Human stem cells The 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 erythrocytes

Autoimmune diseases

 Systemic lupus erythematosus Reconstitute immune system

 Crohn disease Reconstitute immune system

Immune def iciency disorders

 Severe combined immune def iciency Gene correction in immune cells

 Wiscott-A ldrich Gene correction in immune cells

Cardiovascular diseases

 Myocardial ischemia Replace ischemic cardiomyocytes

Hepatic disease

 Hepatic failure Replace or regenerate hepatocytes

Metabolic disorders

 Diabetes Replace pancreatic islets or induce beta cell dif ferentiation

 Osteoporosis Regenerate bone

 Gaucher disease Express glucocerebrosidase in macrophages

Musculoskeletal disorders

 Duchenne muscular dystrophy Replace myoblasts

Neurologic 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 species Homo 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 Blastocysts That are Rendered Incapable of Full Development

“Not an embryo”or

a diseased embryo?

Copyright ©2006 AlphaMed Press

Gruen, 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.”