Stem Cells: Getting Informed!

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Contents OVERVIEW What is a stem cell? Key terms A short history Two types of stem cells The pro and con arguments Final comments GLOSSARY USEFUL LINKS USEFUL LITERATURE CITED LITERATURE AND LINKS Web Literacy project by Greta Jones Dalhousie University April, 2002

Rat adult stem cells; image courtesy of Dr. Ivar Mendez, Dalhousie University

There has been much debate over the use of human embryonic stem cells. On the one hand, their potential use for the cure of diseases in the near future is quite promising. Others say that no cure can justify destroying a human embryo. This webpage provides an overview of the debate and some relevant background. Useful links and literature provide a gateway to further pursue the topic.

Terms highlighted in blue are defined in the glossary.

Key terms
(Sources *STEM CELLS: A PRIMER; *STEM CELLS: NIH)

Many of the terms used to define and qualify the properties of stem cells depend on their behavior "in vivo" (in the living organism). The terms totipotent, pluripotent, and unipotent are key terms describing the in vivo potential of stem cells.

Totipotent refers to the fertilized egg or zygote; it has the potential to generate all cells and tissues that make up the embryo and all other extra embryonic membranes and tissues which support "in utero" (in the uterus) development.

Pluripotent is used to describe stem cells that can give rise to cells in all three germ layers (endoderm, mesoderm, and ectoderm). These pluripotent stem cells have the potential to differentiate into any type of cell that would make up the adult organism. Pluripotency is observed in the natural course of embryonic development and under certain laboratory conditions. For example, the embronic germ layer, endoderm will differentiate into the thyroid, lung, liver, pancreas, and other tissues.

Unipotent stem cells are capable of differentiating along only one cell type lineage. For example, undamaged cells of a specific tissue are qualified as unipotent cells. If the tissue becomes damaged and only one cell type is required, the cells would undergo self-replication to repair the tissue. However, if repairing the tissue required more than one cell type then pluripotent stem cells would have to be activated.

In the mid 1960's, R. G. Edwards and colleagues at Cambridge University began studying differentiation in rabbit embryonic cells in vitro. These cells were obtained from the inner cell mass of the rabbit embryo. The resulting properties of cell lines from the pre- implantation blastocyst were quite surprising. They yielded specific types of cells such as connective tissue, muscle, neurons, and blood islands. The cell lines had long lifespans and were quite stable.

Some Key Events 1963- Rabbit stem cells established in culture 1984- First attempt at producing human stem cells 1986- Mouse embryonic stem cells repopulate and repair damaged haematopoietic system 1998- Stem cells from human embryos isolated and grown in the laboratory.

Richard Gardner, a graduate student of R. G. Edwards, furthered the work by inserting cells from the aforementioned experiment in mice blastocoel to produce a specific coat colour.... " its typical coat- colour pattern becoming the instantly recognized symbol for transgenic mice" ( Edwards, 2001). Embryonic stem cells became a familiar term at Cambridge University and the potential of these cells was beginning to be realized.

Rare human blastocysts became available from IVF procedures in R. G. Edwards' laboratory , in the early 1980s. This enabled him to attempt to produce human stem cells, but the worked ended because of an ethical decision made on the use of human embryos. In 1986, Peter Hollands, another graduate student of Edwards, demonstrated that mouse embryonic stem cells could colonize and repair damaged tissues in the haematopoietic system in adult mice.

James Thomson and colleagues at the University of Wisconsin isolated and grew embryonic stem cells from humans in 1998. At John Hopkins University, John Gearhart isolated human germ cells. In 1999 and 2000, researchers manipulated cells from adult mouse tissues. For example, they observed that bone marrow cells could be turned into nerve or liver cells and that stem cells found in the brain could form other kinds of cells.

CHARACTERISTICS AND APPLICATIONS OF EMBRYONIC AND ADULT STEM CELLS. ( Sources *NIH: STEM CELLS: A PRIMER; *STEM CELLS: NIH)

Stem Cell Type	Description	Future Medical Application
embryonic stem (ES) cells	ES cells are undifferentiated cells derived from the inner cell mass of the blastocyst. They are the original cells of our body tissues ES cells have the potential to become over 200 specialized (mature) cell types. They are pluripotent. (Source *STEM CELLS: NIH)	Many diseases arise because of death or dysfunction of a cell. Scientists believe that when healthy tissue-specific cells are introduced the function of tissues can be restored. Effective treatment for Alzheimer's, Diabetes, heart disease, and Parkinson's may be a near future reality.
adult (AS) stem cells	AS are cells undifferentiated (unspecialized) cells that are found in adult tissues. They can be replicated and become all of the specialized cells of tissues from which they originated. Sources of adult stem cells are found in bone marrow, blood stream, liver, skin, gastrointestinal tract, and other tissues. No adult stem cells have been isolated that can form all cell types of the body.	AS cells may provide cures for diseases by organ function restoration. There would be no immunological issues because cells would come from the same individual who has the malfunction in question.

Issue 1

The Pro side: Alleviating human suffering and curing diseases are more than honorable reasons for the use of (ES) cells. Many scientists and other advocates believe that embryonic stem cell research would pave the way in the near future for effective treatment for many diseases. They believe that when new healthy tissue specific cells are introduced, the function of the damaged tissue can be restored. This would give hope and alleviate human suffering. They believe that morally they have the right to find medical cures and solutions to help people as soon as possible.

The Con side: While relieving suffering and saving lives is commendable, not all methods used to attain this goal are morally or ethically right.

Issue 2

The Pro side: Scientists realize that the destruction of human embryos is not without cost but put more emphasis on saving and improving lives. Scientists generally accept that human development begins at the stage of fertilization and formation of an embryo; embryos are worthy of respect and they know that destroying them is morally costly. However, they put greater value on improving and saving lives of children and adults.(LASKER FOUNDATION, 2001)

The Con side: Human embryos are not tissues or a group of cells but the smallest of individuals and should be protected and have the same rights as other human beings. To obtain embryonic stem cells human embryos have to be destroyed. Human embryos have the right to have the same respect and rights as other human beings. They have the right to be protected, particularly because they are very vulnerable. The U.S. has put into place laws to affirm its stand on the dignity of every human being. Many States in the U.S. have laws that protect human embryos from harmful experimentation.

Issue 3

The Pro side: The embryos used are left over from in vitro fertilization procedures and from aborted fetuses. After parents have chosen a specific embryo to implant in utero, the other embryos, with the parents permission, are preserved for future research. Using these embryos will help others have a better life and this is a worthy goal.

The Con side: Those who oppose this type of experimentation say that human beings unable to give consent to scientific experimentation should not be subjects to those experiments. They realize that opposition to embryonic stem cell research is at a moral cost. It will retard medical advances delay alleviating great suffering.

Issue 4

The Pro side: Embryonic stem cells will provide a greater potential for the cure of diseases than adult stem cells and other methods.
Embryonic stem (ES) cells have a greater range of differentiation patterns. The quantities of stem cells needed to perform tissue repair are easily obtained from (ES) cells. In contrast, adult stem cells are not easy to isolate and quantities are limited. There is also less rejection of tissue with fetal embryonic stem cells.

The Con side: In the past , it was thought that adult stem cells were not as versatile as (ES) cells. There appears to be new evidence to suggest otherwise. An investigation was conducted of patients who had received blood stem cell transfusion to rebuild bone marrow after cancer treatment. These patients were found to have transfusion source cells in their liver and skin.(LETS BE ADULTS ABOUT STEM CELL RESEARCH, 2002) There are also other sources of stem cells, stem cells from placenta and umbilical cord blood in live births.

In the summer of 2001, President George W. Bush made decisions on this subject that seemed like an intelligent compromise. However, R.G Edward's made this statement, " It is ironic that in the United States today, President George W. Bush and the National Institutes of Health object ethically to using human embryos to make stem cells, yet accept 64 cell lines prepared by foreign investigators or by private US clinics."(R. G. Edwards,2001)

In Canada, the federal government allows government- funded scientists to use left over human embryos from abortions and in vitro fertilization procedures. This gives the Canadian researchers access to new human embryos, unlike their American counterparts who only have access to existing cell lines.

The intent of this webpage was to inform and open your eyes to the complexity of the ethical issues surrounding in stem cell research. Hopefully this goal was accomplished.

Adult stem cell

An undifferentiated cell found in a differentiated tissue that can renew itself and (with certain limitations) differentiate to yield all the specialized cell types of the tissue from which it originated. (*NIH: STEM CELLS: A PRIMER)

blastocyst

The blastocyst consists of 30-150 cells, at this stage the embryo has not been implanted in the uterine wall.(*STEM CELLS: NIH)

bone marrow

The soft, lining tissue that fills most bone cavities. It consists of haematopoietic stem cells that produce red and white blood cells. The bone marrow also contains mesenchymal stem cells that a number of cell types come from, including chondrocytes. (*STEM CELLS: NIH)

differentiate

The process by which an unspecialized cell in early development obtains the characteristics of a specialized cell (for example, a heart, a spleen, or a muscle cell).

Embryonic stem (ES) cells

Primitive (undifferentiated) cells from the embryo that have the potential to become a wide variety of specialized cell types. (*STEM CELLS: NIH)

haematopoietic

Cells from which all red and white blood cells come from. (*NIH: STEM CELLS: A PRIMER)

inner cell mass

The cluster of cells inside the blastocyst. These cells give rise to the fetus, the developing human being. (*STEM CELLS: NIH)

in vitro

Literally, it means "in glass", in a test tube under laboratory conditions. (*NIH: STEM CELLS: A PRIMER)

in vitro fertilization (IVF)

An assisted reproduction method in which fertilization is accomplished in laboratory conditions. i.e., outside of the body. (*STEM CELLS: NIH)

pluripotent

"Pluri" meaning "many or several", cells that give rise to cells derived from all three germ layers. (*NIH: STEM CELLS: A PRIMER)

totipotent

"Toti" meaning "entire", cells of a very early embryo with the capability to differentiate into all tissues and organs. (*NIH: STEM CELLS: A PRIMER)

unipotent

"Uni" meaning "one", cells in study are able to differentiate only along one lineage.
(*NIH: STEM CELLS: A PRIMER)

• CANADA ISSUES GUIDELINES FOR STEM CELL RESEARCH
  (http://www.nandotimes.com/healthscience/story/283699p-2547491c.html) The Nando Times, spons. (Mar. 2002, Viewed 05 Mar. 2002)
  A newspaper article which expresses the government of Canada's latest stand on stem cell research. On March 5, 2002, the government banned human embryo cloning but is allowing government funded scientists to use embryos from IVF procedures and aborted fetuses.
• ELIZABETH COHEN: ETHICS OF STEM CELL RESEARCH
  (http://www.cnn.com/2001/HEALTH/07/17/cohen.otsc/) CNN.com/HEALTH, spons. (July 2001, Viewed 15 Feb. 2002)
  Elizabeth Cohen is a CNN medical correspondent based in Atlanta, GA. She reports on both sides of the stem cell debate. She informs us on how uninformed people are about what stem cells really are.
• LASKER FOUNDATION
  Lasker Medical Research Network, spons. (2001, Viewed 24 April. 2002)
  (http://www.laskerfoundation.org/news/stemcell/stemcell.html)
  This site gives information on stem cell research and its history. It documents future implications and profiles scientists who have contributed to stem cell research. It also provides quotes and leading opinions in this field.
• LET'S BE ADULTS ABOUT STEM CELL RESEARCH
  (http://www.nationalpost.com/commentary/story.html?f=/stories/20020311/298825.html) National Post Online, spons. (Mar. 2002, Viewed 28 Mar. 2002)
  A news article that gives an update on Stem cell Research.
  There is promising news about isolating adult stem cells from patients
  for repair of diseased tissue. http://www.cnn.com/2001/HEALTH/07/17/cohen.otsc/
• STEM CELLS: A PRIMER
  (http://www.nih.gov/news/stemcell/primer.htm) National Institutes of Health, spons. (May 2000, Viewed 15 Feb. 2002)
  This site gives information on the different types of stem cells and their importance to medicine and health care. Definitions and properties of stem cells are presented along with other pertinent information.
• STEM CELLS: NIH
  (http://www.nih.gov/news/stemcell/scireport.htm) National Institutes of Health, spons. (August 2001, Viewed 15 Feb. 2002)
  A pdf document that provides detailed information on embryonic, adult, and haematopoietic stem cells. There are chapters on what effect the use of stem cells might have on autoimmune diseases, diabetes, and repairing the damaged heart.

• Abkowltz, J.L. 2002. Can human hematopoietic stem cells become skin, gut, or liver cells? New England Journal of Medicine 346(10): 770-772. http://www.library.dal.ca/ejournals/restrict/nejm.html
• Abrams, E. et al. 1999. On Human Embryos and Stem Cell Research: An Appeal for Legally and Ethically Responsible Science and Public Policy , spons. The Center for Bioethics and Human Dignity. http://www.stemcellresearch.org/statement/statement.htm
• Adam, D. 2002. Britain banks on embryonic stem cells to gain competitive edge. Nature 416(6876): 3-4.
• Edwards, R.G. 2001. IVF and the history of stem cells Nature 413: 449-351.
• Thomson, J. et al. 1998. Embryonic stem cell lines derived from human blastocysts. Science 282: 1145-1147. (7 authors)

• CANADA ISSUES GUIDELINES FOR STEM CELL RESEARCH
  (http://www.nandotimes.com/healthscience/story/283699p-2547491c.html) The Nando Times, spons. (Mar. 2002, Viewed 05 Mar. 2002)
  
• ELIZABETH COHEN: ETHICS OF STEM CELL RESEARCH
  (http://www.cnn.com/2001/HEALTH/07/17/cohen.otsc/) CNN.com/HEALTH, spons. (July 2001, Viewed 15 Feb. 2002)
  
• LASKER FOUNDATION
  Lasker Medical Research Network, spons. (2001, Veiwed 24 April. 2002)
  (http://www.laskerfoundation.org/news/stemcell/stemcell.html)
• LET'S BE ADULTS ABOUT STEM CELL RESEARCH
  (http://www.nationalpost.com/commentary/story.html?f=/stories/20020311/298825.html) National Post Online, spons. (Mar. 2002, Viewed 28 Mar. 2002)
  
• STEM CELLS: A PRIMER
  (http://www.nih.gov/news/stemcell/primer.htm) National Institutes of Health, spons. (May 2000, Viewed 15 Feb. 2002)
  
• STEM CELLS: NIH
  (http://www.nih.gov/news/stemcell/scireport.htm) National Institutes of Health, spons. (Aug. 2001, Viewed 15 Feb. 2002)
  
• Abkowltz J.L. 2002. Can human hematopoietic stem cells become skin, gut, or liver cells? New England Journal of Medicine 346(10): 770-772. http://www.library.dal.ca/ejournals/restrict/nejm.html
• Abrams, E. et al. 1999. On Human Embryos and Stem Cell Research: An Appeal for Legally and Ethically Responsible Science and Public Policy , spons. The Center for Bioethics and Human Dignity. http://www.stemcellresearch.org/statement/statement.htm
• Adam, D. 2002. Britain banks on embryonic stem cells to gain competitive edge. Nature 416(6876): 3-4.
• Edwards, R.G. 2001. IVF and the history of stem cells. Nature 413: 449-351.
• Thomson, J. et al. 1998. Embryonic stem cell lines derived from human blastocysts. Science 282: 1145-1147.