Topic 18 Stem Cells

Fertilized egg

divide to produce clone, self assemble into full organsim, Totipotency

Totipotency

Ability to form multicellular organsim, produce disteinct cell types, cell types express different set of genes

Tissue requirments

Mechanical strength - connective tissue, Delivery nutrients (oxygen) and removal waste - blood vessels, Electrical signaling - nerves, Disposal cell debris/combat infection - macrophage/lymphocytes

Tissue formation

cell made outside of cell, cells moved into tissue once made, some only made during development some continuously made

Stability of tissue

mixture of cells types, always being replaced, requires cell communication to monitor and react, selective cell adhesion to keep in place, cell memory to preserve identity (and pass down)

Tissue renewal rate

intestinal 3-6day, RBC 120days, Nerves never, Bones (osteoClast eats and osteoBlast makes), Skin 2 months, halted by ionizing radiation (radiation sickness)

Terminally differentiated

end of development, doesn’t divide, specialized cell, replace by proliferating precursors

Stem cells

self renewing, not differentiated, proliferate, in resident tissue, small amount, non descript (need molecular marker to find), developmentally restricted (specific set can differentiated into)

Cell replacement of intestine

single layer of absorptive/secretory cells, epithelial tissue into connective tissue (crypt), Stems cell at bottom of crypt, precursor move upward towards epithelial sheet (differentiate base what needed), tips of crypt die and shed into gut (digested)

Cell replacement of epidermis

stratified epithelium, stem cell stuck basal lamina, travel outward as differentiated, dead cells shed from skin surface

Hematopoiesis

stem cell in bone marrow, blood cell formation, new RBC/WBC/platelets

Stem cell control mechanims

made in correct location and amount, exchange extracellular signal (ex:Wnt protein)

Wnt proteins

signal molecule in intestine, promotes proliferation of stem cell, crypt secrete signal to prevent pathway outside, control cell diversification

Stem cell transfusion (mouse)

if all hematopoietic stem cell destroyed (bc cancer), bone marrow transplant for new stem cells, new hematopoietic cells

Pluripotene

proliderate indefinitely, unrestricted differentiation (can become any cell)

Embryonic stem cells (ES cells)

pluripotent, give rise all tissue/cells types, integrate into whatever site they occupy (adopt characteristic/behaviour)

mice ES cells

study gene function/organism development, genetic modification to inactive/modify genes, induce signaling molecule, differentiate in culture

Human ES cells

hyposthesis long rejected, use to as cell supply to replace/repair human tissue, immune rejection (destory if genetically different), Ethical? (human embryos used)

Induced Pluripotent Stem (iPS) cells

reprograme cell to ES state, expression Oct4/Sox2/Klf4, convert fibroblast cells, used for tissue formations (mice)

potential use of iPS

skeletal muscle for muscular dystrophy, Nerve cells for parkinson, Insulin secretiong for type 1 diabetics, Cardiac muscle for heart attack, grow whole organs for tansplants

current iPS cell uses

test potential effect of candidate drugs, produce cells of genetic disorder to be study, learn genetic disease mechanism, search for genetic disease treatment

Organoid formation

ES/iPS cell differentiate and self assemble, form 3D organoids

Organoid

miniature lab grown organs, ex: eye like structure (multicellluar retina), study organ development, identify/manipulate genes, explore cell interaction, study developmental pathways affect by disease, brain is most complex produced so far