Human Stem Cell Research (embryonic and somatic) 11/9/2018 Stem Cells Human Stem Cell Research (embryonic and somatic)

What are Embryonic Stem Cells? 11/9/2018 What are Embryonic Stem Cells? They’re the blastomeres in the blastocyst… Zona pellucida Blastomeres (Zygote)

11/9/2018 Blastocyst Reached after four to six days (“hatches” from the zona pellicuda) Lasts approximately until the implantation in the uterus Upon implantation, a hormone (hCG) “notifies” the mother's body that she is pregnant, preventing menstruation Little later, leads to gastrulation (approx. two weeks or so later) Gastrulation is the start of the restricted (biological) definition of embryo http://www.nhmrc.gov.au/embryos/information/_files/humanembryo.pdf

Mammalian (Human) Embryogenesis – What is an embryo? 11/9/2018 Mammalian (Human) Embryogenesis – What is an embryo? The embryo of a placental mammal is defined as the organism between the first division of the zygote (a fertilized ovum) and the time until it becomes a fetus. In humans, the embryo is defined as the product of conception from implantation in the uterus through the eighth week of development. An embryo is called a fetus at a more advanced stage of development and up until birth or hatching. In humans, this is from the eighth week of gestation.

11/9/2018 NIH Definitions Stem cells - have the ability to divide for indefinite periods in culture and to give rise to specialized cells. Stem cells are cells that divide by mitosis to form either: two stem cells, thus increasing the size of the stem cell "pool", Or one daughter that goes on to differentiate, and one daughter that retains its stem-cell properties. Pluripotent Stem Cells - capable of giving rise to most tissues of an organism. Multipotent Stem Cells – capable of giving rise to cells that have a particular function. Totipotent Cells - have the capacity to form an entire organism (e.g., the fertilized egg). First four or so cells produced by cleavage of the fertilized egg are also totipotent. Cannot make more of themselves in mammals (no mammalian totipotent stem cells). Totipotent cells have the capacity to specialize into extraembryonic membranes and tissues, the embryo, and all postembryonic tissues and organs.

Totipotent vs. Pluripotent Stem Cells 11/9/2018 Multipotent Stem Cells

Embryonic Stem Cell vs Embryonic Germ Cell lines 11/9/2018 Embryonic Stem Cell vs Embryonic Germ Cell lines Embryonic Stem Cells From In-Vitro Fertilized embryos Embryonic Germ Cells From Aborted Fetuses

What are Embryonic Stem Cells? 11/9/2018 What are Embryonic Stem Cells? (Embryonic Stem Cells)

Start with the Animal Embryo 11/9/2018 Start with the Animal Embryo

Sources of Embryonic Stem cells 11/9/2018 Sources of Embryonic Stem cells Embryonic Stem cell lines Excess embryos from In-Vitro Fertilization clinics Embryos created for research by IVF Therapeutic cloning:  Because ES cells are pluripotent and easier to harvest than AS cells, most medical stem cell research is focused on ES cells. There are 4 known sources of ES cells.  ES cell lines - ES cells that have been kept alive in culture and encouraged to divide. There are about 100 such lines in existence around the world. Batches of cells can be removed from this cell line and used for research without destroying the cell line.  Excess embryos from IVF clinics. In vitro fertilization is a method of assisted reproduction. For couples that cannot have children, egg and sperm are united outside the body. The resulting embryo is implanted in the woman’s uterus, where it develops into a baby. This procedure sometimes results in the creation of excess embryos that are not implanted. The excess embryos are frozen for future use or discarded, and can be used as a source of ES cells.  Embryos created for research through IVF. Theoretically, embryos could be created through IVF for research. The embryos would be destroyed in the process of harvesting their ES cells.  Therapeutic cloning. This is a method of obtaining ES cells from someone who has already been born. These stem cells can be used to treat the individual without generating an immune response. (The human body recognizes and attacks foreign cells, including stem cells. This is a serious barrier to stem cell therapy.)  The process of therapeutic cloning is shown in this diagram. It begins by taking a somatic (body) cell from the individual. The somatic cell is fused with an egg that has had its nucleus removed. The resulting cell is genetically identical to the individual because it contains the DNA from the individual’s somatic cell. The new cell behaves like a fertilized egg and develops into a blastocyst. ES cells can be harvested from the blastocyst and grown in culture. These ES cells could be used to treat the individual without encountering resistance from his or her immune system. Notice that I did not refer to this type of blastocyst as an embryo. This is because, technically speaking, an embryo is the result of the union of an egg and a sperm, which has not happened in this case.  Reproduced by permission of the NIH

Reproductive Cloning vs. Therapeutic Cloning 11/9/2018 Reproductive Cloning vs. Therapeutic Cloning Purpose of therapeutic cloning is to harvest Embryonic Stem cells for treatment  blastocyst destroyed Purpose of reproductive cloning is to make new person  blastocyst implanted in uterus  Cloning is something we hear a lot about these days. There are in fact two types of cloning: reproductive cloning and therapeutic cloning. Most people have heard of reproductive cloning. Dolly the Sheep, which was cloned in 1997, is the most famous example of reproductive cloning. Other species have also been cloned, but not (so far) a human. ES cell research does not involve reproductive cloning, although it can involve therapeutic cloning. It is important to understand the difference between the two.  This diagram shows how reproductive cloning is different from therapeutic cloning. Both types of cloning begin with SCNT. They differ in terms of what happens to the blastocyst.  The purpose of therapeutic cloning is to create ES cells for medical treatment. The blastocyst is destroyed when ES cells are harvested.  The purpose of reproductive cloning is the make a new organism. Rather than being destroyed, the blastocyst is implanted in a uterus, where it develops into a fetus.  Reproduced by permission of the NIH

What about Adult (Somatic) Stem Cells? 11/9/2018 What about Adult (Somatic) Stem Cells? Some Stem Cells live in the body of humans. Most of these cells are Multipotent. Multipotent Stem Cells can only be induced to become fewer tissues than Pluripotent Stem cells that are derived from Embryos. New research is showing that we can induce adult stem cells to become more pluripotent.

Sources and Targets 11/9/2018

Pluripotent Blood Stem Cells 11/9/2018 Pluripotent Blood Stem Cells

Potential Benefits Organ shortage (long term) 11/9/2018 Potential Benefits Organ shortage (long term) Tissues for Treatments (shorter term) Valves, Skin, Nerves for Spinal Cord Injuries Diabetes (Type 1)

Stem Cell Uses 11/9/2018

Patient Specific Stem Cell Therapy 11/9/2018

Promise of Stem Cell Research 11/9/2018 Promise of Stem Cell Research

Challenges 11/9/2018

11/9/2018 Major Ethical Issues For those who believe that the embryo has the moral status of a person from the moment of conception, research (or any other activity) that would destroy the embryo is considered wrong and should not take place. For those who believe otherwise, arriving at an ethically acceptable policy in this arena involves a complex balancing of a number of important ethical concerns. Although many of the issues remain contested on moral grounds, they co-exist within a broad area of consensus upon which public policy can, at least in part, be constructed. ETHICAL ISSUES IN HUMAN STEM CELL RESEARCH VOLUME I Report and Recommendations of the National Bioethics Advisory Commission Sept 1999

11/9/2018 Bibliography ETHICAL ISSUES IN HUMAN STEM CELL RESEARCH VOLUME I Report and Recommendations of the National Bioethics Advisory Commission National Bioethics Advisory Commission Sept 1999 Berg, Paul Biochem 118 Lecture Stanford University http://cmgm.stanford.edu/biochem118/Stem%20Cell.html Accessed 1/17/2005 Human Stem Cell Research Promise and Problems http://www.northwestern.edu/science-outreach/stemcell/stemcells.html Accessed 1/17/2005 Picture at the top http://science.howstuffworks.com/brain1.htm National Institutue of Health http://stemcells.nih.gov/info/basics/basics4.asp http://easyweb.easynet.co.uk/~sfl/rlb_stem.htm drawn image http://www.tracy.k12.ca.us/thsadvbio/ppt/Promise%20and%20Peril%20of%20Stem%20Cells.ppt