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Printable Handouts
Navigable Slide Index
- Introduction
- Differentiation pathways: granulopoiesis
- Granulopoiesis
- Granulocyte-colony stimulating factor (G-CSF)
- G-CSF restores neutrophil production
- Cytokines involved in granulopoiesis
- Differentiation pathways: erythropoiesis
- Erythropoiesis
- Erythropoietin (EPO)
- Downstream pathway of erythropoietin
- Erythropoietin response
- Erythropoietin accelerated RBC production
- Differentiation pathways: platelets generation
- Thrombopoietin
- Megakaryocyte
- Thrombopoietin and its receptor cMpl
- Downstream pathway of thrombopoietin
- TPO enhances time of platelet recovery
- Molecular basis of hematopoietic differentiation
- Challenges and opportunities in HSC expansion
- Cord blood CD34+ expansion assay
- Telomere length in long-term cell expansion
- Telomeres after repeated expansion-isolation
- Summary of CB CD34+ cell expansion assay
- Self-renewal probability of HSCs is age dependent
- Stroma can favour the expansion of stem cells
- Cellular expansion using serum-free medium
- Engraftment of HSCs in NOD/SCID mice
- Conclusions
- Incorporating knowledge of HSC regulation
- How do HSCs find their way to the bone marrow?
- Endothelium and expansion of HSC
- Bone marrow sinusoidal vascular network
- Bone marrow stem cells evolve into various cells
- Perivascular homing and bone marrow retention
- Imaging of bone marrow
- Osteoblasts reside in close vicinity of SECs
- Summary
Topics Covered
- Granulopoiesis
- Granulocyte-colony stimulating factor (G-CSF)
- Erythropoiesis
- Erythropoietin
- Thrombopoiesis
- Thrombopoietin
- Hematopoietic stem cell expansion: challenges and opportunities
- Telomerase (TERT+TR) expression & telomere length in long-term expansion cultures of umbilical cord blood CD 34+ cells
- Self-renewal probability of human hematopoietic stem cells is age dependent
- Hematopoietic stem cell expansion: challenges and opportunities
- The bone marrow sinusoidal vascular network
- Bone marrow stem cells evolve into various cells
- Perivascular homing and bone marrow retention of hematopoietic stem cells
- role of osteoblasts relative to SECs in stem cell homeostasis
Talk Citation
Moore, M. (2014, March 5). Hematopoietic stem cells and progenitor cells: their role in normal blood formation 2 [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 3, 2024, from https://doi.org/10.69645/WEXY6186.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Malcolm Moore has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Hematopoietic stem cells and progenitor cells: their role in normal blood formation 2
Published on March 5, 2014
45 min
A selection of talks on Cell Biology
Transcript
Please wait while the transcript is being prepared...
0:06
Now I'd like to just
take each pathway
and discuss what goes on as
you mature from the progenitor.
And we're showing here
the CFU-GM and its ability
to give rise under the influence
of G-CSF to granulocytes,
and under the influence
of M-CSF to monocytes.
0:34
Granulopoiesis takes about five
to seven days from the progenitor
stage to the production
of the mature polymorph
with its characteristic
segmented nucleus.
0:53
This is now to describe one of
the cytokines that's become very
important because
of its clinical use
as the granulocyte-colony
stimulating factor.
It selectively promotes the
generation of neutrophils
and it induces proliferation
and differentiation
of the myeloid progenitor cell.
It is required at every step throughout the differentiation lineage.
It's not just an initiator
of differentiation.
Differentiation requires it even at
the terminal stage of maturation.
And if the terminal
maturation does not occur,
cells can be generated that
are partially differentiated,
and they have completely
different properties.
They become myeloid derived
suppressor cells, which actually
behave as suppressors
of the immune system.
They inhibit T lymphocytes,
and they actually
favor the production of tumors.
They're the Darth Vaders, if you
will, of the hematopoietic system.
But if they're allowed to
differentiate completely
to neutrophils, the neutrophil
is a major protector of the body
against bacterial
infection, and it also
has very potent activities
in killing tumor cells.
It uses the same mechanism to
kill bacteria by throwing out
a net, comprised of its nuclear
DNA, to surround the bacterium
or the tumor cell and releasing its
granule content of toxic substances
and kill quite effectively.
When it does so, it dies and has
to be replaced by a new population
of neutrophils that
migrate to the site
of inflammation or the tumor site.
It has no effect on the
more primitive cells
outside the G-CSF
progenitor pathway.
But interestingly, if you give
G-CSF for a number of days,
it actually mobilizes,
from the bone marrow
into the peripheral blood,
hematopoietic stem cells.
The way it does this is it
actually crowds the bone marrow out
with differentiating
granulocyte cells.
And this crowding actually
results in pushing
out the stem cells from their niche.
So it's almost a
mechanical crowding out
process that results
in this mobilization,
together with some enzymes
that cleave certain tethering
molecules such as the integrins
and some of the bound cytokines.
So clinically, G-CSF has a major use
in stem cell harvesting, stem cell
mobilization to
transplantation purposes.
But its major use is to
prevent the decline,
or at least reduce the decline, in
neutrophils following chemotherapy
or radiation therapy in patients.
It is the decline and the
loss of neutrophils that
make patients very
susceptible to infection.
And there was a lot of morbidity
and mortality associated
with high-dose chemotherapy until
G-CSF came along and could be used
to greatly reduce the period of
neutropenia when a patient was very
susceptible to these
infectious events.
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