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Year 1 > Hematopoiesis & Bone Marrow > Flashcards

Hematopoiesis & Bone Marrow Flashcards

1
Q

Hematopoiesis can be divided into these three subsections of blood cell production

A
  1. Granulopoiesis (WBCs)
  2. Erythropoiesis (RBCs)
  3. Megakaryopoiesis (platelets)
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2
Q

Terminal, differentiated, committed

A

Mature blood cells

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3
Q

What is the amount of bone marrow transplants a year in US?

A

4,500

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4
Q

6 important properties of HSCs

A
  1. Differentiate into blood and immune cells
  2. Can be isolated from blood (1/100,000 blood cells) or bone marrow (1/10,000 cells)
  3. Self renewable
  4. Can mobilize out of bone marrow
  5. Restore long term hematopoietic function
  6. Can do apoptosis
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5
Q

How many blood cells does the bone marrow produce a day?

A

500 billion

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6
Q

Multilineage maturation of HSC (6)

A
  1. WBC
  2. RBC
  3. Platelets
  4. Mast Cells
  5. Dendritic Cells (i.e. immune cells, langerhans)
  6. Osteoclasts
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7
Q

Percentage of HSC out of notal nucleated cells in bone marrow

A

<0.01% RARE

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8
Q

How are HSC identified?

A

By flow cytometry

-laser based technology, biomarker detection

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9
Q

5 important markers on HSC

A

CD34, Thy1, MDR-1, c-MPL, c-kit

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10
Q

glycoprotein involved in cell adhesion (marker)

A

CD34

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11
Q

Drug efflux pump

A

MDR (multi-drug resistant)

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12
Q

What are the 3 sources of HSCs?

A
  1. Bone Marrow
  2. Peripheral blood
  3. Umbilical cord
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13
Q

Where does hematopoiesis start?

A

Yolk sac

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14
Q

What arise from the mesoderm in the aortogonadal nodeand become HSCs?

A

Hemangioblasts

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15
Q

At 5 weeks this organ takes over and becomes the primary source of hematopoiesis

A

Liver

spleen supports

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16
Q

When does bone marrow become major hematopoietic organ?

A

Mid-fetal development (8 weeks)

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17
Q

In abnormal circumstances, where can hematopoiesis occur in the adult?

A

Spleen, will be huge

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18
Q

How many HSCs do we have?

A

20,000

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19
Q

How many times do HSCs divide?

A

18 times

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20
Q

1 stem cell produces X progenitor cells, which produce Y precuror cells, which produce Z terminal cells

A

X=10,000 progenitor Y=50,000 precursor Z=25,000 terminal cels

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21
Q

What type of division can Stem cells undergo?

A

Asymmetric: 1 stem cell and 1 progenitor (has new markers)

can also divide symmetrically

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22
Q

Two main progenitor branches

A

Myeloid progenitor (granulocyte precursor), lymphoid progenitor

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23
Q

Myeloid progenitors

A

CFU-GEMM–>CFU-GM (->myeloblasts, granulocytes, osteoclasts) and CFU-EMK
(->megakaryocytes and erythroblasts)

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24
Q

Order of differentiation

A

HSC>Progenitor>Precurror>Differentiation>

Particular, mature cell(terminal)

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25
Q 
Reconstitutes all hematopoiesis....?
Stem Cell:
Progenitor:
Precursor:
Mature Cell:
A

Stem Cell: Yes
Progenitor: No
Precursor: No
Mature Cell: No

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26
Q 
Self renewal...?
Stem Cell:
Progenitor:
Precursor:
Mature Cell:
A

Stem Cell: Yes
Progenitor: No
Precursor: No
Mature Cell: No

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27
Q 
Response to cytokines...?
Stem Cell:
Progenitor:
Precursor:
Mature Cell:
A

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

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28
Q

Which is the only form of cell that has drug efflux pump?

A

Stem cell; MDR

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29
Q

Why are bad stem cells difficult to treat?

A

They are resting in G0 or prolonged G1 phase, have drug efflux pump so can resist

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30
Q

In adults, where do stem cells in bone marrow of large flat bones spend most of their time?

A

Iliac bones (widest part of pelvis) and sternum

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31
Q

Most of “bone marrow” transplants are stem cells collected from

A

Peripheral blood, NOT bone marrow

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32
Q

Stem cell plasticity latest reports

A

Scientists have been able to induce bone marrow or HSCs to differentiate into other types of tissue

33
Q

What encases the bone marrow?

A

Cortical bone (transversed by trabecular)

34
Q

What is the meshwork of blood vessels in between the bone called?

A

Sinusoids

35
Q

How is the extracellular matrix maintained?

A

Reticulin fibers (reticular framework)

36
Q

These two ingredients provide a sponge-like netowkr to support stromal and hematopoietic cells

A

Fibers and matrix

37
Q

Where is yellow marrow found?

A

Medullary cavity of long bones

38
Q

Where is red marrow found?

1(5), 2(1)

A
  1. Flat bones (skull, sternum, ribs, vertebrae, pelvis)

2. Long bones (trabecular bone at epiphysis)

39
Q

List 5 important stromal cells

A
  1. Fibroblasts (produce fibers, collagens, ECM)
  2. Osteoblasts
  3. Adipocytes
  4. Endothelial cells (line sinuses, vessels)
  5. Macrophages (store iron)
40
Q

What is the CXCR-4 - SDF-1 interaction?

CXCR-4 = cytokine receptor type 4
SDF-1= Stromal derived factor
A

One example of how stroma/microenvironment interact with stem cell

Neutrophils secrete enzymes that inactivate SDF-1 located on osteoblasts, encourage HSC to be released from cozy little area and mobilize. Can harvest them

41
Q

What causes the release of enzymes from neutrophils in the CXC-R4 - SDF-1 interaction?
What enzymes are released?

A
  • G-CSF

- elastase, cathepsin G, MMP-2, MMP-9

42
Q

What produces SDF-1 and regulates its expression?

A

Osteoblasts (they secrete many cytokines and overall help to regulate hematopoietic environment)

43
Q

Endothelial cells (stromal) secrete what cytokine and express which adhesion molecules?

A

cytokine IL5; E-selectin adhesion molecule

44
Q

During differentiation, what do adipocytes express to promote hematopoiesis and influence osteogenesis?

A

Leptin, osteocalcin, increased prolactin receptors

45
Q

What are 4 secreted ECM components in the bone marrow?

A
  1. Proteoglycans
  2. Fibers
  3. Glycoproteins
  4. Other matrix proteins
46
Q

What types of collagens make up the fibers secreted in the bone marrow?

A

I, III, V

47
Q

What is difference between bone marrow aspiration and biopsy?

A

Aspiration-removes bone marrow fluid and cells through a needle put into bone. Usually done first
Biospy-removes bone with marrow inside

48
Q

What do cytokines play a role in? (list 4)

A
  1. Inflammation
  2. Infection
  3. Tumorigenesis
    * *4. Hematopoiesis
49
Q

The action of cytokines may be these 3 types of signaling

A

Autocrine, paracrine, endocrine

50
Q

These cytokine stimulate hematopoiesis (2)

A

Growth factors, colony-stimulating factors

51
Q

True or False: Bone marrow stromal cells are the only cells that control hematopoiesis

A

FALSE. T-lymphocytes, monocytes/macrophages, and many others. Bone marrow stromal are most important though. Mature blood cels can also produce cytokines, feeding back into signaling system

52
Q

How are cytokines polyfunctional?

A

Can affect proliferation, differentiation, functional activation/stimulation, survival

53
Q

True or False: Cytokines can be early-acting or late-acting

A

TRUE.

54
Q

What is physical make-up of cytokines and why is it important?

A

Glycoproteins, sugar part helps stabilize and increases their half life. Typically small, low molecular weight

55
Q

Cell secretes a cytokine that stimulates itself

A

Autocrine

56
Q

Cell secretes a cytokine that stimulates a nearby cell

A

Paracrine

57
Q

Cell secretes a cytokine that stimulates another cell elsewhere in body

A

Endocrine (acts like hormone)

58
Q

Hematopoietic cytokines can ave additive, synergistic and what other type of effect?

A

Antagonistic

59
Q

How do cytokines communicate with target cells?

A

By binding to specific receptors; interaction results in activation of signaling cascade

60
Q

What are two important properties that differentiate cytokines (endocrine) from hormones?

A
  • Cytokines are very potent at low concentrations, circulating levels are almost undetectable. 1000x increase during trauma or infection
  • Cytokines are made by many cell types throughout body
61
Q

Erythropoitin is made in what organ (and where specifically)?

A

Kidney, juxtatubular interstitial cells

62
Q

These transcription factors respond to changes in available oxygen, particularly a decrease in oxygen

A

HIP, hypoxia inducible factor

63
Q

EPO causes a number of events in signaling cascade, but in a very specific cell line. What step of differentiation contain receptors to communicate and recognize EPO? Be specific about step and specific cell name

A

RBC progenitors (under myeloid branch), CFU-EMK (leads to erythroblast/normoblast and then erythrocytes)

SELECTIVE INTERACTION WITH CYTOKINE AND CERTAIN CELLS

64
Q

Where is thrombopoietin made?

A

In liver (and minor in kidney and skeletal muscles)

65
Q

What is the main function of thrombopoitein?

A

Makes platelets (+some effect on HSC)

66
Q

Describe TPO feedback regulation

A

Platelets take up TPO via receptors and remove from circulation. If low platelet count, more TPO circulating and is a signal to tell precursors to make more platelets!

67
Q

How many platelets are made a day?

A

100 billion. 10-20% are in spleen

68
Q

Function of G-CSF

A

Increases neutrophil numbers and function

G-CSF can be given clinically, white blood cell count will increase, neutrophil count will explode.
Bone marrow responds to this exogenous insertion

69
Q

Function of GM-CSF

A

Increases neutrophil, monocyte, and eosinophil numbers and function

70
Q

What makes G-CSF, and where

A

Made by macrophages, fibroblasts, and endothelial cells. In all organs

71
Q

What makes GM-CSF

A

Made by stromal cells, endothelial cells, and T cells

72
Q

Neupogen is used clinically to mobilize HSC from bone marrow into blood for harvest. What is Neupogen an example of?

A

It’s a cytokine, an example of clinical uses of G- and GM-CSFs

Used in hematology oncology in bone marrow transplant

73
Q

How do enzymes released from neutrophil inactivate SDF-1 ?

A

Cleaves its NH2 terminal signal sequence

74
Q

This cytokine almost exclusively works way up at HSC level before differentiation

A

Stem Cell Factor

75
Q

c-Kit ligand, mast cell growth factor, and steel factor are all different names for which cytokine? Why does it have these different names?

A

Stem Cell Factor: stimulates HSCs
c-kit ligand: binds to c-kit receptors
Mast cell growth factor: stimulates growth of mast cells
Steel factor: steel locus, affects pigmentation (melanogenesis)

76
Q

In addition to playing an important role in hematopoiesis, SCF (stem cell factor cytokine) also affects what other developments? (3)

A

Gametogenesis, Melanogenesis, Mast cell development

77
Q

Stem cell factors have not been used clinically yet. What might they be used for in future?

A
  • mobilize stem cells from donors
  • use it to grow stem cells
  • use as tumor marker
  • block it as tumor therapy
  • use it to deliver toxins to leukemia stem cells
78
Q

Kidney failure wold be most likely to cause reduction of which cytokine and which cell type?

A

EPO, red blood cells (anemia)

79
Q

Ossobuco

A

bone marrow in the kitchen, SOUP. great with sprinkled coarse sea salt

Year 1 (48 decks)

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