Human stem cells The perspective of a Catholic physician-scientist

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Human stem cells The perspective of a Catholic physician-scientist Jose C. Florez MD, PhD Massachusetts 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 are stem cells?

Stages of development Wobus, A. M. et al. Physiol. Rev. 85: 635-678 2005 Copyright 2005 American Physiological Society

Stem cells can become different tissues Copyright 2005 American Physiological Society Wobus, A. M. et al. Physiol. Rev. 85: 635-678 2005

The promise Mayhall, Paffett-Lugassy and Zon, Curr Opinion Cell Biol 16 (2004) 713-720

Disease Potential Applications of Stem Cell Therapy Hematologic disorders Leukemias Multiple myeloma Sickle cell anemia Autoimmune diseases Systemic lupus erythematosus Crohn disease Immune deficiency disorders Severe combined immune deficiency Wiscott-Aldrich Cardiovascular diseases Myocardial ischemia Hepatic disease Hepatic failure Metabolic disorders Diabetes Osteoporosis Gaucher disease Musculoskeletal disorders Duchenne muscular dystrophy Neurologic disorders Parkinson's disease Stem Cell Therapy Goal Replace marrow ; graft vs tumor Replace marrow ; graft vs tumor Replace or correct erythrocytes Reconstitute immune system Reconstitute immune system Gene correction in immune cells Gene correction in immune cells Replace ischemic cardiomyocytes Replace or regenerate hepatocytes Replace pancreatic islets or induce beta cell differentiation Regenerate bone Express glucocerebrosidase in macrophages Replace myoblasts Replace dopamine-producing neurons

Adult stem cells

[Adapted from NIH Guide on Stem Cells: Scientific Promise and Future, 2001 Terese Winslow medical illustrator 2001, Terese Winslow.]

Possible Roles of Adult Stem Cells in Tissue Repair Korbling, M. et al. N Engl J Med 2003;349:570-582

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

From an embryo From a fetus Wobus, A. M. et al. Physiol. Rev. 85: 635-678 2005 Copyright 2005 American Physiological Society

How do you get an embryo? Korbling, M. et al. N Engl J Med 2003;349:570-582

You can make one through human cloning (aka nuclear transfer) Mayhall, Paffett-Lugassy and Zon, Curr Opinion Cell Biol 16 (2004) 713-720

Retrieval of Oocytes Steinbrook, R. N Engl J Med 2006;354:324-326

Somatic-Cell Nuclear Transfer Snyder, E. Y. et al. N Engl J Med 2006;354:321-324

Human cloning Human cloning generates a much younger copy of oneself Usually defective But viable Wobus, A. M. et al. Physiol. Rev. 85: 635-678 2005 Copyright 2005 American Physiological Society

Reproductive Cloning and Therapeutic Cloning Hochedlinger, K. et al. N Engl J Med 2003;349:275-286

Is reproductive cloning possible? Dolly the sheep

Reproductive cloning generates defective adults: most scientists agree on moratorium Hochedlinger, K. et al. N Engl J Med 2003;349:275-286

The problem To harvest embryonic stem cells, the embryo must be destroyed Landry and Zucker, J. Clin. Invest. 114:1184-1186 (2004)

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 frozen and are going to die anyway So are people on death row Should we take their organs?

A ray of hope: Scientists attempts to remain within ethical boundaries Derivation of Mouse Embryonic Stem Cells from an Eight-Cell Embryo Defective? Harvesting? Embryo? Solter, D. N Engl J Med 2005;353:2321-2323

It has recently been done to human embryos (in our own back yard) Human embryonic stem cell lines derived from single blastomeres Irina Klimanskaya, Young Chung, Sandy Becker, Shi-Jiang Lu and Robert Lanza Nature, doi:10.1038/nature05142

Derivation of Mouse Embryonic Stem Cells from Blastocysts That are Rendered Incapable of Full Development Not an embryo or a diseased embryo? Solter, D. N Engl J Med 2005;353:2321-2323

Summary of approaches to generate human embryonic stem cells Copyright 2006 AlphaMed Press Gruen, L. et al. Stem Cells 006;24:2162-2169

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.