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Stem Cell Research: Harnessing Potential for Medical Breakthroughs

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Stem cell research offers groundbreaking possibilities for treating various medical conditions. Stem cells can regenerate lost or damaged tissues, making them vital in treating spinal cord injuries, burns, and degenerative diseases such as diabetes and Parkinson’s. By isolating potent stem cells, we can coax them into becoming specialized cells needed for healing. Although challenges exist, including graft-versus-host disease, advancements in factor- and niche-directed differentiation techniques hold immense promise. As research continues, the future of stem cell therapies seems increasingly hopeful.

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Stem Cell Research: Harnessing Potential for Medical Breakthroughs

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  1. WHY stem cell research? Potential medical applications

  2. Stem cells produce new cells • Adult: replace damaged/lost cells • Embryonic: build the organism Can this power be harnessed to produce new cells artificially?

  3. 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?

  4. 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

  5. Cells ‘home in’ on the site of injury Cultured stem cells in the lab DELIVER (inject/transplant) the cultured SC One way: ‘Niche’-directed differentiation DAMAGED TISSUE HEALTHY TISSUE Peer pressure: Neighbors cause SC to differentiate appropriately

  6. 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

  7. Production of blood cells occurs in the bone marrow

  8. (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

  9. 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

  10. Another way: Factor-directed differentiation DAMAGED TISSUE HEALTHY TISSUE Cells heal the damage Allow cells to differentiate appropriately Add a chemical factor to induce differentiation Culture stem cells in the lab DELIVER (inject/transplant) the differentiated cells

  11. Factor-directed differentiation • Retinoic acid + insulin: fat cells • Retinoic acid: nervous system • Retinoic acid + DMSO: muscle cells • Interleukin-3: neurons, white blood cells

  12. 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)

  13. 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?

  14. Niche- vs. factor-directed differentiation • Ultimate answer: hybrid between the two?

  15. Paralysis (spinal cord injuries) • Juvenile diabetes • Parkinson’s

  16. 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?

  17. Dr. Hans Keirstead • Use of human embryonic stem cells to ‘cure’ paralyzed rats • Partially differentiate in culture (factor-directed) • Inject into the spinal cord

  18. http://www.hopkinsmedicine.org/Press_releases/2006/images/video1.wmvhttp://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

  19. Trials in humans ‘soon’…one to two years? • Need to convince FDA that it’s safe enough…and ethically responsible

  20. 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

  21. 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”

  22. 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

  23. 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

  24. Embryonic stem cells? • ES cells: good at proliferation • Overcome the shortage problem • But can they be induced to specialize properly?

  25. 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

  26. 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

  27. Parkinson’s disease • Motor disorder • Tremor • Slow movement, Rigidity • Poor balance

  28. Cells in the substantia nigra Loss of the chemical dopamine No clear reason why Degeneration of brain cells

  29. Treatments • Several drugs • Mimic dopamine OR enhance the effect of what little dopamine is left • L-dopa • Transplantation • No positive results yet

  30. 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

  31. Stem Cell Targets • Degenerative diseases (or pseudo-degenerative: see leukemia) • Chronic diseases • Discrete/defined tissues AIDS?

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