesis
*stem cells induce pericytes in host
tissue blood vessels to become the tissue‐specific stem cells required for tissue repair.
Why Umbilical Cord Tissue?
Mesenchymal stem cells
Main functions in regenerative medicine
‐ stop inflammation
‐ mask immune response
‐ bacteriocidal
‐ induce angiogenesis
*stem cells induce pericytes in host
tissue blood vessels to become the tissue‐specific stem cells required for tissue repair. (Often no engraftment occurs . . .)
Progression of Stroke
• Ischemic event triggers
– Anaerobic metabolites accumulate
– Inflammation
– Ischemic cell death
– Apoptosis of damaged but still viable cells
Stem Cell Therapy in Stroke
• Alter metabolism to clear anaerobic metabolites
• Reduce tissue destruction of inflammation response
• Prevent apoptosis
• Stimulate multiplication and migration of indigenous stem cells to affected area to replace dead cells
• Promote rapid growth of new vascular beds
Target Disorders of Stem Cell Therapy
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Autoimmune Disorders
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Myocardial Infarction:
Valve Repair
PAD Peripheral Artery Occlusive Disease
CHD
Neurologic Disorders
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ALS Amyotrophic Lateral Sclerosis
Cerebral Palsy
Stroke
Spinal Cord Injury
Parkinson’s Disease
Alzheimer’s Disease
Orthopedic Conditions
– Degenerative Disc Disease
– Cartilage, Tendon and Ligament Repair
– Bone Repair
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Cardiovascular Diseases
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Type 1 Diabetes
Multiple Sclerosis
Rheumatoid Arthritis
Lupus
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Pulmonary Disorders
– (COPD)
– Lung Injury
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General and Regenerative Medicine
Burns, Wounds, Scars
Deafness
Missing Teeth
Blindness, Macular Degeneration and Vision Impairment
– Baldness
– Liver Disease
– Post Mastectomy Cosmetic Breast Reconstruction
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How Stem Cells Are Retrieved
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Patient’s Physician suggests stem cells as a possible therapy
Parents inform MD that they have their child’s cord blood and tissue stem cells stored
Physician has their treatment center contact Bank to obtain stem cells
Bank sends parents the release forms to authorize release
Treatment center makes shipping arrangements
Cells shipped still frozen
Shipping costs are usually included in the treatment costs
Donation
• National Marrow Donor Program (NMDP)
– Hospital Claim Waivers eliminated 2013
– Procedure • Decide around week 28 at glucose testing time
– Federal screening survey is sent and returned
– Donation kit shipped to patient
• Blood collection
– Exactly like private storage
» Kit is given back to the patient
» Patient calls the number on the kit
• Only a donation kit may be used for collection
• Should NEVER cost the patient a penny
– (there should be no shipping, kit or processing fees)
Donation • Thousands of donations are collected before even one is sold
• Government subsidies help these banks survive
• No weekend donations
– Shipping costs skyrocket
• No twin donations
– 2 kits would be used but volume is never sufficient
• Volume requirements
The Future of Cord Blood Storage
‐ 1:3 people will be able to benefit from Stem Cell Therapies in the future
‐ Stem cell expansion technology will become more
efficient
‐ Cost for SCT will rise initially, then fall over time
‐ “Whole Cell” Therapies will be augmented by 1) Targeted therapies
2) Generic, sub‐cellular technology
Questions