✅ M2 - Stem cells Flashcards
What are the stages of pre-natal human development (pre-natal)?
- Pre-gastrulation:
Fertilisation -> Cleavage of zygote -> Uterine implanation -> Formation of primitive streak (body axes) - Post-Gastrulation: Gastrulation -> Neurogenesis -> Organogenesis
What happened during pre-gastrulation?
- Post-fertilisation of parents’ gametes
- Fertilized cells divided into more daughter cells called blastomere
- As the blastomere expands, forming the blastocyst with two cell types:
- Inner cell mass (ICM): embryo
- Trophoblast: extra-embryonic membranes, e.g. placenta - Uterine implanation:
- Driven by the trophoblast, to receive extra nutritions from blood supply.
- ICM expands and changes shape and location, but only one type of cell. - Formation of Primitive streak:
- Appear during gastrulation, due to thickening of the epiblast (upper layer of cells in the embryonic disc)
- Establishing body axes: A-P, D-V, L-R axes
- Why? Signals from the primitive streak help organise tissues along these axes.
What happens during gastrulation? (3 features)
- Establishment of the three primary germ layers: ectoderm, mesoderm, and endoderm
- Giving rises to different tissues and organs in the embryo.
- Mass cell division
- Cell migration to specliase
1. First migration → move to endoderm (inner layer)
2. Second migration → move to mesodorm (middle layer)
3. Final migration → move to ectodorm (outermost layer)
What happens post-gastrulation?
- Neurogenesis:
- Appears along the A-P axis: defining the framework
- Formation of somites -> creating future muscles and vertebral column, and dermis of the skin.
- During development, they provide landmarks along A-P for organ formation. - Organogenesis :
- By 56 days (first trimester), already have the defined shape of the fetus.
- Using the head to tail reference axis, other cells move, get more specialised and organised into tissues and organs.
What are the features of cell specialisation development?
- Cell potency (to transform to different types) gets progressively restricted as they become further specialised
- Those from zygote → adult cell have highest potency.
- Committed progenitor is determined: cell fate is locked (can only turn into that specialised cell)
=> Progenitor is adult stem cell type: can only differentiate within that particular group of organ
What are the types of cell and their potentials?
- Zygote: totipotent
- Blastocyst: pluripotent, self-renewing -> embryonic stem cell
- Adult: multipotent, self-renewing -> multipotent stem cell
- Organ cell
- phase 1: limited potential, limited renewal -> progenitor (choose between 2-6 cell fates only in particular tissues)
- phase 2: limited division -> committed progenitor (cell fate is locked)
- phase 3: no division functional -> differentiated
How can cells be differentiated? What leads to the differences between cells?
- The proteins present in that cell (cell ID) ⇒ depends on the genes it expresses
- Even though the full copy of the gene is present in ALL cells, depends on the cells, some genes are switched ON/OFF at some point → specialisation.
- 10% of these genes are developmental genes. Changes in the expression of these genes create differences amongst cells.
What are 2 features of stem cells and how it can become specialised?
- Two features:
- Can proliferate
- Can specialise - How it become specialised: through cell signaling
- Signals comes from neighbouring cells
- Encoded by developmental genes (since zygote)
- Leads to change in gene expression
=> Have the capacity to differentiate into a variety of more specialised cell types once it has received certain signals.
How is telomere relating to a cell’s proliferation capacity?
- What are telomeres?
- End parts of chromosomes
- Made of non-coding DNA repeats, to protect the chromosomes. - How does this relate to cell proliferation capacity?
- At each mitosis, several telomeric repeats do not get replicated.
- Telomeres get shorter => reducing the cell proliferative potential
- Cells expressing Telomerase (enzyme maintaining telomere’s length) can protect their telomeres -> levels of expression of Telomerase influences proliferation capacity.
What are the 2 types of stem cells found in humans and their features?
- Embryonic stem cells (ESCs)
- Immortal and pluripotent
- Location: blastocyst
- Can make any cells in the body - Adult/somatic stem cells (ASCs) - also found in children
- Present in many tissues, but cell-renewal rate issues insufficient to repair trauma
- Multipotent (lab grown shows plasticity)
- Location: brain, skin, bone marrow, skeletal muscle, epithelial (intestine) and fat cells
Why are stem cells from placenta/umbilical cord blood stem cells are better compared to ones found in bone marrow?
- Bone marrow contains hematopoietic SC (HSC) and mesenchymal SC (MSC), same as placenta/umbilical blood stem cells (neonatal)
- Why they are better than bone marrow:
- Less immunogenic (less likely to reject receiver)
- Longer telomeres (longer life)
- Less DNA damage (not expose to environment)
- Non-invasive harvesting (can collect naturally/from donation)
- Same plasticity (versatile)
Why immuno-compatibility in stem cell transplant is important & why neonatal cells are less immunogenic?
- Why important:
- Our own adult cells have surface proteins (ID card) so our immune system won’t attack them
- Encoded by 5 genes with several co-dominant alleles (5 maternal and 5 paternal proteins). - Risk that can happen during transplant: Graft-versus-host disease
- Donor immune cells accidentally transferred to recipients
- Donor’s immune cells attack host (recipient) own organs
=> Some level of tolerance, but limited. - Why neonatal cells are less immunogenic?
- Embryos and fetuses have to evade mother’s immune system (don’t have the ‘ID’).
- Less surface markers on cells -> Easier to match with recipient and less prone to rejection.
- New born babies do not have a mature immune system (no antibodies) -> less chance of graft-versus-host disease.
What are the currently approved and recent advancement in stem cell-based therapies and new advancement in stem-cell applications?
Current approved application:
1. Skin graft
2. HSC transplant to treat blood disorders
- From adult bone marrow or neonatal cells
- Collect HSC -> multiplied HSC in cell culture -> transplant to patients
Recent dvancements in stem cell-based therapies:
- Tissue engineering (e.g. MSC for cartilage engineering and recreation)
- MSCs are isolated (from bone marrow or neonatal)
- Tested in two ways (ex vivo or in situ)
Why are MSC useful in regeneration of cells? List a few (6) features
- Easy to isolate and grow in the lab
- Lab plasticity -> can specialise into cardiac muscles, skin and nerve cells.
- Can be frozen and thawed without apparent damage → potential for “off-the-shelf” therapy.
- Possess potent immuno-suppression and anti-inflammation effects (protective effects on local tissue), so capable of:
- homing (going to site of injury)
- stimulate regeneration (secrete repairing factors) - Could increase tolerance to find a donor match for MSCs transplant (immunosupressant to prevent immune system to attack)
- Potential treatment or complement to transplant for many diseases.
What are some problems with the hype about MSC transplants?
- May not have enough clinical tests
- Maybe false claims from clinics, no way to know the truth.
- Long clinical trial/testing time
- A lot of foreign clinics advertise treatments with MSCs or Umbilical cord cells. None of them have published data from clinical trials.
