9.0 BONE MARROW
Upon completion of this lecture, students will be able to:
a. Define and use properly the following words: Developmental Hemocytopoesis,
Yolk sac, Liver, Bone marrow, Extramedullary hemocytopoesis, Stem cell,
Pluripotential stem cells, Unipotential stem cells, Colony Forming Units (CFU),
Hematopoietic stem cell (HSC), Endosteal niche, Vascular niche, Multipotential
Progenitor cell (MPP), Lymphoid stem cells, Myeloid stem cells, Granulocyte
stem cells, Erythrocyte/megakaryocyte stem cells, Granulopoeisis,
Monocytopoiesis, Erythropoiesis, Nutrient Artery, Central longitudinal arteries,
Radial arteries, Sinusoids, Sinusoidal elements, Endothelial cell, Basement
membrane, Adventitial cell, Osteoclasts, Osteoblasts, Plasma cells, Mast cells.
b. Describe and associate basic structure/function for the following: 1) all structures
listed above; 2) stages of erythrocytic lineage maturation; 3) stages of
granulocytic lineage maturation.
c. Identify by microscopy the following cells, organelles, tissues: Red cell lineage;
White cell lineage; metarubricyte; reticulocyte; band cell; metamyelocyte;
megakaryocyte.
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BONE MARROW
I.
GENERAL INFORMATION
Bone marrow is a connective tissue responsible for the production of the blood cells. It is
located in the medullary cavities of bones. With age, bone marrow is limited to the proximal
epiphyses of long bones, vertebrae, sternum and skull. In mice and rats all medullary
spaces are hemopoetic throughout life.
II.
BLOOD CELL FORMATION
A. Video: Blood cell formation - University of Toronto
B. Developmental Hemocytopoetic sites:
1. week 2 - yolk sac
2. week 6 – liver
3. week 8 - bone marrow begins to form
4. 3rd month to 5th month - minor amount in spleen, thymus & other lymphoid
tissue
5. 5th month to adulthood - bone marrow primarily (long bone to flat bone)
C. Extramedullary hemocytopoesis
1. Spleen, liver, lymph node (under extreme demand)
2. With age, the long bone becomes less active and fills in with fat (yellow marrow)
but can be reactivated.
D. BLOOD CELL FORMATION THEORIES:
1. MONOPHYLETIC
a. A single STEM CELL that is PLUIPOTENTIAL (can differentiate into
many cell types)
b. gives rise to THE UNIPOTENTIAL STEM CELLS (cells committed to a
specific cell linage).
E. MAJOR BLOOD CELL TYPES
1. Red Blood Cells (RBC)
2. White Blood Cells (WBC)
a. mononuclear (agranulocytes)
b. polymorphonuclear (granulocytes)
3. Megakaryocytes
a. Platelets (thrombocytes)
F.
Environmental influences
1. Bone Marrow cells can enter blood under certain conditions:
a. Stress (due to release of glucocorticoids)
b. Anoxia
c. Toxemia
d. Bone marrow tumor
2. With an increase in the severity of condition, there is a greater increase toward
the progenitor Stem cell type to be released in to the blood
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III. STEM CELLS
A. General information
1. CFUs (Colony Forming Units) is derived from experimental data collected from
the injection of irradiated mice
2. Represents the stem cells of blood cell formation
B. Hematopoietic stem cell (HSC)
1. Endosteal niche
a. Long-term self-renewal
b. Some are quiescent and only respond to injury
c. Next to endosteal lining of bone-marrow cavities in trabecular long bone
d. Simulated by osteoblasts (and maybe osteoclasts)
2. Vascular niche
a. Hypothesis but strong supporting evidence
b. HSCs located next to sinusoidal endothelial cells
c. HSCs can move in and out of vasculature
3. Contribute to the formation of ‘Multipotential Progenitor cells’ MPPs
4. Cannot identify by routine light microscopy but have larger, euchromatic nuclei
C. Multipotential Progenitor cell (MPP)
1. These are the CFUs (such as CFU-L; CFU-GEMM)
2. Form the committed stem cells
a. Lymphoid stem cells
i. NK cells
ii. T-cells
iii. B-cells
b. Myeloid stem cells
i. Granulocyte stem cells
a. Neutrophilic; eosinophilic; basophilic
b. Monocytes
ii. Erythrocyte/megakaryocyte stem cells
a. Reticulocytes—erythrocyte (RBC)
b. Megakaryocyte—platelets
3. Cannot identify by routine light microscopy but have larger, euchromatic nuclei
D. Granulopoeisis
1. Stem cell – myeloblast – promyelocyte – myelocyte – metamyelocyte – band cell
a. Neutrophil
b. Eosinophil
c. Basophil
2. Look for myelocyte granules in cytoplasm
E. Monocytopoiesis
1. Stem cell – monoblast – promonocyte – monocyte – macrophage
2. Look for indentation of nucleus (although large lymphocytes in cow can be
indented)
3. Bluish-gray cytoplasm in monocyte
F. Erythropoiesis
1. Stem cell – rubriblast – prorubricyte – basophilic rubricyte – polychromatophilic
rubricyte—metarubricyte – reticulocytes – erythrocyte
2. polychromatophilic rubricytes no longer divide
3. 3-5 days to go from rubriblast to reticulocyte
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4. reticulocytes
a. grayish-pink cytoplasm (ribosomes)
b. no nucleus
c. 1-2 days in circulation, lose ribosomes
IV.
VASCULAR ARRANGEMENT OF BONE MARROW
A. Nutrient Artery (enters the long bone and penetrates cortical bone into bone marrow)
B. Central longitudinal arteries go up and down the bone
C. Radial arteries extend from the central arteries
D. arterioles enter osteons or exit and enter bone marrow and then empty into the sinusoids
E. Sinusoids open into the central longitudinal veins.
V.
FUNCTIONAL SIGNIFICANCE OF THE 3 SINUSOIDAL ELEMENTS
A. endothelial cell (specialized, non-fenestrated) is continuous but thin: has transient
apertures
B. basement membrane is discontinuous and easy passage for the new blood cells.
C. Adventitial cell is a reticular cell (fibroblast) that covers the surface of the endothelium
and forms a meshwork of reticulin as a filter.
VI.
OTHER CELL TYPES IN BONE MARROW
A.
B.
C.
D.
OSTEOCLASTS (multinucleated)
OSTEOBLASTS (eccentric nucleus and a central Golgi)
PLASMA CELLS
MAST CELLS
a. From MPP
b. Distinct from monocyte and granulocyte precursors
c. Purple granules; spherical nucleus
d. Throughout bone marrow
e. Routinely move into blood and then tissues
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