Stem Cells Flashcards
What are the 4 characteristics of stem cells
- Not terminally differentiated
- Can divide w/o limit
- Undergo slow division
- when divide gives rise to 1 cell with stem cell characteristics, the other cell must be w/ the ability to be differentiated
What is a totipotent cell
A cell w/ the ability to give rise to embryotic and extraembryonic. Ex. a zygote
What do extraembryonic tissues support
These are cells that support embryonic development
What is a pluripotent cell
A cell w/ the ability to give rise to all cells of the embryo and then adult tissues
What is multipotency
A multipotent cell has the ability to give rise to different cell types of a given lineage (adult stem cells)
How is the amount of somatic cells per location dictated
Each tissue has a fixed number of founder cells depending on the proportion of the body part. These founder cells are programmed to have a fixed number of divisions and are controlled by short-range signals that operate for a few hundred cell diameters.
What is a strategy for growth control
Transit amplifying cells
What are transit-amplifying cells
They are cells that divide frequently and are a strategy for growth control because they only have a finite number of divisions.
what are 2 ways we maintain a steady pool of stem cells
- Divisional Asymmetry
2. Environmental Asymmetry
What is the difference between environmental and divisional asymmetry
In divisional, you are guaranteed a stem cell. In environmental, the environment may influence one of the 2 stem cells to make it into a differentiated cell
How do stem cells differentiate
In stages of differentiation, there are multiple factors that combine to produce EPIGENETIC markers in the cells DNA that restrict DNA expression, so they can only differentiate into certain cells.
what is the immortal strand hypothesis
Instead of randomly segregating their DNA in mitosis, the adult stem cell will segregate asymmetrically to give the terminally differentiating cell (non-stem cell) the strand that’s more likely to mutate.
“By retaining the same set of template DNA strands, adult stem cells would pass mutations arising from errors in DNA replication on to non-stem cell daughters that soon terminally differentiate (end mitotic divisions and become a functional cell). Passing on these replication errors would allow adult stem cells to reduce their rate of accumulation of mutations that could lead to serious genetic disorders such as cancer.”
What is the stem cell hierarchy
Totipotent embryonic stem cell
Pluripotent embryonic stem cell
Multipotent stem cell
Pros/Cons of embryonic stem cells
Pros: Develop into different cell types, indefinite proliferation in culture, can integrate well with an embryo if put back into a blastocyst
Cons: Unrestricted development potential, can cause tumors, on their own ES are not capable of generating a body plan (can lead to teratomas)
How can we dictate was an embryonic stem cell will differentiate into
Cultured embryonic stem cells can be placed into a culture with various growth factors (retinoic acid, macrophage colony-stimulating factor, dibutyryl cAMP, fibroblast growth factor) to make various tissues (adipocytes, neurons, macrophages, smooth muscle, astrocytes, etc.)
How can pluripotent stem cells impact pt tx?
From a blastocyst, an inner cell mass is removed and pluripotent stem cells can differentiate into skin, nerve, pancreatic cells and be transplanted to a pt.
(severe immune deficiency, DM, Parkinson’s, spinal injury, demyelination, MI)
which transcription factors maintain pluripotent stem cells
Nanog
Oct4
Sox2
Fox D3
“Nanna only sees fox”
what is required for early stages of pluripotent cell differentiation
GCNF (germ cell nuclear factor)
What are 2 growth factors found in pluripotent cells
- Cripto
2. GDF-3 (growth differentiation factor)
Where are adult stem cells found and how do they restrict gene expression
Adult stem cells are found in issues. They are controlled by molecular restraints on gene expression and these are heritable during many rounds of cell division. *Sometimes they show relaxation of these restrictions in altered environments
2 kinds of adult stem cells
- Bone marrow-derived mesenchymal stem cells (BMSCs): transplant
- Adipose-derived mesenchymal stem cells (AMSCs)
Some uses of cord blood?
Many diseases can be treated with cord blood stem cells, like leukemia, myelomas, thalassemia, sickle, etc. Cord blood stem cells are undifferentiated and do not have any gene manipulation.
Challenges of regenerative medicine
Harvested cells retain properties of its original tissue type, cannot be coerced to express the characteristics of a radically different tissue type, delivery, and proper integration, reaching the numbers of cells in pure form, embryonic or fetal-derived grafts may be immunogenic, some transplantation sites may be immunologically privileged.
Where do both hematopoietic and stromal stem cells come from?
Bone marrow
What do hematopoietic stem cells (HSCs) differentiate into
blood components. Note: HSCs are found in bone marrow, cord blood, and peripheral blood.
What do stromal cells (aka mesenchymal stem cells MSCs) differentiate into
Connective tissues, tissues. Note: MSCs are found in bone marrow, whartons jelly, adipose, and tooth pulp
what are the 2 kinds of pluripotent cells used in regenerative medicine?
Patient derived (iPS) Non-patient derived (ES)
What are the key determinant of ES (non-patient derived pluripotent cells) cell character
- Oct3/4
- Sox2
- Myc
- KIf4
These are gene regulatory proteins
what are alternative sources for human ES cells
iPS (induced pluripotent stem cells)
somatic cell nuclear transfer (SCNT)
How does SCNT bypass immune rejection?
SCNT produces cells that are custom made for a pt. This solves tissue rejection as the cells express pt genes.
Ethical implications of SCNT
Requires formation and destruction of human embryos to obtain the pluripotent embryonic stem cells
What is the pathway for SCNT?
- Obtain eg cell and somatic cell
- Remove the nucleus from the eff cell
- Fuse the egg cell and somatic cell together
- Stimulate cell division
- Form a blastocyst (contains a pluripotent inner cell mass)
- Extract the inner cell mass
- Culture the pluripotent embryonic stem cells
where do we inhibit cloning in the SCNT pathway
- If we inhibit cloning at the fusion point, there is no therapeutic application…so not here
- Prohibiting implantation of the inner cell mass restricts reproductive cloning but allows therapy to continue
Challenges to SCNT
- Inefficient (may need hundreds of oocytes…where would we get them?)
- Technically demanding…needs to be at many hospitals
