L1. Haemopoiesis and Stem cells

Question 1

Where are the cells of haematopoietic tissue generated from and how does the location of haemopoiesis change from fetal to adult life.
How does myelofibrosis (blood cancer) affect this?

Answer 1

1. Generated from mesoderm in blood islands of the yolk sac (transient primitive cells)
2. Definitive cells come from endothelium in the aorta-gonad- mesonephros region
3. Haematopoiesis then shifts to the fetal liver
4. In fetal/neonatal life haemopoetic tissue is all bone marrow
5. During childhood it there is progressive replacement of marrow with fat, so haemopoeisis moves from long bones to only (50% of) axial skeleton in the adult
   - sternum, ribs, sacrum, and spleen which plays a minor role

Myelofibrosis causes expansion of haematopoeisis in long bones, spleen and liver - extramedullary haematopoeisis

Question 2

What are the 2 main components of the structure of bone marrow and how do they contribute to the haemopoietic stem cell (hsc) niche

Answer 2

1. Trabecular bone and hp tissue in variable quantities- no stratification of maturing hp cells
2. Bone marrow stromal cells (fibroblasts, macrophages, fat cells, endothelial cells) which provide structural support and microenvironment of ECM, adhesion molecules and blood cell growth factors needed to sustain hsc

Question 3

What are the steps in lineage from Haemopoeitic stem cell (hsc) to 7 final lines

Answer 3

1. HSC –> MultiPotent progenitor –>
2. a) Common Lymphoid progenitor –> B and T lymphocytes

2b) Common Myeloid progenitor–>
3a) Granulocyte/Macrophage colony forming unit –> granulocytes and macrophages separately
3b) Megakaryocyte/Erythrocyte progenitor -> RBC and Megakaryocyte separately
4. Megakaryocyte–> platelets

Question 4

Compare proliferative potential, turnover rate, number of cells and presence in blood of Mature cell populations and stem cell/progenitor populations

Answer 4

• Only the last cell population observed in significant numbers in blood. These have a higher turnover rate but lower proliferative potential compared to

Stem cell/progenitor populations (Earlier development of the lineage) stays in the bone with only small numbers of stem cells and progenitors present in circulating blood- less turnover

Question 5

What is the 3 sources of HSC for transplant

(bc of blood cancer, genetic disorders so need to repopulate the marrow with good stem cells from a donor or self before chemo/radiotherapy)

Answer 5

1. Peripheral blood which is run through a leukapheresis machine (after being stimulated by a hp GF like GCSF) which separates HSC and returns the other cells with the rest of the blood back into the person
2. Bone marrow liquid aspiration of 500-1000mL depending on donor and recipient habitus
3. Umbilical cord blood (60-70ml with less cells) good for pediatric transplant. Kept in cord blood banks.

Question 6

What is the marker of HSC , how many are there and what are two functions of HSC

Answer 6

HSC express CD34 antigen. Very small fraction of the total bone marrow/blood cell population
Two jobs: self renewal and generation of one or more specialised cell types

Question 7

What are the 2 things that regulate haematopoeisis :

Maintain homeostasis, produce the right amount, increase production in reaction to stress: infection & blood loss

Answer 7

1. Internally sourced: Transcription factors control normal maturation of blood cells
2. Externally sourced: Cytokines = Growth factors which can be lineage specific or general (acting early one) .

Question 8

What is EPO, TPO, G-CSF and their functions . Which is the only one not used clinically

Answer 8

EPO: erythropoeitin: stim RBC production

TPO: thrombopoeitin: stim platelet production (no longer in clinical use- now use TPO-ametics)

G-CSF: granulocyte colony stimulating factor: stimulates neutrophil production

Question 9

What are the main investigations of blood and bone marrow in clinical practice

Answer 9

1. Peripheral blood: Full Blood count/CBC- to see which populations are elevated.
   - Blood film can be examined for morphology if abnormal parameters
2. Bone marrow liquid aspiration from post. superior iliac crest for cytological examination of haematopoeitic cells
3. Bone marrow trephine produce a core biopsy for marrow architecture and cellullarity

Both done under gen anaesthetic and sedation

4. Stem cells can be assessed indirectly by colony assay and measurement of CD34 + cells