Stem Cells The Biotech issue that may no longer be an issue. Use WiCell.org main page and Outreach for videos

What are stem cells?  “Blank slate” or unspecialized  Under right conditions, can become any cell type in our body.

Where do stem cells come from? Two general sources:  Embryonic Stem Cells (ESC)  Adult Stem Cells (ASC)  Embryonic Stem Cells (ESC)  Adult Stem Cells (ASC)

Human Development Zygote: fertilized egg Cells divide. 5 – 6 days later, blastocyst implants in uterine lining. Cell division video Cell division video – internet link Cell division video Cell division video – internet link Cell division video Cell division video – intranet link Cell division video Cell division video – intranet link

Blastocyst has two parts – trophoblast (will become placenta) and inner cell mass (ICM) which are embryonic stem cells (ESC) Blastocyst has two parts – trophoblast (will become placenta) and inner cell mass (ICM) which are embryonic stem cells (ESC) Ready to implant in uterine lining Ready to implant in uterine lining stemcells.nih.gov/info/ scireport/appendixA.asp Human Development

Totipotent: Able to become all types of cells. (Ex. zygote) Pluripotent: Able to become most types of cells. (Ex. Inner Cell Mass can become everything except placenta) Pluripotent: Able to become most types of cells. (Ex. Inner Cell Mass can become everything except placenta) Multipotent: Able to become some types of cells. (Ex. Bone marrow cells can become different types of white blood cells, but cannot become muscle or nerve cells)

Human Development Undifferentiated: Have not decided to become a type of cell yet. (Ex. Zygote) Differentiate: Decide to become a cell type. Happens after blastocyst stage. (Ex. When placed in a dish, ESC’s will spontaneously differentiate into... Video – internet; video - intranet)Videovideo Differentiate: Decide to become a cell type. Happens after blastocyst stage. (Ex. When placed in a dish, ESC’s will spontaneously differentiate into... Video – internet; video - intranet)Videovideo

Embryonic Stem Cells What signals did they receive to become these types? If we can figure out how to cause the entire dish of cells to become one type of cell...

Human Development A model for understanding human organ and tissue function and development Prevention of birth defects and cell- based diseases

Drug Screening Trials conducted on pure populations of cells in vitro, before administering them in vivo

Regenerative Medicine “Holy Grail” Human embryonic stem cells can provide a potentially unlimited source of cells for transplantation therapies

U.W. Researchers: Dan Kaufman, M.D., Ph.D. and Dong Chen, M.D., Ph.D. Bone marrow transplants offer a cure for many patients with leukemia, lymphoma, and multiple myeloma. Unfortunately, because of lack of appropriate donors, only about one- third of patients who require bone marrow from an unrelated, matched donor can actually obtain a transplant. Embryonic Stem Cells to Blood Cells

Parkinson’s disease is caused by the death of a specific type of neuron (dopaminergic neurons). 1.5 million people affected in the U.S. Fetal tissue transplants have been successful, but the source of tissue is inadequate. Differentiate Stem Cells to Neuronal Cells UW Researchers: Su-Chun Zhang, M.D., Ph.D & Clive Svendsen, Ph.D

Pancreatic  -Cell Differentiation of ES Cells Juvenile onset diabetes is caused by the death of specific pancreatic cells (islet  cells). 1 million people affected in the U.S. More than 15% of U.S.Health Care dollars are spent in taking care of these patients. The transplantation of pancreatic islet  cells has been successful, but the source of cells in inadequate. Juvenile Onset Diabetes UW Researcher: Jon Odorico, M.D.

Differentiate Stem Cells to Bone Cells BoneCartilage 1. Post Menopausal Osteoporosis, Age-related Osteoporosis 2. Sports Injuries 3. Joint Replacements/ Surgical repair 4. Developmental bone defects

Embryonic Stem Cells All of this work requires being able to grow ESC’s without differentiating unless you tell them to do so. Dr. James Thomson – discovered how to grow ESC’s without differentiation in 1998.

Where do ESC’s come from? IVF – in vitro fertilization In 2004, 29% of embryos were destroyed while 41% were donated to ESC research. Once ICM is removed, blastocyst is no longer viable. VideoVideo – internet; video - intranetvideo VideoVideo – internet; video - intranetvideo

ESC’s limitations Destruction of blastocyst - videovideoDestruction of blastocyst - videovideo

ESC’s limitations Destruction of blastocyst Tissue is not yours which can lead to immune system rejection Solution? Therapeutic Cloning Dedifferentiate: return to an undecided or undifferentated state.

Adult Stem Cells (ASC)

ASC’s All types are multipotent. Sources -Umbilical cord -Bone marrow -Adipose tissue (fat) -skin -Umbilical cord -Bone marrow -Adipose tissue (fat) -skin Stem Cell Summary Video Adult stem cells- 3:20 – 5:40 Stem Cell Summary Video Adult stem cells- 3:20 – 5:40

ASC’s Uses: -Leukemia (bone marrow) -Skin grafts Uses: -Leukemia (bone marrow) -Skin grafts

ASC’s Limitations: -Multipotent -Hard to find Limitations: -Multipotent -Hard to find

iPS Cells Induced pluripotent stem cells -2007, Dr. James Thomson -4 genes added to differentiated cells (e.g. skin cells) -Cells dedifferentiate and become stem cells -No blastocyst is produced Induced pluripotent stem cells -2007, Dr. James Thomson -4 genes added to differentiated cells (e.g. skin cells) -Cells dedifferentiate and become stem cells -No blastocyst is produced Sciencenow iPS Video Heart cells from skin cells Sciencenow iPS Video Heart cells from skin cells