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Human stem cellsThe perspective of a
Catholic physician-scientist
Jose C. Florez MD, PhDMassachusetts General Hospital
Harvard Medical School
Outline
• Intro on human development• What are stem cells?• What can stem cells be used for?• How do we obtain stem cells?• What is a human embryo?• How should we treat a human embryo?• Alternatives
Fertilization
Sperm & egg Embryo
The embryo’s journey
Implantation
What arestem cells?
Copyright ©2005 American Physiological Society
Wobus, A. M. et al. Physiol. Rev. 85: 635-678 2005
Stages of development
Copyright ©2005 American Physiological Society
Wobus, A. M. et al. Physiol. Rev. 85: 635-678 2005
Stem cells can become different tissues
Mayhall, Paffett-Lugassy and Zon, Curr Opinion Cell Biol 16 (2004) 713-720
The promise
Disease Stem Cell Therapy GoalHematologic disorders Leukemias Replace marrow ; graf t vs tumor Multiple myeloma Replace marrow ; graf t vs tumor Sickle cell anemia Replace or correct erythrocytesAutoimmune diseases Systemic lupus erythematosus Reconstitute immune system Crohn disease Reconstitute immune systemImmune def iciency disorders Severe combined immune def iciency Gene correction in immune cells Wiscott-Aldrich Gene correction in immune cellsCardiovascular diseases Myocardial ischemia Replace ischemic cardiomyocytesHepatic disease Hepatic failure Replace or regenerate hepatocytesMetabolic disorders Diabetes Replace pancreatic islets or induce beta cell
dif ferentiation Osteoporosis Regenerate bone Gaucher disease Express glucocerebrosidase in macrophagesMusculoskeletal disorders Duchenne muscular dystrophy Replace myoblastsNeurologic disorders Parkinson's disease Replace dopamine-producing neurons
Potential Applications of Stem Cell Therapy
Adultstem cells
[Adapted from NIH Guide on Stem Cells: Scientific Promise and Future, 2001 Terese Winslow–medical illustrator ©2001, Terese Winslow.]
Korbling, M. et al. N Engl J Med 2003;349:570-582
Possible Roles of Adult Stem Cells in Tissue Repair
Korbling, M. et al. N Engl J Med 2003;349:570-582
Just recently published
So where do we get stem cells from?
• From adult tissues• From the umbilical cord of newborns• From healthy fetuses• From embryos
Copyright ©2005 American Physiological Society
Wobus, A. M. et al. Physiol. Rev. 85: 635-678 2005
From an embryo… From a fetus…
Korbling, M. et al. N Engl J Med 2003;349:570-582
How do you get an embryo?
Mayhall, Paffett-Lugassy and Zon, Curr Opinion Cell Biol 16 (2004) 713-720
You can make onethrough human
cloning
(aka nuclear transfer)
Steinbrook, R. N Engl J Med 2006;354:324-326
Retrieval of Oocytes
Snyder, E. Y. et al. N Engl J Med 2006;354:321-324
Somatic-Cell Nuclear Transfer
Copyright ©2005 American Physiological Society
Wobus, A. M. et al. Physiol. Rev. 85: 635-678 2005
Human cloning
• Human cloning generates a much younger copy of oneself
• Usually defective
• But viable
Hochedlinger, K. et al. N Engl J Med 2003;349:275-286
Reproductive Cloning and Therapeutic Cloning
Is reproductive cloning possible?
Dolly the sheep
Hochedlinger, K. et al. N Engl J Med 2003;349:275-286
Reproductive cloning generates defective adults: most scientists agree on moratorium
Landry and Zucker, J. Clin. Invest. 114:1184-1186 (2004)
The problem
To harvest embryonic stem cells, the embryo must be destroyed
What is an embryo?
• It’s alive• It’s human• It’s an individual, separate and distinct from
the mother
• Therefore, he/she is a member of our speciesHomo sapiens
• We were all embryos once…
But it’s so small! Just a cell…
• Human beings are defined by what they are, not by what they can do
• Is a mentally retarded person less human?• Is a patient with a stroke or dementia less
human?• Humanity goes beyond skills and abilities• An enlightened society protects its weakest
members
How should we treat a living member of our species?
• We do not take an innocent person’s life• We do not perform surgery on another human
being without his/her consent• We do not force him/her to donate organs
But the benefits are so great…
• The end does not justify the means
• The intentions are good, the goal is good, the result is good; but if the action itself is bad, then the entire procedure is unethical
• We could save many people by forcing a single person to donate both kidneys, heart, liver, lungs, pancreas, corneas…
But the embryos are frozenand are going to die anyway…
• So are people on death row… Should we take their organs?
Solter, D. N Engl J Med 2005;353:2321-2323
Derivation of Mouse Embryonic Stem Cells from an Eight-Cell Embryo
A ray of hope: Scientists’ attempts to remain within ethical boundaries
Harvesting?
Defective?
Embryo?
It has recently been done to human embryos(in our own back yard)
Human embryonic stem cell lines derived from single blastomeresIrina Klimanskaya, Young Chung, Sandy Becker, Shi-Jiang Lu and Robert Lanza
Nature , doi:10.1038/nature05142
Solter, D. N Engl J Med 2005;353:2321-2323
Derivation of Mouse Embryonic Stem Cells from BlastocystsThat are Rendered Incapable of Full Development
“Not an embryo”or
a diseased embryo?
Copyright ©2006 AlphaMed PressGruen, L. et al. Stem Cells 006;24:2162-2169
Summary of approaches to generate human embryonic stem cells
Countries where embryonic stem cells are being harvested
When ethics and research part ways…
Dr. Woo-Suk Hwang
Alternatives
• Continue to advance therapeutic uses of adult stem cells
• Expand existing umbilical cord stem cell banks• Research ways to make adult stem cells more versatile• Research ways to create stem cells while bypassing the
embryo stage• Work with existing embryonic stem cell lines• Explore ways of making animal stem cells amenable to
implantation in humans
Conclusions
• The Church is not opposed to research; it’s opposed to unethical research
• We must protect the most vulnerable• There is no scientific argument that proves that
the embryo is not a live member of our species• There are ways to generate stem cells without
destroying human embryos• We must be kept informed• We must defend the culture of life
Thank you
“Do not wait for leaders; do it alone, person to person.”
“Do not wait for leaders; do it alone, person to person.”
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