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WHY stem cell research?. Potential medical applications. Stem cells produce new cells Adult: replace damaged/lost cells Embryonic: build the organism Can this power be harnessed to produce new cells artificially?. Potential medical applications. - PowerPoint PPT Presentation
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WHY stem cell research?
Potential medical applications
• Stem cells produce new cells– Adult: replace damaged/lost cells– Embryonic: build the organism
Can this power be harnessed to produce new cells artificially?
Potential medical applications
• Manipulate stem cells: replace lost/damaged cells
– Injury• Burns, spinal cord damage (paralysis)
– Degenerative diseases• Heart disease, juvenile diabetes, Parkinson’s
– “Non-degenerative” diseases• Cancer?
General Procedure
• Isolate highly potent stem cells
• Coax SC to differentiate into the needed specialized cell
• Introduce differentiated cells to the site of damage
• Cells formerly known as stem cells replace the lost cells
DAMAGED TISSUE
One way: ‘Niche’-directed differentiation
HEALTHY TISSUE
Cultured stem cellsin the lab
DELIVER (inject/transplant)the cultured SC
Cells ‘home in’on the site of injury
Peer pressure:Neighbors cause SC todifferentiate appropriately
Leukemia treatment“Bone marrow transplants”
• Cancer of the blood cell progenitors
• Rapid production of blood cells– Acute: high # of immature blood cells crowd bone
marrow– Chronic: high output of abnormal blood cells
• Lack of normal blood cells:– Platelets…clotting disorders– White blood cells…propensity for infection– Red blood cells…anemia
Production of blood cells occurs in the bone marrow
(One form of…) Stem Cell Treatment
• Kill patient’s bone marrow– Radiation/chemotherapy– Destroys cancerous (and healthy) stem cells
• Patient needs RBC, platelets from donors• Highly susceptible to infection
– Now it’s a ‘degenerative disease’
• Refurbish the bone marrow– ‘Healthy’ stem cells
• Patient’s own bone marrow, treated to enrich for healthy cells• Healthy donor
– Stem cells ‘move in’ to the bone marrow, start making new blood cells
Problems…
• Susceptibility to infection before new stem cells kick in
• Stem cells may not ‘take’
• Graft-vs-Host disease– New immune system attacks the recipient
• Skin, liver, intestinal tract
DAMAGED TISSUE
Another way: Factor-directed differentiation
HEALTHY TISSUE
Culture stem cellsin the labAdd a chemical factorto induce differentiationAllow cells to differentiateappropriately
DELIVER (inject/transplant)the differentiated cells
Cells heal the damage
Factor-directed differentiation
• Retinoic acid + insulin: fat cells
• Retinoic acid: nervous system
• Retinoic acid + DMSO: muscle cells
• Interleukin-3: neurons, white blood cells
• Niche-directed differentiation– Advantages
• Don’t need to know a whole lot about the cells
(Let the ‘niche’ do the dirty work)
– Disadvantages• Will all the cells differentiate appropriately?
(Remember the teratoma)
• Factor-directed differentiation– Advantages
• More control over the identity of the delivered cells
– Disadvantages• More research needed to determine the correct
factors (may be impossible in some cases)• Too differentiated? Lose proliferation?
• Niche- vs. factor-directed differentiation
– Ultimate answer: hybrid between the two?
• Paralysis (spinal cord injuries)
• Juvenile diabetes
• Parkinson’s
Spinal cord injuries
Hwang Mi-Soon: South Korea
Paralyzed 19 years
Multipotent adult stem cells injected into her spinal cord
Currently: debilitating pain
Published in 2005 (Cytotherapy)
Success of stem cell therapy?
Dr. Hans Keirstead
• Use of human embryonic stem cells to ‘cure’ paralyzed rats
• Partially differentiate in culture (factor-directed)
• Inject into the spinal cord
• http://www.hopkinsmedicine.org/Press_releases/2006/images/video1.wmv
• http://www.hopkinsmedicine.org/Press_releases/2006/images/video2.wmv
• http://www.uci.edu/experts/video.php?src=keirstead&format=mov&res=high
• Trials in humans ‘soon’…one to two years?– Need to convince FDA that it’s safe enough…
and ethically responsible
Juvenile (Type I) Diabetes
• Insulin: hormone that regulates the amount of sugar in the blood
• Lots of sugar: insulin released by the pancreas (islet cells)– Tells cells (mainly muscle & fat cells) to take
up sugar from the blood stream
Diabetes mellitus
• “Sweet urine”– High blood sugar
• Cells don’t take up sugar appropriately
• Type I: pancreas doesn’t make insulin– Inject insulin
• Type II: cells don’t respond to insulin– “Non-insulin dependent”
Type I Diabetes
• “Auto-immune disorder”– Your immune system attacks your own body– Pancreatic islet cells damaged
• Body can’t make insulin• Blood sugar remains high• Damage to blood vessels, other tissues
• Stem cells to the rescue?– Replace insulin-producing cells
Treatments
• Insulin injection– pain, inconvenience, expense– Lack of ‘natural’ regulation of
insulin levels
• Islet cell transplantation– From cadavers’ pancreases– Works well (~300 trials)– Shortage of pancreases
Embryonic stem cells?
• ES cells: good at proliferation– Overcome the shortage problem
• But can they be induced to specialize properly?
Dr. Ron McKay, NIH
• Induced mouse ES cells to form islet cells– At least cells that look like islet
cells
• Seem to behave like islet cells when injected into mice
What about humans?
• Can human ES cells be differentiated appropriately?– Right ‘cocktail’ of factors
• Lab at University of Florida (Bryon Petersen)– Made insulin-producing cells– Cured diabetic mice for ~ three weeks– Teratoma formation
Parkinson’s disease
• Motor disorder– Tremor– Slow movement, Rigidity– Poor balance
Degeneration of brain cells
• Cells in the substantia nigra
• Loss of the chemical dopamine
• No clear reason why
Treatments
• Several drugs– Mimic dopamine OR enhance the effect of
what little dopamine is left– L-dopa
• Transplantation– No positive results yet
Stem cells to the rescue?
• Harvard study:– Rats with “Parkinson’s disease”– Injected healthy ES cells– Cells began producing dopamine– Motor function improvement– 20% formed brain teratomas
Stem Cell Targets
• Degenerative diseases (or pseudo-degenerative: see leukemia)
• Chronic diseases
• Discrete/defined tissues
AIDS?