Flashcards in Hematopoiesis, Stem Cell Disorders Deck (32):
two defining characteristics of stem cells
self renewal and differentiation
germ cells. capable of differentiating into anything
has the ability to differentiate into multiple things
what is the potency of human stem cells?
example of totipotent cell?
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
example of stem cell division with two self renewing cells
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?
two types of marrow stroma niches
endosteal and perivascular
promotes quiescent self-renewal
promotes active differentiation
which cytokines regulate hematopoiesis?
interleukins (ILs) and colony stimulating factors (CSFs)
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
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
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
congenital stem cell defect in which there is a double stranded DNA repair defect. short stature, cancer predisposition, radial anomalies.
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
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
non-self HSC donor. HLA matched. used to replace faulty HSCs
graft vs host disease. donor t cell attacks host tissue