Stem Cell Applications Flashcards
What is a stem cell?
A primitive cell that can clone itself or create daughter cells that are more specialized
Stem cell characteristics
1) Not terminally differentiated
2) No limit to division
3) Division leads to 1 stem cell daughter and another daughter that can be differentiated
Main characteristic of Adult stem cells
-They are tissue specific (epidermal stem cells = epidermal cell types)
What are the three levels of potency?
1) Totipotency - can make all cells (zygote)
2) Pluripotency - give rise to all embryo cells and subsequent adult tissue cells (blastocyst)
3) Multipotency - give rise to cell type of a certain lineage; partially committed (adult stem cells) (Various tissues)
How many cells is a zygote totipotent for?
16
What does cell differentiation depend on?
What you feed into the culture
What are founder stem cells?
- Stem cells that have fixed number of division (think finger: you only have 5)
- Each tissue has fixed number of FC populations
- Controlled by short-range signals
What are Transit Amplifying Cells?
-Committed cells
Key: they divide a finite number of times before becoming differentiated
-THEY DIVIDE FREQUENTLY
-move from stem cell -> committed tissue cell
What is the key to stem cell maintenance and how is it accomplished?
-50% of daughter cells must remain as stem cells and retain original DNA
1) Divisional asymmetry - one specialized daughter, one stem cell characteristic daughter
2) Environmental asymmetry - two identical cells made but environment alters
What is the Immortal Strand Hypothesis?
- Some tissues’ stem cells retain original DNA to PREVENT GENETIC ERRORS
- Divisional asymmetry preserves
What are the types of stem cells?
1) embryonic
2) adult/tissue specific
3) fetal
4) cord blood
5) Induced pluripotent
6) somatic cell nuclear transfer
Stem Cell Hierarchy
-Two types: Embryonic and Adult
SC differentiate into specialized cells in stages -> stages need multiple factors (epigenetic) to restrict DNA expression in order to produce proper cell -> DNA expression can pass onto daughter cell or daughter remains stem cell
Embryonic Stem Cells
- From blastocyst
- Proliferate indefinitely, unrestricted potential (totipotent and pluripotent)
- CAN BECOME A TUMOR if injected late into embryo development
- Various tissues form when injected into host animals
What are Tertomas?
- A tumor with a variety of different tissues
- Made from Embryonic stem cells —> can’t generate a full body plan on their own like a full embryo
What are the transcription factors in pluripotent cells and why are they important?
TFs:
1) Nanog 2) Oct4 3) Sox2 4) FoxD3
-Necessary for establishment and maintenance of pluripotent sc
Adult Stem Cells
- Fixed in tissues with degree of plasticity
- respond to growth and repair demands
- Restricted capacity and growth potential
Hematopoietic & Stroma/Mesenchymal Stem Cells
- From bone marrow
- HSC = blood related
- MSC = fat, heart, muscle, etc.
Cord Blood Stem Cells
- Undifferentiated, adult stem cells
- Can treat over 70 disease
What are the central strategies of Regenerative Medicine?
1) Pluripotent cells
2) Differentiated in vitro
3) Reprogram primary cells
Challenges for Regenerative Medicine?
1) Producing right amount of proper cells
2) Proper integration into tissues
3) Embryonic/fetal grafts might be immunogenic
What are two adult stem cell therapies?
Neuro-regeneration is big
1) Bone marrow derived mesenchymal stem cells
2) Adipose derived mesenchymal stem cells
i.e. bone and fat
What does somatic cell nuclear transfer (SCNT) allow us to do?
- Bypass host rejection by taking nucleus from a somatic cell and inject it into donor oocyte in place of oocyte nucleus
- Allows or removing controversial embryo step
What gene regulatory proteins determine embryonic stem cell character?
Oct3/4, Sox2, Myc and KIf4
-Useful to know if you want to maybe turn adult stem cells into embryonic stem cells
What are Induced Pluripotent Stem Cells?
- Undifferentiated Adult stem cells (from patient) that are turned into pluripotent stem cells via DNA recombination
- Can’t become any specialized cell but a good amount
- High potential for teratomas
What are the steps for Somatic Cell Nuclear Transfer?
1) Fuse egg (no nucleus) with a somatic cell (with nucleus)
2) Stimulate cell division
3) Allow blastocyst to form
4) Extract inner cell mass from the blastocyst (not implanting blastocyst at this stage restricts cloning – think DOLLY!)
5) Culture the new pluripotent embryonic cells
DOLLY made this way!!
Challenges of SCNT in Disease Treatment
1) Inefficient - may need hundreds of oocytes
2) Demanding — skilled staff needed
Type I Diabetes??? Make Beta cells???
