Stem cells, tissues, tissue injury

what is a stem cell

vital foundation to life; starts as a single cell; A SINGLE CELL THAT CAN REPLICATE ITSELF OR DIFFERENTIATE INTO MANY CELL TYPES

What can a stem cell do

replicate itself and differentiate into many cell types

stem cells are

undifferentiated/immature

how are stem cells distinguishable from other cells of the body

-undifferentiated/not specified

-able to self renew

-have the potential to differentiate

what can stem cells turn into

- daughter cells that remain stem cells

- differentiated cells

what is prodominate stem cell division type

asymmetric - maintains the stem cell pool that won’t differentiate and mature

what happens in asymmetric stem cell division

- stem cell

- progenitor cells

What is a progenitor cell?

daughter stem cell that goes off to differentiate

when does symmetric stem cell division occur

under times of stress when we need one specific type of stem cell

what happens in symmetric stem cell division

- two progenitor cells are made

- two stem cells are made

---> TWO IDENTICAL CELLS ARE MADE

when would you see symmetric stem cell replication

- when you have lost a lot of blood

What is stem cell differentiation

Process by which unspecialized stem cells give rise to specialized mature cells

what is the stem cell niche environment.

- provides nourishment, structural support, and protection

what encompases the stem cell niche

cellular components, secreted factors, ECM, and hypoxia/metabolism

Why are stem cells normally dormant

reduces mutation possiblity. it is a protective state supported by the niche factors.

what promotes stem cells to wake every few months

- THEIR NICHE

--> decrease or increase in growth factors/chemicals

--> theory about vacant niche spot exists, signaling cells to divide

what happens to the area where stem cell division is normally occuriing under stress

- extramedullary niches may form (in the LIVER, SPLEEN, LYMPH NODES)

Under extreme stress, where can we get more blood

extremedullary niche areas can form hematopoiesis

where does stem cell division normally take place

bone marrow

what are the stem cell types

- embryonic - blastocyst, puripotenet capability

adult stem cells - anything after the blastocyst

- pluripotent

- totipotent

how do we work around getting embryonic stem cells from blastocytes

induced pluripotent stem cells - genetically modified mature adult stem cells brought back to pluripotent state.

totipotent stem cells, where are they found?

cell with greatest differentiation potential; they give rise to every type of cell. during early embryonic development; have the potential to give rise to ALL cells including placents

outer cell mass of blastocyte

what stem cells can make the placenta

totipotent

What do totipotent cells differentiate into?

into the blastocyte

what does the outer layer of the blastocyte form

- placenta and other structures supporting fetal development

what does the inner cell mass make

- has pluripotent cells which form the germ layer

what can the pluripotent stem cell differentiate into

-essentially any type of cell other than the placenta

ectoderm develops into?

think outer stuff.

skin and nervous system, sensory organs (mouth, sinus, teeth)

what does the trophoblast form

placenta

What does the endoderm give rise to?

think insides.

digestive tract, lungs and respiratory tract, bladder

what does the mesoderm give rise to

“middle” between outer most ectoderm and most middle endoderm.

muscles, bones, blood/blood vessels, lymph tissue, cartilage

multipotent stem cells

stem cells that can become a limited number of types of tissues and cells in the body; still can become a lot of things but less differentiation potential than pluripotent

adult stem cells are

multipotent

what is the function of adult stem cells

stored in the body to maintain and repair/replace dead or damaged cells; make all cell types from the tissue they live in; can self-renew

mesenchymal stem cells create what?

BONE

bone marrow and skeletal stem cells that give rise to:

- osteoblasts/osteocytes

- chondrocytes

- adipocytes

- stromal cells

neural stem cells create what?

NERVOUS TISSUE

special cells in the nervous system that are capable of dividing to form new tissue, including new neurons

Where does hematopoiesis take place?

depends on where we are in life

after birth, in bone marrow. into adult hood, main sites are in vertebra, sternum, and ribs.

Where is bone marrow found in the bones specifically?

medullary cavity

describe the structure of bone marrow

- stroma: network of sinuses

- vasculature: arteries and capillaries

- innervation: myelinated and unmyelinated to amintain vessel tone

What is yellow marrow?

fat cells that replace the hematopoetic cells with age. found in bones that once made blood cells.

hands, feet, arms, legs

what cells function as the regulators of hematopoesis

endothelial cells

what cell is responsible for the network that cells rest upon?

adventitial reticular

what is the pre curosor to a RBC

reticulocyte

what is the pre cursor to a platelet

megakaryocyte

what does the lymphoid progenitor stem cell give rise to

lymphocyte

do we have more granulocytes or agranulocytes

granulocytes

what are the granulocytes

neutrophils, eosinophils, basophils

What are the agranulocytes?

lymphocytes and monocytes

what is the growth hormone for leukopoeisis

CSF

What do stem cell recipients undergo before a transplant?

chemo to kill their immune system and make room for the donor cells

what is EPO used to treat

anemias, associated with low epo levels

what reactions do granulocytes produce?

their inflammatory and allergic reactions

neutrophils

ACUTE INFECTION

- most common granulocyte

- enter tissues; triggered by infection or cytokines

- short half life; 6 hrs

- cause inflammation

- bind to integrin; attracted by selectins

- pass through capillary walls via diapedesis

- leave circulation via GI

eosinophils

- short half life

- PARASITIC INFECTIONS AND ALLERGY

- attracted by selectins, bind to integrins, and enter through diapedesis

- most abundant in GI, respiratory and urinary tracts

basophils

release histamine, involved in immediate hypersensitivity/allergic reactions

when would you give supplemental EPO

renal failure, chronic inflammation, myelodysplastic syndromes

when would you give TPO (thrombopoietin)

in immune thrombocytopenia

when would you give G-CSF

- drug induced neutropenia

- congenital disorders with low nuetrophil count

- to pt after chemotherapy

Thrombopoietin stimulates what

production of platelets

thrombocyte life span

10 days

where is thrombopoietin secreted

liver

what does TPO stimulate

megakaryocytes to fragment and release enucleated cells

what is the average half life for neutrophils

6 hrs

what are the key cells for acquired immunity

Lymphocytes

where do T cells form

Thymus

B cells form where

bone marrow

Where are the majority of t-cells and b-cells found

in lymph nodes and spleen

what is the life span of a monocyte

3 months

T cell life span as compared to B cells

B cells have shorter life

what are monocytes stimulated by

cytokines released from T lymphocytes

what are examples of tissue macrophages

- kupffer cells in liver

- pulmonary alveolar macrophages

- microglia in brain

characteristics/functions of neutrophils

- multilobed nucleus

- granules

- ingest and destroy microorganisms

- coordinate early inflammation

Basophil characteristics and function.

- become mast cells in tissue and release histamine

lymphocyte feature and function

- small cell with different morphology

- generate specific immune respone

- B lymphocyte become plasma cell

- T cells provide cell mediated immunity

erythrocyte life span

120 days

function of erythrocyte

transport oxygen

when is EPO released from the kidneys

when O2 is decreased

maturation of RBC in bone marrow depends on what

- iron

- vitamin B12

- folic acid

features of RBC

- decreased in size

- make hemoglobin

- no organelles

- no nucleus

what are the 4 main tissue types

muscle, epithelial, connective, nervous

epithelial characteristics

- avascular, rely on diffusion through basal layer.

regenerate quickly

- apical, basal surfaces.

closely attached to one another

epithelial functions

barrier, protection of underlying structures, absorption & secretion.

what is epithelial tissue derived from (ectoderm, endoderm, mesoderm?)

all 3 germ layers

Connective tissue components

collagen for tensile strength reticular, elastin

mechanism of cell atrophy

decreased protein synthesis and increased protein degredation in cells

physiologic and pathologic cell atrophy

physiologic: due to normal stressor (e.g. the size of the uterus after pregnancy)

pathologic: loss of blood/innervation, aging, decreased workload

hypoplasia

SMALLER AMOUNT OF CELLS

tissue that did not develop normally and is smaller than it should be

mechanism of atrophy

decrease in protein synthesis and increase in protein degradation

hyperplasia mechanism

MORE CELLS = MORE DIVISION HAPPENING

physiologic hyperplasia examples

breasts during pregnancy

endometrium thickening during menstrual cycle

liver growth post resection

pathologic hyperplasia examples

growth of adrenal gland due to ACTH (makes them bigger),

proliferation of endometrium due to prolonged estrogen stimulus

what cells dont undergo hyperplasia

myocytes of the heart or neurons

hypertrophy

increase of cell size due to increase in protein

physiologic hypertrophy

enlarged skeletal muscle with exercise (size of cells get bigger, number of cells don’t increase)

pathologic hypertrophy example

increase in heart size due to aortic stenosis

metaplasia

ONE CELL TYPE TO ANOTHER

change from one cell type to another cell type in abnormal location

metaplasia mechanism

cell at site cant handle new environmental thing so it converts to a different type

metaplasia example

barrett esophagus - stomach acid is irritating the esophageal epithelial cells so it transforms to a cell type that handles it better.

what is metaplasia caused by

chronic chemical or mechanical irritation

is metaplasia reversible

yes, if the stressor goes away.

if it persists: may cause neoplasm