Define the term stem cell:
An undifferentiated cell that can self-renew and has the ability to differentiate into tissues, organs and specific cell types
What are the two main types of stem cells?
- Embryonic stem cells
2. Adult stem cells
What are the 3 broad uses of embryonic stem cells?
- Regenerative medicine
- Modelling and treating human diseases
- Understanding and treating birth defects
What is an embryonic stem cell?
- Embryonic stem cells are pluripotent stem cells derived from the inner cell mass of the embryo that was wide differentiation potential
- Self-renewing
- Can be differentiated into different tissues by exposing them to different inductive signals/factors
What are the 4 characteristics of embryonic stem cell?
- ES cells can self renew
- ES cells express pluripotency markers such as Oct4
- ES cells have long telomeres at the end of chromosomes
- ES cells can be propagated in vitro in the presence of growth factors e.g. FGF-Bs and Wnts
What is a totipotent stem cell?
- A totipotent stem cell is an undifferentiated cell capable of differentiating into every cell of an organism including all embryonic tissue such as the placenta e.g. zygote
What is a pluripotent stem cell?
- A pluripotent stem cell is an undifferentiated cell capable of differentiating into all 3 germ layers (ectoderm, mesoderm and endoderm) and their derivative tissues e.g. inner cell mass cells from blastocyst
What is a multipotent stem cell?
- Describes stem cells which have the potential to differentiate into different cell types within the same tissue type e.g. haemopoietic stem cells can differentiate into different blood cells
Describe an example of ES cell use to treat diabetes type I:
- An example of the regenerative medicine application: ES cells can be differentiated into beta-like cells by exposing them to specific factors and signals; those differentiating into beta-cells can be identified by the expression of markers e.g. insulin secretion in response to glucose. These cells can be transplanted into a diabetic mouse and ‘cure’ its diabetes.
Potential Problems with ES cells:
- Many current approaches often yield heterogeneous cell populations in vitro
- Transplanted ES derived cells many not behave normally in vivo
- ES derived cells may have tumorigenic potential (depending on environmental signals they receive e.g. if transplanted under the skin of an adult mouse)
- ES derived cells may be rejected immunologically
- Ethical concerns regarding the generation of human ES cells
What is an adult (somatic) stem cell?
- Adult (somatic stem cells) are multipotent stem cells derived from mature organs that naturally replenish old/diseased tissues in the body
- They are found in regulated microenvironments
Give examples of adult (somatic) stem cells in the body:
- Skin stem cells
- Haematopoietic stem cells
- Mesenchymal stem cells
What are the advantages and disadvantages of ES cells:
Advantages:
- pluripotent: can differentiate into ANY cell type of the body
- large numbers can be harvested from embryos
Disadvantages:
- potential for undesired tumour formation
- may cause immune rejection
- high ethical controversy
What are the advantages and disadvantages of adult (somatic) stem cells?
Advantages:
- Less likely to cause immune rejection as the patients own cells can be used
- Less likely to form tumours
- Less ethical concerns
Disadvantages:
- Multipotent: cannot differentiate into every cell type like ES cells; limited outcomes
- Limited numbers available and more difficult to isolate
What is cloning?
Generating genetically identical copies of DNA, cells or organisms
In the context of tissues and organisms what are the two main types of cloning?
- Reproductive cloning: - cloning an entire organism via SCNT
- Therapeutic cloning:
- can be used to generate stem cells from an individual to treat and model diseases
Describe the SCNT method within cloning:
- SCNT (somatic cell nuclear transfer) method: involves enuncleating a donor egg and replacing the nucleus with the the nucleus from a somatic cell from the organism that you are trying to clone/clone tissues from. This embryo can be implanted into a surrogate (reproductive cloning) or grown in culture (therapeutic cloning)
What is an induced pluripotent stem cell?
- An iPS cell is a cell derived from adult tissue that is reprogrammed back to a pluripotent stem cell with certain factors
How are pluripotent stem cells made?
- Cells isolated from patient (skin or fibroblast cells) and grown in dish)
- Cells are treated with reprogramming factors- Oct4, Sox2, c-Myc and Klf4
- Wait a few weeks
- Pluripotent stem cells are generated
- These iPS cells can be exposed to different conditions to cause them to differentiate into different cell types.
What are advantages of iPS cells over ES cells?
- iPS cells are patient specific so there will be no immune rejection
- iPS cells have less ethical considerations
What is the function of the 4 factors used in making iPS cells?
- Oct4 and 2. Sox2: activate Nanog to establish pluripotency and block differentiation
- c-Myc:
opens chromatin making genes accessible - Klf4:
prevents cell death
