Stem Cells and Diabetes: A Website for BI108 - PowerPoint PPT Presentation

Loading...

PPT – Stem Cells and Diabetes: A Website for BI108 PowerPoint presentation | free to download - id: 3d2dbd-ODg2N



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

Stem Cells and Diabetes: A Website for BI108

Description:

Stem Cells and Diabetes: A Website for BI108 David Keyzer Nicholas Marcantonio Lesley Rabach Morgan Rabach Sannon Watkins Diabetes Diabetes is a syndrome ... – PowerPoint PPT presentation

Number of Views:98
Avg rating:3.0/5.0
Slides: 25
Provided by: biomedBro3
Learn more at: http://biomed.brown.edu
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Stem Cells and Diabetes: A Website for BI108


1
Stem Cells and DiabetesA Website for BI108
  • David Keyzer
  • Nicholas Marcantonio
  • Lesley Rabach
  • Morgan Rabach
  • Sannon Watkins

2
Diabetes
  • Diabetes is a syndrome characterized by
    hyperglycemia and glucose intolerance.
  • This is due to either insulin deficiency or
    impaired effectiveness of insulin action.
  • There are two main classes of diabetes
  • Class I-juevenile diabetes, arises due to
    autoimmune destruction of pancreatic beta cells
    that secrete insulin
  • Class II-adult onset diabetes, arises due to
    insufficient insulin production. Symptoms can
    often be controlled by exercise and dietary
    restriction.
  • Stem cell therapies hold promise for the
    treatment of both classes.

3
Significant Risks are associated with Diabetes
  • Heart disease/High blood pressure
  • -Diabetics die from heart disease 2 to 4
    times as often as diabetes free adults.
  • -60 to 65 of people with diabetes have
    high blood pressure
  • Stroke
  • -The risk of stroke is 2 to 4 X higher in
    diabetic people.
  • Blindness
  • -Diabetes is the leading cause of new
    blindness in adults ages 20 to 74.
  • Kidney disease
  • -Diabetes is the leading cause of end-stage
    renal disease (ESRD).  It accounts for 40 of
    new cases.
  • -In 1995, approximately 100,000 diabetic
    people underwent dialysis or kidney
    transplantation.
  • Amputations
  • - More than 50 of lower limb amputations in
    the United States result from diabetes related 
    problems.

4
Diabetes Impact on Society
  • About 16 million people (5.9 of the population)
    in the United States have diabetes mellitus.
  • Diabetes is one of the leading causes of death
    and disability. It was listed as the 7th leading
    cause of death in the US by the CDC in 1996.
  • Diabetes costs about 98 billion per year 1.
  • The incidence of diabetes is rapidly on the rise

Source Journal of the American Medical
Association
5
Economics
  • Of the 98.2 Billion Spent, 52.4 Billion Were
    Spent on Complications of Diabetes. This
    Accounts for Over 5 of the US Healthcare Budget.
  • The Average Cost of Treating Diabetes in the
    United States is 3,400 per Patient per Year
  • 170,000 After 50 years

6
Am I Covered?

  • Most States Require That Insurance Companies
    Cover Diabetes Treatment to Some Degree
  • The Patient Still Shoulders A Significant Burden,
    Often Paying A Percentage

7
Current Treatment?Stem Cells and the FUTURE
  • Dietary adjustments and exercise is sufficient
    therapy for milder symptoms
  • Insulin Therapy is the most popular current
    treatment for diabetes
  • It is an insufficient therapy. It does not allow
    for effective adaptation to changing levels of
    blood glucose
  • It is an inconvenience. It requires frequent
    injections/ the presence of a pump
  • Stem cell therapies, if successful, offer a
    better life for diabetes sufferers
  • No need for multiple injections and pumps
  • More responsive to changing blood glucose levels

8
Stem Cells-Potential Therapy for Diabetes
  • Cells that have the capacity to regenerate
    themselves for long periods of time, and
    differentiate into specific tissues
  • Two main sources of stem cells
  • Adult-from adult tissues
  • Embryonic- from early embryos
  • Have the potential to treat diabetes and many
    other diseases(detail coming later)
  • However, complications include
  • Maintaining in cell lines in culture
  • Immune rejection
  • Teratoma formation (ES)
  • Difficulties in identifying and isolating,
    scarcity (Adult SC)
  • Ethical Issues (ES)

9
Whole Pancreas Transplants
  • 1,300 people with type 1 diabetes receive
    whole-organ pancreas transplants each year
  • 83 percent of these patients have no symptoms of
    diabetes and do not have to take insulin to
    maintain normal glucose concentrations in the
    blood. 2
  • However, two obstacles prevent transplantation
    from becoming a wide-spread therapy for type 1
    diabetes
  • Shortage of donor supply
  • Need for Immunosuppressive therapy

10
Islet Cell Transplantation
  • Potential alternative for whole-organ transplants
  • Non-invasive
  • Less expensive
  • Less morbidity
  • Enticing, because, if islets can be cultured and
    replicated in vitro, the donor supply can be
    greatly increased
  • But, similar to whole-organ transplants in that
    immunosuppression would still be needed

Source http//cellbio.utmb.edu/microanatomy/Endoc
rines/endocrines.htm
11
Edmonton Protocol
  • "Less than 10 of the almost 300 islet allografts
    transplanted since 1990 resulted in insulin
    independence for periods of more than 12 months"
    3.
  • But in 2000, researchers reported a series of
    successful transplants according to the Edmonton
    protocol 4
  • No cyclosporine, azathioprine, or steroids
  • Instead, sirolimus, tacrolimus, and daclizumab
  • About twice as many islets transplanted as
    compared to earlier protocols

12
Results of Edmonton Protocol
  • All patients have been resolved of unstable type
    1 diabetes and now have no problems with wide
    swings of blood glucose or hypoglycemia 5
  • Problems include
  • Lowered white cell count
  • Hemorrhage
  • Immunosuppression
  • SHORTAGE OF DONOR CELLS!!!
  • Long term effects need to be evaluated, but,
    demonstrates that islets can be transplanted such
    that they maintain sensitivity to glucose, and
    continue to secrete insulin

Source 4
13
The Promise of Stem Cells
  • Edmonton protocol shows that cell-based therapies
    may serve as viable alternative to whole-organ
    transplant.
  • And, in the longer term, perhaps insulin therapy
  • But, for cell-based therapies to become
    clinically applicable
  • Donor supply needs to be increased
  • Issues regarding immunosuppression must be
    resolved
  • Stem cells offer the best way to tackle these
    issues

14
Cell Populations
  • It is currently unclear whether treatment would
    be beneficial with just beta cells or with
    complete pancreatic islets
  • Islets contain alpha, beta, and delta cells
  • Current research indicates that beta cells are
    less responsive to changes in glucose
    concentration than complete pancreatic islets.
  • Many researchers believe that a system in which
    the stem cells will become complete islet cluster
    will prove most beneficial.

15
Increasing Donor Supply?
  • Fetal Tissue
  • Already differentiated
  • No need for upstream specification
  • However
  • Small donor supply, ethical issues, difficult to
    culture
  • Adult Tissue
  • Harvested from cadavers, cells lining pancreatic
    ducts, cells in pancreatic tissue
  • Isolated patient-specific
  • No ethical concerns
  • Greater tissue supply
  • But, difficulty with proliferating and culturing
    already differentiated beta cells from all
    cadaver/live patient tissue

16
Increasing Donor Supply II
  • Embryonic Stem Cells
  • Multipotent
  • Limitless capacity to replicate
  • Easiest to genetically manipulate
  • Embryoid bodies contain a subset of cells that
    function like beta cells.
  • Implantation may lead to teratoma formation
  • But, ethical concerns.


Source http//www.time.com/time/2001/stemcells/
17
Graft Rejection/Immunology
  • Ultimate goal create a line of donor cells that
    can be transplanted to diabetic patients that
    will not be destroyed by a recipients immune
    system
  • Thus, patients would not require
    immunosuppressive drugs
  • But, these cells must evade rejection for being
    non-self, as well as autoimmune antibodies
  • Research has shown that patients who receive
    pancreas transplants generate anti-islet
    antibodies to allogeneic islet cells

18
Graft Rejection/Immunology 2
  • Immunoisolation
  • Encapsulation must
  • allow uptake oxygen and other nutrients
  • allow bi-directional flow of glucose and insulin
  • Biocompatible 6. 
  • Problems caused by
  • Difficult diffusion kinetics
  • Issues with mechanical stability
  • Genetic Engineering?
  • Removing/Matching HLA antigens
  • Automimmunity?

Source 7
19
A Word On Ethics
  • Patients Urge Research
  • Potentiality What Constitutes A Person?
  • Government Funding Limited
  • President Limits Research on Embryonic Stem
    Cells
  • Past Precedents
  • Where to Draw the Line?

Source http//www.specialchildren.about.com/libra
ry/weekly/aa073101b.htm
20
Interview with a Type I Diabetic
  • Insurance Case Example
  • Covers Part of the Insulin Pump Cost
  • 700 Deductible, then 80 of Treatment Cost
  • --------------------------------------------------
    ----------------
  • Given that a cure for diabetes were offered which
    entailed some level of risk, what level of risk
    would you consider acceptable?
  • I would be willing to take almost no risk. 
    Studies have shown a very strong correlation
    between control of blood glucose and the
    incidence of complications.  Because I control my
    diabetes very tightly, I am not at risk of any
    complications, at least not for a long time.

Type I Diabetic Age 21 Diagnosed 9 Years Ago
21
Interview (continued)
  • If a cure could be offered with little to no
    risk, what would you be willing to pay?
  • Well, I would have to think about the cumulative
    cost of my disease over my lifetime, as well as
    the punitive effects of having it.  It's hard to
    say.  At this stage of my life, this is a disease
    that I can live with, even though it's a hassle.
  • . . .
  • The sentiment in the diabetes community is that
    a cure could almost come any day now.  With all
    of the diabetics I know, the feeling is
    positive.
  • Bradley Naylor, Brown 03

22
Future Outlook
  • Ultimate goal
  • Unlimited supply of insulin-secreting cells that
    will not be destroyed via alloreactivity or
    auto-antibodies
  • In the meantime, expect stem cell research to
    lead to supply of donor cells that can be used in
    cell-based therapies
  • 1st Gen Islet transplantation with
    immunosuppressive drugs as replacement for
    whole-organ transplants, but not insulin therapy
  • Improved drugs(tolerance inducing drugs) may
    increase number of recipients
  • 2nd Gen? Encapsulated islets that do not require
    immunosuppressive drugs?
  • If this is viable, perhaps it will begin to
    replace insulin therapy
  • Type II Diabetes
  • New evidence suggests transplantation has benefits

23
Acknowledgements
  • Sincere thanks to Dr. E  Ed Baetge, Ph.D., the
    Chief Scientific Officer of CyThera Inc.  His
    knowledge, insight, and experience made our
    website possible.  Please take some time to visit
    www.cytheraco.com to learn about CyThera, and
    it's research of stem cells for use in the
    treatment of type 1 diabetes.

24
Works Cited
  • 1 http//www.cdc.gov/diabetes/pubs/facts98.htmt
    op
  • 2 National Institutes of Health (US) NIH.
    Stem Cells Scientific Progress and Future
    Research Directions. Bethesda (MD) NIH 2001
    Jun. Available from http//www.nih.gov/news/stemc
    ell/scireport.htm.
  • 3 Berná G, León-Quinto T, Enseñat-Waser R,
    Montanya E, Martín F, Soria B. Stem cells and
    diabetes. Biomedicine and Pharmacotherapy
    200155206-12.
  • 4 Shapiro AMJ, Lakey JRT, Ryan EA, Korbutt GS,
    Toth E, Warnock GL, Kneteman NM, Rajotte RV.
    Islet transplantation in seven patients with type
    1 diabetes mellitus using a glucocorticoid-free
    immunosuppressive regimen. The New England
    Journal of Medicine 2000343(4)230-8.
  • 5 Ryan EA, Lakey JRT, Rajotte RV, et al.
    Clinical outcomes and insulin secretion after
    islet transplantation with the Edmonton protocol.
    Diabetes 200150710-9.
  • 6 Berney T, Ricordi C. Islet cell
    transplantation the future? Langenbeck's Archive
    of Surgery 2000385373-8.
  • 7  Lembert N, Petersen P, Wesche J, et al. In
    vitro test of new biomaterials for the
    development of a bioartificial pancreas. Annals
    of the New York Academy of Sciences
    2001944271-6.
About PowerShow.com