A
A soft tissue inside the bone responsible for hematopoiesis
Long term cellular initiating assay; use of well plate with stromal feeder cells, maintain culture for 5-8 weeks, harvest cells and transfer to methylcellulose CFU-C cultures
LTCIC assay
Genomic alterations, epigenetics, metabolism, extrinsic factors, post-translational control; 6 fates include differentiation, cell death, proliferation, self-renewal, migration, quiescence
Determines HSC fate and their 6 fates of a HSC
Cytokines
Glycoprotein hormones that exist in soluble and/or membrane bound forms
Chronic myelogenous leukemia (CML); polycythemia vera (PV); essential thrombocythemia; primary myelofibrosis (PMF); chronic eosinophilic leukemia; chronic neutrophilic leukemia
6 chronic types of myeloproliferative neoplasms
Production of blood cells from dividing stem and progenitor cells
Hematopoiesis
Arrests cells in metaphase
Colcemid
Mediators of inflammation and guide for leukocytes; some chemokines crucial for stem cell mobilization and homing
Chemokine function
Several rodent species generate new batches of fertilized embryos while still pregnant-- new embryos arrest at blastocyst stage until uterus is vacated then implant and resume their development
Diapause phenomenon
Ionizing radiation, chemical exposure to benzene, treatment with chemotherapy agents i.e. topoisomerase inhibitors
Environmental risk factors-- leukemia
Disproved humoral system requirement for reconstitution of bone marrow; allowed further research into stem cells/transplantation for regeneration
Cellular Hypothesis
HOXB4
Wnt
Notch
Sonic Hedgehog
4 main pathways in HSC
1- defined anatomical site
2- a location where SCs could be maintained and reproduce
3- place where SC differentiation was inhibited
4- defined space that limited the number of SCs
4 basic concepts for stem cell niche
1998-- inner cell masses isolated from frozen-thawed donated human embryos by IVF; cultured and added to fibroblast medium showed undifferentiated morphology
Human embryonic stem cells (hESC)
Azurophilic granules, phaggot cell (multiple auer rods)
Peripheral smear of APL
B220 negative B cells
The first monoclonal antibody developed for identification of stem cell population in mice
LT-HSC (long term) --> ST-HSC (short term) --> MPP (splits into two separate pathways after multipotent progenitor) --> CMP & CLP (common myeloid progenitor & common lymphoid progenitor)
Hematopoiesis hierarchy
Suggested that SCs need to reside in bone marrow to retain their stemness
Schofield- stem cell niche
A composite of erythroid cells in the bone marrow that surrounds a central macrophage; erythroid niche
Erythroblastic island
ATRA (all trans retinoic acid) -- causes maturation of leukemia promyelocytes by dissociating fusion protein and promoting transcription
reduces tumor burden and risk of DIC
used with chemotherapy
Treatment of APL
Treatment of leukemia and other bone marrow related diseases; CML (chronic myelogenous leukemia) translocation of chrom. 9 & 22-- philadelphia chromosome
Practical use of HSCs
Their number correlates with amount of CFU-GM present and cells increase with use of growth factors and small dose chemotherapy.
Discovery of CD34+ in peripheral allowed for research into developing peripheral blood stem cell transplantation.
CD34+ cells found in the peripheral blood
Basement membrane contains both stem cells and niche cells to which they are bound-- the stem cell can reproduce as needed to make both new stem cells and progeny cells for specified differentiation
Basic model of stem cell niche
Present in areas of active hematopoiesis; produces basement membrane components of collagen and fibronectin, potential role in cytokine production and regulation in bone marrow
Importance of adipose cell in HSC niche
Bleeding from DIC
Main cause of induction mortality in APL first 7 days