Stem cells Flashcards
Embryonic stem cells
- From blastocyst
- Can proliferate indefinitely
- Unrestricted developmental potential
- Can become any cell of organism (even into germ cells)
- If injected into an embryo at a later stage or into an adult, they don’t get the right sequence of cues that is needed for differentiation
- Often become tumors when injected in
Can embryonic stem cells be put back into the embryo?
Yes
Teratomas
Come from embryonic stem cells
Tumors can have teeth, other body parts (b/c ES cells aren’t able to generate body plan)
Transformation
Normal cell starts to divide inappropriately—into cancer
Embryonic stem cells come from where?
Inner cell mass of blastocyst
Can’t be put back into unfertilized egg to become organism
ES cells
Can be derived from human embryos
Can be coaxed to differentiate into different cell types
Can be injected into adult organs to replace damaged parts
Been used successfully in brain
*we don’t want to inject a completely undifferentiated ES cell
Different Cell Types from ES cells
We try and culture them outside the blastocyst, get into lineage that is safer and inject directly to site of damage
How to get cultured embryonic stem cells to become neurons?
Use retinoic acid (steroid hormone)
Can trick cells into turning on certain TF’s
Cell types in nervous tissue are usually derived using what?
Use fibroblast growth factor
Easiest way to induce embryonic stem cells to turn into different tissues?
Chemicals
How are ES cells derived?
Grow on culture or leave it alone and becomes organism
Human ES cell growth
Fibroblasts help create happy medium for cells
Plate blastocysts and then bring in the blastocyst cells
Isolation of Embryonic Stem cells
When we differentiate the cells in culture they will be heterogeneous and we want to identify homogenous populations
Nerve and muscle cells are found in a complex mixture when growing them. Why?
Because retinoic acid stimulates both
Application of ES cells
Can solve rejection problems
Founder cells are ______
Multipotent
Derived to make a certain type of tissue (heart founder cell, liver founder cell etc)
They divide, giving rise to daughter cell which will remain a stem cell and to a transient amplifying cell
Liver damage→founder cell will be used
Mature stem cell
Pro: Probably came from your own cells
Con: Get to level of senescene pretty quickly
Early stem cell
Immortal, continue to grow
Potential for rejection
Somatic cell nuclear transfer
Nucleus taken from somatic cell of patient and injected into oocyte of a donor replacing the oocyte nucleus
First step in closing
Solve immune rejection b/c you’d use your own genome
Challenges for Regenerative Medicine and Transplantation Therapy
- Production of required cell type in sufficient numbers and pure form
- What cell to transplant
- Delivery and proper integration
- tissue/immune rejection
- Embryonic- or fetal-derived grafts may be immunogenic
- Some transplantation sites may be immunologically privileged
Adult stem cell problems
Immune rejection
Outside manipulation of adult stem cells can reprogram them
True
Strategies of regenerative medicine
Induced
Reprogramming
Somatic cell transfer
Adult stem cells that we can take out of body and manipulate and put back in
Bone marrow
Skeletal muscle
Heart muscle
Skin
Bone marrow stem call can become
Every blood cell that we need
Can also become other tissue
Adipose derived stem cells
People have successfully made them into different kinds of cells
Basal layer of many tissues (gut, epithelial) is where you have dividing stem cells, adult derived
True
Basal stem cells
Basal layer
Has stem cells. They divide to maintain the basal layer and also supply cells that move to other layers, undergo change in gene expression and differentiate
Stem cells provide an indefinite supply of fresh differentiated cells
True
Cells that cross the basal lamina can become what?
Metastatic tumors
Olfactory Neurons
Lining of nose is epithelium
Adult stem cells give rise to these cells
Olfactory receptors
- Free surfaces of cilia have odorant receptor proteins
- A type of G-protein coupled receptor
- Each neuron expresses only one of these genes
What you smell is biscuits and gravy
That has one receiving signal and one axon
Example of Adult Stem Cell Therapy
Bone marrow transplants
Fibroblasts (skin sample)
Induced pluripotent stem cells-they go back to embryonic stem cell state so that they can become every tissue
Our bone marrow contains many different stem cells
True
Mesenchymal cells (can get to brain and fix brain damage)-they can become neuronal-like cells
Some adult stem cells can become multiple lineages (from adipose too)
Somatic Cell Nuclear Transfer
(SCNT)
How to avoid ethical dilemma
We take unfertilized egg and remove nuclei from somatic cell (skin cell for example), it’s your genome, put it into egg and start developmental process, then use blastocyst cells to put into dish, turns into pancreatic beta cells into pancreas and you won’t have rejection problems
Reprograming without having to go through embryo step
Other uses for SCNT
We can analyze potential toxins to our body by using cells that are made from our body
We can take a diploid genome, put it into an egg and get life. Big finding b/c it opened up its genes that were in heterochromatin and now it’s an embryonic stem cell
Induced pluripotent stem cells (iPS)
Inject pluripotent genes into adult stem cells
Somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells by defined, limited sets of transcription factors
Taking cell that has gone through many divisions and trying to get it back to the embryo
Problems with all these dividing cells
Genetic drift and cell growth
3 different protocols used for ES cell differentiation
As embryoid bodies
Differentiated on stromal cells
On extracellular matrix proteins
Regeneration of olfactory receptor cells is one of the only
few instances of adult neurogenesis in the CNS.
True
Adipose and bone marrow have shown the ability to differentiate in vitro and in vivo into to chondroycytes,
myoblasts, osteoblasts, pancreatic betacells and neuronal-like cells
True
Adult stem cells (bone marrow) can regenerate neuronal cells in the brain
True
Reprograming
Inject proteins from pluripotent cell into adult stem cell
Somatic cell + Embryonic stem cell=
Cellular fusion–> pluripotent hybrid cell–> blood cells or neural cells
Stem cell- key phrase
Self-renew
Undifferentiated, differentiated etc
Stem cells (pluripotent)
Adult stem cells (multipotent)
Quiescent stem cells
Stem cells (pluripotent): undifferentiated
Adult stem cells (multipotent): slightly differentiated
Quiescent stem cells: fully differentiated
Immortal strand hypothesis
ALL of original daughter strand chromosomes go into the daughter cell, they all line up on one side during mitosis (thanks to signaling at kinetochores)
Embryonic stem cells: types
found in embryo
Totipotent (from zygote–>whole organism)
Pluripotent: inner cell mass, blood cells, cardiac muscles, neural cells etc, can be grown indefinitely, main one used in research
Adult stem cells
found in many organs
Multipotent
Specializing potential is limited to one or more cell lines
e.g. Mesenchymal stem cell –> Bone or cartilage or connective tissue etc
Tough to grow
iPS cells
Take normal cell (e.g. skin cell), give it genetic instructions in dish, they can reverse and be able to be any cell and become pluripotent
Skin cell–>iPS cell–> Blood cell
Good for tissue regeneration, genetic matches for tissues,
