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Bone Marrow Microenvironment
October 20 Lecture
28
Immunology
Graduate
10/22/2011

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Term
what we do know about the bone marrow microenvironment
Definition
-bone marrow is the site of residence of hematopoietic stem cells, progenitor cells, and precursor cells, and that in a healthy individual only the terminal cells are released into the circulation in bulk.
Term
stem cells introduced into the bloodstread will _______ to the bone marrow, where they encounter specific stromal cells, extracellular matrix (ECM) components, and cytokines that direct their survival, attachment, and differentiation
Definition
home
Term
the bone marrow in the adult that is active in hematopoiesis is found in the:
Definition
long bones, iliac crests, and sternum
Term
Bone marrow consists of _____% fat cells and ____% of hematopoietic cells
Definition
50%
50%
Term
HSCs interact with ______ that line the bone, and _______ that line the vasculature, which includes central arterioles and venules.
Definition
osteoblasts

endothelial cells
Term
There are other __________ that produce ECM, cytokines, and adhesion molecules, and macrophages that clean up cellular debris
Definition
stromal cells
Term
Osteoblasts
Definition
provide cell-cell signals through physical contact
Term
endothelial cells
Definition
provide cell-cell signals that help cells home to the bone marrow
Term
macrophages
Definition
these eat improperly formed RBC's and extruded RBC nuclei
Term
Adipocytes
Definition
the function of these cells in not well understood inside the bone marrow but they could include energy production or insulation
Term
Do HSC's stay in the bone marrow forever?
Definition
NO
HSCs home (reside) in the bone marrow, but are not locked up there; they can go on little trips to other places and then come back to their home
Term
microenvironment
Definition
defined as the the place that is locally within a few cells/adjacent to a specific location
Term
it is possible that some of the ______ lining the bone are able to tell stem cells that they are running low in number/need to regenerate
Definition
osteoblasts
Term
What are all the different things bone marrow cells interact with?
Definition
-with bone
-with vasculature
-with stromal cells
-with each other
Term
another name for microenvironment
Definition
niche
Term
CXCR4- SDF-1 interaction
Definition
CXCR4 is a HSC receptor and SDF-1 (aka CXCL12) is a factor secreted by osteoblast that sticks onto the ECM. Both factors interact with one another and this is just one of many ways how HSC's and osteoblasts can communicate
Term
Details on how cell-cell interactions cause mobilization and homing for HSC's
Definition
1) GCSF mobilizes HSCs by causing release of proteolytic enzymes like elastase, cathepsin G, MMP2 and MMP9 from neutrophils
2) proteolytic enzymes from neutrophils inactivate SDF-1 by cleaving NH2 terminal signal sequence
3) (so HSCs are able to mobilize and freely go into vasculature)

3) after the proteolytic enzyme steps reverse (and SDF-1 is now free) CXCR4 and HSCs are chemoattracted to the highly SDF-1 expressing endosteal/stromal niche.
4) Presentation of ECM-tethered SDF-1 induces transendothelial migration and homing to the HSD niche much like a haptotactic molecular guidance system
(stem cells undergo homing)
Term
what are the different kinds of stromal cells?
Definition
-fibroblasts
-endothelial cells
-macrophages
-osteoblasts
-adipocytes
Term
fibroblasts
Definition
these secrete ECM
Term
endothelial cells
Definition
these cells express molecules like selectins, and allow stem cells to hit and then rool and egress through vasculature
Term
osteoblasts
Definition
these do receptor-ligand signaling (produce SDF-1)
Term
secreted ECM components
Definition
-collagen types I,III, and V
-syndecan-1
-perlecan
-fibronectin
-laminin
-biglycan
-decorin
Term
a biopsy lets you see __________ while aspirating lets you see __________
Definition
architecture of cells

individual cells
Term
the 3 ways to look at a cell/try to identify it
Definition
1) look at size of cell
2) observe the nucleus
3) observe the cytoplasm
Term
myeloblasts
Definition
are granulocyte precursors
Term
a band
Definition
the precursor of a neutrophil (has a bent nucleus that hasn't split fully yet)
Term
what we hope to do in future with HSCs
Definition
1) to try to get stem cells to leave bone marrow
2) how to grow bone marrow in a lab
3) how to make bone marrow stem cells differentiate along a particular lineage
4) use of bone marrow for regenerative medicine
Term
plasma cell
Definition
stains blue and has round nucleus (but it is pushed to the side because protein is being made in the center of the cell)
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