Stem cells Flashcards
1
Q
cell origin
A
- Body is made up of ~ 220 different kinds of specialised cells such as muscle cells, nerve cells, fat cells and skin cells
- Different cells in the body come from stem cells
2
Q
importance of stem cells
A
- A stem cell is a cell that is not yet specialized
- Stem cells:
o Can self-renew to make more stem cells: sometimes after long periods of activity, mitotically divide, resulting cells continue to be unspecialized
o Can differentiate into a specialized cell type
o Have extraordinary replication potential
o Present throughout life
o Resident stem cells maintain tissue homeostasis in response to perturbations
3
Q
tissue differentiation
A
- With a few exceptions, all cells contain the same DNA/genome
- Under certain physiologic or experimental conditions stem cells can specialize = differentiation
- Internal signals: changes in transcription or expression of genes expression regulates cell differentiation
- External signals: chemicals secreted by other cells, physical contact with neighbouring cells, molecules in the microenvironment of the cell
4
Q
differentiation
A
- The higher the degree of differentiation, the lower the replication potential of the cells
Human hematopoietic cells:
- ~ 1011 new blood cells produced daily
- Organized in a hierarchy
- Hematopoietic stem cells in the bone marrow give rise to progressively more lineage-restricted, differentiated progenitors with reduced self-renewal capacity, which in turn produce functionally mature blood cells
- Final cell types are terminally differentiated and do not divide
5
Q
types of stem cells
A
Embryonic Stem Cells:
- Can differentiate into all cell types present in an organism
o Immortal
Adult Stem Cells = somatic stem cells:
- Embryonic stem cells become fetal stem cells and with the birth mature into adult stem cells
- Are the reserve supply of cells that can multiply when needed (repair/regeneration)
6
Q
blastocyst
A
- Blastocyst: consists of ~100 cells
o Inner cell mass ~30 cells: Becomes embryonic disc, which will form embryo and three or four extraembryonic membranes
o Trophoblast: Display immunosuppressive factors. Participate in placenta formation
o Blastocoel” Fluid filed cavity
- Blastocyst enters uterine cavity ~ 4-5 days after fertilization
7
Q
potency of stem cells
A
- Potency specifies the differentiation potential into other cell types
- Main difference between embryonic stem cells and Adult stem cells is the type of potency
- Totipotent
- Pluripotent
- Multipotent
- Unipotent
- Induced Pluripotent
8
Q
totipotent stem cells
A
- The only totipotent cells are the fertilized egg and the cells produced by the first few divisions
- Totipotency in strict sense is demonstrated by the ability of an isolated cell to produce a fertile, adult individual
- Ovum derived cytoplasmic (non-genetic) factors are critical components of totipotency
- Totipotent stem cells give rise to somatic stem/progenitor cells and primitive germ-line stem cells
9
Q
pluripotent stem cells
A
- Descendants of totipotent cells
- Characterized by self-renewal and a differentiation potential for all cell types and tissues of the adult organism = multi-lineage differentiation
- Not capable of undergoing development on their own to form an entire organism
- Embryonic stem cells are considered pluripotent
- Ability to differentiate into multiple cell types is called plasticity
10
Q
multipoint stem cells
A
- Potential to differentiate into multiple, but limited cell types (multi-lineage differentiation)
- Most adult stem cells like tissue stem cells and cord blood stem cells are considered multipotent
11
Q
unipotent stem cells
A
- Arise from multipotent cells
- Will only give rise to one cell type, but can also self-renew (haematopoetic-, muscle- stem cells, most epithelial cells)
12
Q
embryonic stem cells
A
- Arise from multipotent cells
- Will only give rise to one cell type, but can also self-renew (haematopoetic-, muscle- stem cells, most epithelial cells)
- Can be grown in vitro and propagated in their undifferentiated state while retaining a normal karyotype = embryonic stem cell line
- Maintain the property of multilineage commitment over time -> can differentiate in vitro into all cell types present in an organism
- Embryonic stem cell marker: Oct4
- Ethical and moral discussion on when life starts
- No human application yet
13
Q
IVF
A
- Process of fertilization by manually combining an egg and sperm in a laboratory dish (e.g. when infertility problems are present)
- The fertilised egg (zygote) is cultured for 2–6 days in a growth medium and then implanted into a woman
- Several zygotes cultured at the same time – excess frozen
o Saved for later implantation
o Donated for research purposes with informed consent, tight regulations - Ethics
14
Q
somatic stem cells - adult stem cells
A
- Important for growth and to maintain tissue homeostasis by replenishing senescent or damaged cells
- Maintenance and regeneration of tissues dramatically decreases with age
- Thought to reside in a specific area of each tissue, called a “stem cell niche”
- Can be extracted from many areas of the body including the bone marrow, fat, and peripheral blood
15
Q
induced pluripotent stem cells (iPSC)
A
- Adult differentiated somatic cells that have been genetically reprogrammed to a pluripotent embryonic stem cell
- Forced to express genes important for maintaining the defining properties of embryonic stem cells
- Not yet known if iPSCs and embryonic stem cells differ in clinically significant ways
16
Q
application of stem cells
A
cell therapy: cell replacement therapy: traumatic spinal cord injury, Parkinson’s disease, diabetes, heart disease, vision and hearing loss, burns, osteoarthritis
research: information about the complex events that occur during human development
identify how undifferentiated stem cells become differentiated
disease modelling
drug development: new medications could be tested for safety on differentiated cells generated from human pluripotent cell lines, safety and efficacy
17
Q
use of stem cells in regenerative medicine
A
Adult stem cells: Mainly for cell replacement therapies 1. Bone Marrow Stem Cells 2. Peripheral Blood stem cells 3. Umbilical Cord blood stem cells 4. Adipose tissue (fat) stem cells
18
Q
hematopoietic stem cell transplantation
A
- Bone marrow transplants: Medical procedure to replace defective bone marrow stem cells with healthy cells
- Derived from
o peripheral blood after stimulation of stem cell replication through growth factors
o bone marrow removed from a large bone of the donor (typically the pelvis) through a large needle - Replace stem cells that have been damaged by high doses of chemotherapy in patients with leukemia, lymphomas or myelomas, and certain solid tumors
1. Allogenic stem cell transplantation
2. Autologous stem cell therapy
19
Q
allogenic stem cell transplantation
A
- Donor and the recipient of the stem cells are different people
- Possibility of graft-versus-host disease = rejection of tissue which is “not self”
- Allogeneic HSC donors must have a Human Leukocyte Antigen (HLA) type that matches the recipient
- Transplant donors may be related or unrelated (National Marrow Donor Program)
- Even if there is a good match at these critical alleles, the recipient will require immunosuppressive medications
- Allogeneic transplants are also performed using umbilical cord blood as source of stem cells
20
Q
HLA - Human Leukocyte antigen
A
- HLA = Human Major Histocompatibility complex (MHC)
- HLA gene is located on chromosome 6p21.31
- HLA molecules are embedded into the cell surface
- Control the immune response through recognition of ‘self’ and ‘non-self’ by peptide presentation to immune cells
- HLA is its extremely polymorphic (variable)
- The better the match of HLA types, the higher the likelihood of a successful transplant
- Testing for HLA can be done in a laboratory by sequencing the DNA
21
Q
autologous stem cell therapy
A
- Donor –> Isolation of own stem cells –> reintroduction of own cells
- Harvested adult stem cells purified, assessed for quality and frozen
- Cells reintroduced in the donor/patient directly or after expansion of stem cells in the laboratory - “increasing the reserve” by transfusion
- E.g. to replace destroyed tissue and resume the patient’s normal blood cell production
- Stem cells come from the same patient –> there is no rejection
