Stem Cells Science in the News Adapted by your teacher Ms. Boehm

• What is a stem cell? • Where do stem cells come from? • What are stem cells good for?

Stem Cell Capable of dividing and making new cells of many types 2. Capable of self-renewal (One daughter cell is like parent) Differentiation: the process by which a cell undergoes a change to become a specialized cell type

Pluripotent cell (Embryonic Stem Cell) Differentiation occurs step-by-step Stem Cells Pluripotent cell (Embryonic Stem Cell)

Differentiation occurs step-by-step Stem Cells Pluripotent cell (Embryonic Stem Cell) Multipotent cell (Adult Stem Cell)

Embryonic Stem Cells Bridge the Gap from the Fertilized Egg to the Fully Formed Organism Adult Mouse (Cell Division and Differentiation) Fertilized Egg (“Totipotent”) Embryo (“Pluripotent” Cells)

Each of these different Muscle cell Lens cell IMPORTANT!!!!! Each of these different cell types has the same DNA Pancreas cell

How do cells with the same DNA end up so different? Protein A Muscle Cell Gene A is on Gene B is off DNA X Gene A Gene B Lens Cell Gene A is off Gene B is on X Pancreas Cell Gene A is on Gene B is on

Where do stem cells come from?

Embryonic Stem Cells Pluripotent Derived from the blastocyst 3-5 days after fertilization Egg + Zygote Blastocyst Fetus Sperm

Embryonic Stem Cells A blastocyst contains 200-250 cells. inner cell mass (embryo) trophoblast (placenta) A blastocyst contains 200-250 cells. The inner cell mass is only 30-34 cells There are 10,000,000,000,000 cells in a human adult

1. Obtain cells from blastocyst Inner cell mass

2. Grow cells on a dish in the lab

ESCs grow on “feeder” cells Provides nutrients to stem cells Structural support for growth

3. Cells grow in the dish Able to self-renew Actual stem cells seen under microscope

ESCs have the potential to produce different types of cells Liver Muscle Blood Skin

And Where are the adult stem cells? Neural Brain cell types Skin Skin and hair Gut Gut derivatives eye Eye cell types Blood & marrow Blood cell types Each type of adult stem cell is found in the tissue it makes. A single totipotent stem cell can grow into an entire organism. Pluripotent stem cells cannot grow into a whole organism, but they can become any other type of cell in the body. Multipotent stem cells can only become particular types of cells: e.g. blood cells, or bone cells. • mixed among the differentiated cells in that tissue

Different Types of Stem Cells: What and Where? Embryonic Adult Potential: • Can make all cell types (TOTIPOTENT) • Only make certain cell types (MULTIPOTENT) How they are obtained: • Isolate from inner cell mass of embryo (blastocyst stage) • Found in from adult tissue (but for most types we don’t know how to find them)

What are stem cells good for?

replace dead or damaged cells Stem cells could replace dead or damaged cells Stem cells could be transplanted directly into diseased tissue where they would become the desired cell type or Stem cells could be coaxed into specializing in the lab and then transplanted as differentiated tissue Replacement is permanent! (stem cells are self-maintaining)

A bone marrow transplant is an adult stem cell transplant Leukemia

A bone marrow transplant is an adult stem cell transplant Implant with Blood Stem Cells Blood Cells Regenerated Leukemia (remove bone marrow) 1. Stem cells contribute to all blood cell types 2. After several months, the new cells still populate blood

Challenges of using adult stem cells

Challenge 1: Not yet found in all tissues Pancreas

Challenge 2: Not easily accessible in all tissues Brain How are we going to get stem cells from the brain of the patient?? Muscles

Challenge 3. Rare & Difficult to isolate Need “markers” to differentiate stem cells from other types of cells

Embryonic vs. Adult Stem Cells Embryonic Stem Cells Technical difficulties: How to direct specific differentiation Controversy: Ethical considerations Adult Stem Cells Technical difficulties: Need to improve isolation techniques and optimize culturing conditions

Embryonic stem (ES) cells may be used to treat deteriorating brain cells Parkinson’s Disease: Selective death of subset of neurons Partial replacement of lost neurons Mouse model of Parkinson’s disease Inject mouse ES cells Into diseased brain Could be used to treat Alzheimer’s, Huntington’s, spinal cord injury, etc… Still in experimental infancy, but shows much promise for many diseases.

Where do the blastocysts come from? In vitro fertilization Aim to help infertile couples conceive children Egg is fertilized with sperm in the lab LAB Zygote Blastocyst Sperm Egg Fertilization

In vitro fertilization Implanted back into woman Blastocyst Frozen Embryonic stem cells

Problem of immune rejection Each person has own unique set of DNA Body’s immune system rejects cells that do not belong to the individual Need to match donor cells/tissues/organs to recipient Stem cells used must be genetically compatible with patient Embryonic stem cell lines derived from IVF will not be compatible Somatic Cell Nuclear Transfer (SCNT) = THERAPEUTIC CLONING

Somatic cell nuclear transfer (SCNT) Somatic Cell = Any cell of the body, except sperm and egg Nuclear Transfer = Moving the genetic material (DNA) of one cell to another Nucleus of an egg is removed and replaced with the DNA of an adult cell Creates patient-specific ES cell line

Therapeutic cloning vs. Reproductive cloning

What is cloning? Clones = INDIVIDUALS that are genetically identical to another  Identical twins are clones Clones = CELLS that are genetically identical to another =

CLONING CLONING

REPRODUCTIVE CLONING THERAPEUTIC CLONING Need to be implanted into a surrogate mother “Personalized” Stem cells for tissue therapy

1. Remove nuclear DNA from egg

1. Remove nuclear DNA from egg

2. Insert DNA from donor into egg

2. Insert DNA from donor into egg

THERAPEUTIC CLONING “Personalized” Stem cells for tissue therapy

Advanced Cell Technology, Worchester, Massachusetts