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Flashcards in Stem cell therapy Deck (7)
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Stem cell overview

-SCs have the ability to self renew and differentiate
-Totipotent-> pluripotent-> multipotent
-2 major types: embryonic (ESCs) and adult (ASCs)
-ESCs are pluripotent and ASCs are multipotent
-While ESCs can be turned into any type of cell, ASCs can only be used to replace the type of cell that is the ASCs' tissue of origin
-ASCs cannot be grown indefinitely (where as ESCs can), but ASCs can be reprogrammed to behave like ESCs



-All ESCs are derived from the inner cell mass (ICM)
-ESCs have unlimited self-renewal capacity
-They are pluripotent and thus can generate all cell types
-Induced pluripotent stem cells (IPS) are ASCs that are reprogrammed to enter an ESC-like state by forcing the expression of 4 TFs: Oct4, Sox2, Klf4, c-Myc


Neural stem cells (NSCs)

-A type of ASC that can produce all 3 major CNS cell types: neurons, astrocytes, oligodendrocytes
-NSCs are mainly found in the sub ventricular zone of the LV and the dentate gyrus of the hippocampus
-NSCs can be derived from ESCs and IPS cells
-Fibroblasts can be converted to NSCs by expression of certain TFs


Therapeutic uses of NSCs

-Replacement of missing or damaged cells
-Therapeutic delivery of macromolecules, neuroprotection, drug therapy, stimulating repair
-Drug discovery via stem cell based disease models


Parkinson's disease (PD)

-Due to degeneration of dopaminergic neurons in the substantia nigra
-Possible to graft in dopaminergic neurons (NSCs) to the SN to improve PD symptoms
-These cells reinnervate the denervated striatum and restore dopamine release
-Results can be monitored by PET
-Problems encountered: lack of sufficient amounts of tissue, variability in outcome, troublesome dyskinesia after Tx


Spinal cord injury

-Delivery NSCs to spinal cord after injury can allow for cell replacement, trophic support of surviving cells, and axon regeneration
-Grafted cells secrete trophic factors that support growth of surviving cells and axon regeneration


Challenges facing NSC Rx

-Generating pure populations of NSCs that function like their in vivo counterparts
-Heterogenous differentiation of ESCs/IPS, no way to determine if these are functionally equivalent to in vivo counterparts
-Need to define a developmental stage of NSCs
-Improve survival and delivery of NSCs, also the connectivity/functionality of them
-Overcoming scar formation and utilizing endogenous signals that impact proliferation, migration, and differentiation of NSCs

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