Hematopoiesis & Bone Marrow Flashcards
Hematopoiesis can be divided into these three subsections of blood cell production
- Granulopoiesis (WBCs)
- Erythropoiesis (RBCs)
- Megakaryopoiesis (platelets)
Terminal, differentiated, committed
Mature blood cells
What is the amount of bone marrow transplants a year in US?
4,500
6 important properties of HSCs
- Differentiate into blood and immune cells
- Can be isolated from blood (1/100,000 blood cells) or bone marrow (1/10,000 cells)
- Self renewable
- Can mobilize out of bone marrow
- Restore long term hematopoietic function
- Can do apoptosis
How many blood cells does the bone marrow produce a day?
500 billion
Multilineage maturation of HSC (6)
- WBC
- RBC
- Platelets
- Mast Cells
- Dendritic Cells (i.e. immune cells, langerhans)
- Osteoclasts
Percentage of HSC out of notal nucleated cells in bone marrow
How are HSC identified?
By flow cytometry
-laser based technology, biomarker detection
5 important markers on HSC
CD34, Thy1, MDR-1, c-MPL, c-kit
glycoprotein involved in cell adhesion (marker)
CD34
Drug efflux pump
MDR (multi-drug resistant)
What are the 3 sources of HSCs?
- Bone Marrow
- Peripheral blood
- Umbilical cord
Where does hematopoiesis start?
Yolk sac
What arise from the mesoderm in the aortogonadal nodeand become HSCs?
Hemangioblasts
At 5 weeks this organ takes over and becomes the primary source of hematopoiesis
Liver
spleen supports
When does bone marrow become major hematopoietic organ?
Mid-fetal development (8 weeks)
In abnormal circumstances, where can hematopoiesis occur in the adult?
Spleen, will be huge
How many HSCs do we have?
20,000
How many times do HSCs divide?
18 times
1 stem cell produces X progenitor cells, which produce Y precuror cells, which produce Z terminal cells
X=10,000 progenitor Y=50,000 precursor Z=25,000 terminal cels
What type of division can Stem cells undergo?
Asymmetric: 1 stem cell and 1 progenitor (has new markers)
can also divide symmetrically
Two main progenitor branches
Myeloid progenitor (granulocyte precursor), lymphoid progenitor
Myeloid progenitors
CFU-GEMM–>CFU-GM (->myeloblasts, granulocytes, osteoclasts) and CFU-EMK
(->megakaryocytes and erythroblasts)
Order of differentiation
HSC>Progenitor>Precurror>Differentiation>
Particular, mature cell(terminal)
Reconstitutes all hematopoiesis....? Stem Cell: Progenitor: Precursor: Mature Cell:
Stem Cell: Yes
Progenitor: No
Precursor: No
Mature Cell: No
Self renewal...? Stem Cell: Progenitor: Precursor: Mature Cell:
Stem Cell: Yes
Progenitor: No
Precursor: No
Mature Cell: No
Response to cytokines...? Stem Cell: Progenitor: Precursor: Mature Cell:
Stem Cell: Yes, IL-3, SCF (Stem cell factor), TPO (thombopoietin)
Progenitor: Yes
Precursor: Yes, G-CSF, M-CSF, GM-CSF, EPO
Mature Cell: Yes, G-CSF, M-CSF, GM-CSF, EPO
G-CSF= granulocyte colony stimulating factor
M=macrophage
Which is the only form of cell that has drug efflux pump?
Stem cell; MDR
Why are bad stem cells difficult to treat?
They are resting in G0 or prolonged G1 phase, have drug efflux pump so can resist
In adults, where do stem cells in bone marrow of large flat bones spend most of their time?
Iliac bones (widest part of pelvis) and sternum
Most of “bone marrow” transplants are stem cells collected from
Peripheral blood, NOT bone marrow