Hematopoiesis, Stem Cell Disorders Flashcards
two defining characteristics of stem cells
self renewal and differentiation
totipotent
germ cells. capable of differentiating into anything
pluripotent
has the ability to differentiate into multiple things
what is the potency of human stem cells?
pluripotent
example of totipotent cell?
morula
normal stem cell division
1:1 balance, 1 self renewing daughter cell and 1 lineage specific daughter cell
example of stem cell division with two differentiated cells
aplastic anemia
example of stem cell division with two self renewing cells
leukemia
HSC division
rare cells with rare divisions. numbers remain constant throughout life
if stem cells don’t divide often, which cells have the tremendous replicative capacity?
lineage specific progenitor cells (i.e. myeloid/lymphoid progenitor cells)
what do hematopoietic SCs divide into?
common lymphoid or myeloid progenitors
what differentiates a progenitor cell from a stem cell?
progenitor cells divide a ton but don’t self renew
what is the general environment that provides growth stimulation to HSCs?
marrow stroma
two types of marrow stroma niches
endosteal and perivascular
endosteal niche
promotes quiescent self-renewal
perivascular niche
promotes active differentiation
which cytokines regulate hematopoiesis?
interleukins (ILs) and colony stimulating factors (CSFs)
GM-CSF (granulocyte/macrophage)
important CSFs for all cells of the myeloid lineage. stimulate differentiation, proliferation, and mobilization.
cytotoxic injury to stem cells
chemotherapy and radiation kill rapidly dividing, undifferentiated cells. cytopenias are therefore expected side effects
EPO (erythropoietin)
produced in the kidney and stimulates RBC production
Effects of aging on HSCs
lower regenerative capacity, move more to perivascular niche, increased peripheral mobilization, myeloid skewed differentiation, increased self renewal capacity
effects of aging on marrow
decreased cellularity (increased adiposity), impaired osteoclast/blast function, increased leukemias & anemias
aplastic anemia
bone marrow failure due to suppression or disappearance of multi potent progenitor cells. Leads to cytopenias with any combo of anemia, thrombocytopenia, neutro/leukopenia
causes of acquired aplastic anemia?
idiopathic (autoimmune, SC defects), cytotoxic injury (chemotherapy, radiation, drugs), viral (hep, CMV, EBV, varicella)
treatment for aplastic anemia?
immunosuppressive therapy (IST), if IST fails, then HSC transplantation
when would you treat aplastic anemia with HSC transplantation first?
if a pediatric patient has a matched sibling
fanconi anemia
congenital stem cell defect in which there is a double stranded DNA repair defect. short stature, cancer predisposition, radial anomalies.
dyskeratosis congenita
congential stem cell defect in which there is a telomerase defect leading to increased cell apoptosis, skin dyspigmentation, oral leukoplakia, hair/nail dystrophy. fast growing cells affected
autologous transplantation
high dose chemotherapy followed by stem cell rescue from patients own HSCs. GM-CSF mobilizes HSCs into periphery, they are then removed and replaced after chemo. can only be used to treat non-stem cell problems
allogeneic transplantation
non-self HSC donor. HLA matched. used to replace faulty HSCs
GVHD
graft vs host disease. donor t cell attacks host tissue
graft rejection
host t cell attacks donor HSCs
