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CGM Stem Cells
Terms in this set (53)
3 types of stem cells
cancer stem cells
found in morula formed from fusion of egg and sperm
able to create an entire organism
can differentiate into any cell including:
embryonic and extraembryonic cellls and placenta
comes from totipotent cells of any of the three germ layers; inner cell mass of blastocyst
can differentiate into nearly all cells
can differentiate into a small number of different cell types
embryonic stem cells
inner cell mass of blastocyst
can differentiate into all embryonic tissues
adult stem cells
found in adult tissues
replenishes specialized cells and maintains turnover of regenerative organs (blood, skin and GI)
two types of adult stem cells derived from the bone marrow
hematopoietic stem cells
stromal stem cells
hematopoietic stem cells
can form all of the blood cell lineages
stromal stem cells
can form bone, cartilage, fat and CT
neural derived stem cells
can differentiate into brain tissue, hematopoietic cells and skeletal muscle
What is the difference between a stem cell and a progenitor cell?
both are unspecialized
but a stem cell can replicate and renew itself (progenitor cells cannot)
progenitor cells are more differentiated than stem cells
What adult tissues contain adult stem cells?
peripheral blood and blood vessels
What two cells act as a repair system for the body in adult organisms?
stem cells and progenitor cells
Which factor is used to inhibit differentiation of embryonic stem cells in mice?
Leukemia inhibitory factor (LIF)
Why do stem cells tend to be resistant to chemotherapy and radiation?
because they divide slowly and these processes are most effective against rapidly dividing cells
How can a cancer stem cell arise?
mutations in stem cells or early stem cell progenitors
from differentiated cells
host microenvironment factors
What does the division of a stem cell produce?
one copy of itself (self replication)
a specialized cell
What does the division of a progenitor cell produce?
two specialized cells (that can be different from one another ie: liver and kidney)
What is symmetric cell division?
undergone by stem cell
expands the number of stem cells
produces copies of the stem cell itself
What is asymmetric cell division?
undergone by stem cell
gives rise to a new specialized progeny and one copy of the replicating stem cell
What is terminal differentiation?
when a specialized cell is created
What are the two theories for stem cell renewal?
symmetric/asymmetric division and
stem cell niche
What comprises a niche?
constraints of the space
cellular components: stromal supporting cells, descendent/progenitor cells
acellular components: soluble and membrane bound molecules
paracrine and endocrine signals
What is a niche?
restricted and specialized tissue microenvironment that integrates local and systemic signals for the regulation and maintenance of resident stem cells
What is needed to culture human stem cells in vitro?
embryonic stem cells from the inner cell mass of a blastocyst
B fibroblast growth factor (inhibits differentiation)
mouse fibroblast feeder cells (which provide growth and attachment factors)
Fluorescence activated cell sorting (FACS)
process used to isolate stem cells
- suspension of fluorescently tagged cells sent under pressure thru narrow nozzle
fluorescent cells: negatively charged and can be separated
Markers commonly used to identify stem cells
Stage-specific embryonic antigen 3 (Embryonic stem cell and embryonal carcinoma)
CD4 and CD8 (WBC)
Stro-1 antigen (stromal, precursor cells and hematopoietic cells)
How can you stimulate differentiation in adult and embryonic stem cells?
-change chemical composition of the culture medium
-alter the surface of the culture dish
-modify cells by inserting specific genes
What is regenerative medicine?
the use of stem cells to repair or replace damaged tissues
uses stem cells and scaffolds
*often used synonymously with tissue engineering; but regenerative medicine places more emphasis on use of stem cells
What is a scaffold?
biodegradable, functions like a skeleton for the organ
replaces extracellular matrix that gives body tissues their structure; consists of tissues such as cartilage and muscle
What is tissue engineering?
use of cells, engineering and chemical methods to improve or replace the body's natural functions
Applications of tissue engineering
burn victim skin grafts
constructing new organs
Hematopoetic stem cells
best understood, routinely used
home to bone marrow after being transplanted
circulating blood levels can be elevated by administering gf
express CD34 and Thy-1 surface Ags
Sources of hematopoetic stem cells
adults: bone marrow, placenta and mobilized peripheral blood
Which growth factors can be administered to increase the levels of circulating hematopoetic stem cells?
granulocyte-macrophage colony stimulating factor (GM-CSF)
granulocyte colony stimulating factor (G-CSF)
What are the uses of bone marrow transplant?
immune system cancers
marrow doesn't produce cells
genetic diseases affecting bone marrow
autoimmune diseases attacking bone marrow
transplant between two genetically different individuals
cells removed from donor (same person receiving transplant) cancer cells and stem cells are separated, stem cells are re-infused
Graft-versus host disease
mature immunocompetent cells in transplant attack tissues of their new host
reduced by purifying and transfusing ONLY stem cells, that way they mature in the host and don't attack
acute- first 3 months
chronic- starts after 3 months, last lifetime
Sources of bone marrow stem cells
bone marrow harvest- directly out of bone
apheresis- filter peripheral blood cells and collect stem cells
umbilical cord blood- filter stem cells out
Somatic nuclear transfer
removal of cell from pt requiring tx
nucleus is removed from the cell
nucleus is injected into empty egg cell
division is encouraged
result: embryonic stem cells (therapeutic cloning) that can be differentiated into tissues/organs
organism (reproductive cloning)
Difference between therapeutic cloning and reproductive cloning
both use somatic cell nuclear transfer process
therapeutic: goal is to make embryonic stem cells
reproductive: goal is to make genetically identical organism
embryonic stem cells generated in somatic nuclear transfer are used to create different tissues for pt
no issues of rejection bc the stem cells come from the pt
Stem cell diseases
paroxysmal nocturnal hemoglobinuria
Genetic manipulation of stem cells
used in experiments as possible tx for inherited diseases
remove pt's stem cells-> insert functional gene copy-> transfuse
experiment for severe combine immunodeficiency had extreme adverse results
Clonal evolution model of tumor cells
cancer is formed through accumulation of genetic changes in cells and gradual selection of clones
cells proliferate with concomittant silencing of growth inhibitor genes and blunting of cell death
cancer is a proliferative disease
Cancer stem cell theory
Cancer stem cells have properties similar to stem cells and these undifferentiated CSC form a small fraction of tumor mass which is spared throughout tx and is therefore able to metastasize and cause relapse
cancer is stem cell disorder (not a simple proliferative disease)
assumed characteristics of cancer stem cells
1. ability to self renew
2. heterogenecity aka multidirectional differentiation
3. resistance to apoptosis
Importance of self-renewal of stem cells
1. can undergo infinite cellular divisions with only a few cells dividing at a time
2. long doubling time of stem cells (have time to repair DNA damage)
3. chromosomal preservation in the mother cells minimizes mutation in that cell
What two important genes do cancer stem cells most likely express?
Why is osteosarcoma evidence in support of the CSC theory?
osteosarcoma occurs close to growth plates in long bones where many stem cells reside and grow and develop
Why is colorectal cancer evidence in support of CSC theory?
colorectal cancer arises from the long-lived stem cells because the intestinal epithelial cells do not live long enough to accumulate tumor-inducing genetic changes
What is the order of cells beginning at the base of the colon crypt?
stem cells->proliferating cells->differentiating cells->apoptotic cells
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