Hematopoietic development PS ppt not mine

1. HEMATOPOIESIS
(Hematopoietic Development)

3. HEMATOPOIESIS
• Continuous regulated process of blood cell
production that includes cell renewal,
proliferation, differentiation and
maturation
• Process resulting in the formation,
development, and specialization of all of
the functional blood cells that are released
from the BM to the circulation

4. HEMATOPOIESIS DURING
FETAL DEVELOPMENT
Mesoblastic Period
Hepatic Period
Medullary Period

5. I. MESOBLASTIC PERIOD
(Yolk Sac Phase)
• Beginning of hematopoiesis
• Proginetor Cells migrate from
the AGM to the Yolk Sac
• Cells arising from the AGMR
give rise to HEMATOPOIETIC
STEM CELLS

6. I. MESOBLASTIC PERIOD
(Yolk Sac Phase)
• Primitive Cells Primitive Erythroblasts
• Remaining cells surrounding the cavity of
the yolk sac are called ANGIOBLASTS

7. I. MESOBLASTIC PERIOD
(Yolk Sac Phase)
• GLOBIN CHAINS produced:
– Epsilon (ε), Zeta (ζ)
– Embryonic Forms of Hgb
• Remain active only through the
8 – 12 week of gestation

9. II. HEPATIC PERIOD
• Cells are morphologically identifiable
• Lymphoid cells begin to appear
• LIVER – until the 1st to 2nd week of birth
• Fetal Liver : erythroid organ; minimal
production of lymphocyte and granulocytes
• Spleen, Thymus, Lymphnodes, Kidneys
• Detectable levels of HbF, HbA1 and HbA2

10. III. MEDULLARY PHASE
(Myeloid Phase)
• BM assumes the responsibility as the
main site of blood cell production
• M:E ratio approaches 3:1 by the 21
weeks AOG
• By the end of 6 mos, the BM becomes
the primary site of hematopoiesis
• Measurable levels of erythropoietin,
GCSF, GMCSF, HbF, adult Hb
• Various stages of maturation can be
seen in all cell lineages

11. POST PARTUM PHASE
• 3rd week: BM becomes the only normal site of
blood cell production and remains throughout
life
• 4th year of life : rate of BM growth exceeds the
need for blood cells
• 18 years : Active Hematopoietic sites are
limited to the pelvis, vertebrae, ribs, sternum,
and the proximal extremities of long bones

13. THE BONE MARROW

14. BONE MARROW
o Tissue located within the cavities of the
cortical bones.
o Types of Marrow :
o Red Marrow : found in the sternum, skull,
scapulae, vertebrae, ribs, pelvic bones, and
proximal ends of the long bones
o Yellow Marrow

16. • Venous Sinusoids : lined by endothelial
layer supported by intermittent fat cells and
adventitial cells
• Trilaminar Sinus : formed by the
endothelial cell, basement membrane, and
the adventitial cell

17. Primary blood cell formation occurs outside
the sinusoids in the hematopoietic cords,
which have an intimate relation with the
sinuses.
Mature red cells are capable of deforming to
enable them to pass through the narrow sieve
like apertures in the endothelial vascular
lining and enter the bone marrow sinuses and
circulation.

20. STEM CELLS

21. Background
• 1961: Till and McCulloch Study
• COLONY FORMING UNIT
SPLEEN (CFU – S) : referred to
as Committed Myeloid
Progenitors or CFU – GEMM

22. Morphological Divisions / Types
1. Noncommitted / Undifferentiated Stem
Cells
2. Multipotential and committed progenitor
cells

23. Theories of Hematopoietic
Progenitor Cell Origin
1. Monophyletic Theory : all
blood cells are derived from a
single progenitor cell
2. Polyphyletic Theory : each of
the blood lineages is derived
from its own unique stem cell

24. STEM CELLS
• Capable of self – renewal
• Give rise to differentiated progeny
• Able to reconstitute the hematopoietic
system of a lethally irradiated host

25. HEMATOPOIETIC STEM CELLS
• Limited in the bone marrow
• These are the cells, representing
various stages of maturation;
that occupy the normal bone
marrow

26. FATES OF the HSC’s
1. Self renewal
2. Differentiation
3. Apoptosis

27. Proposed Mechanisms of
Hematopoiesis
1. Stochastic Model ( Till and
McCulloch)
2. Instructive Model
Synthesis : The initial decision to self renew or
differentiate is probably stochastic, whereas
the lineage differentiation that occurs is
determined by various agents/signals from
the HIM in response to specific requirements
from the body.

28. The STEM CELLS
A. THSC : Embryonic Stem Cell
B. Pluripotential Stem Cells : Uncommitted
C. Culture Derived : Committed CFU’s (Adult Stem Cells
CFU – GEMM
CFU – E
CFU – Meg
CFU – M
CFU – GM
CFU – Baso
CFU – Eo
CFU – G
CFU – pre T
CFU – pre B

29. GENERAL FEATURES OF MATURATION
• NUCLEAR CHANGES
– Loss of nucleoli
– Decrease in size of the nucleus
– Condensation of Chromatin
– Possible change in shape of the nucleus
– Possible loss of the nucleus
• CYTOPLASMIC CHANGES
– Decrease in basophilia
– Increase in the proportion of cytoplasm
– Possible appearance of granules in the
cytoplasm

31. CYTOKINES AND GROWTH FACTORS

32. CYTOKINES
• Group of specific glycoproteins that regulate
the proliferation, differentiation, and
maturation of hematopoietic precursor cells
• Responsible for stimulation, or inhibition of
production, differentiation, and trafficking
of mature blood cells and their precursors.

33. GROWTH FACTORS
• Needed for growth and survival of
HSC
• Prevent hematopoietic precursor
cells from dying by inhibiting
apoptosis by stimulating them to
divide
• Regulate cell differentiation into
various cell lineages

34. COLONY STIMULATING FACTORS
• Produced by many different cells; have a
high specificity for their target cells and are
active at low concentrations
• Names indicate the predominant cell lines
that respond to their presence

35. INTERLEUKINS
• Numbered inorder in which they
were identified
• Characteristics:
– Proteins that exhibit multiple biologic
activities such as regulation of
autoimmune and inflammatory
reactions and hematopoiesis
– Synergistic interactions with other
cytokines and growth factors
– Interacting systems with amplification
potential
– Effective at very low concentrations